Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

Users Online : 46768

AbstractMaterial and MethodsResultsDiscussionConclusionReferencesDOI and Others
Article in PDF How to Cite Citation Manager Readers' Comments (0) Audio Visual Article Statistics Link to PUBMED Print this Article Send to a Friend
Advertisers Access Statistics Resources

Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"

Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018

Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."

Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018

Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."

Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018

Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."

Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
On Sep 2018

Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."

Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata

Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
On Aug 2018

Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".

Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
On Aug 2018

Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".

Dr. Mamta Gupta
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018

Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.

Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."

Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
On May 11,2011

Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."

Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
On April 2011

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.

Dr. Anuradha
On Jan 2020

Important Notice

Original article / research
Year : 2023 | Month : March | Volume : 17 | Issue : 3 | Page : AC01 - AC05 Full Version

Dose and Duration Dependent Effect of Fluoxetine on Dorsolateral Lobe of Prostate of Albino Rats-An Experimental Study

Published: March 1, 2023 | DOI:
Alka Aggarwal, SL Jethani, RK Rohatgi, Juhi Kalra

1. Associate Professor, Department of Anatomy, HIMS, SRHU, Dehradun, Uttarakhand, India. 2. Professor, Department of Anatomy, HIMS, SRHU, Dehradun, Uttarakhand, India. 3. Professor, Department of Anatomy, HIMS, SRHU, Dehradun, Uttarakhand, India. 4. Professor, Department of Pharmacology, HIMS, SRHU, Dehradun, Uttarakhand, India.

Correspondence Address :
Alka Aggarwal,
Associate Professor, Department of Anatomy, HIMS, SRHU, Dehradun, Uttarakhand, India.


Introduction: Fluoxetine is a prototype drug of the Selective Serotonin Reuptake Inhibitors (SSRIs) group of antidepressants. SSRIs help prostatic disease patients by improving life, decreasing the requirement of anti-inflammatory and antibiotic medication, decreasing the pain in the genital area, pain, and difficulty during urination, and improving urinary flow.

Aim: To investigate histological changes in the prostate (dorsolateral lobe) produced by different doses (10, 20 and 40 mg/kg/day) of fluoxetine given for different duration (Phases) in adult male albino rats.

Materials and Methods: An experimental study was done in the Anatomy Department, Himalayan Institute Medical Sciences (HIMS), Swami Rama Himalayan University, Jolly Grant, Dehradun, Uttarakhand, INDIA. The duration of the study was twelve months from May 2009-April 2010. Present study was done on 36 adult male albino rats divided into Control (Group 1) and Experimental (Group 2, 3 and 4). Rats respectively received 10 mg/kg/day, 20 mg/kg/day, and 40 mg/kg/day of fluoxetine Intraperitoneally (I/P) for phases of 2 weeks, 4 weeks, and 12 weeks. Prostate (dorsolateral lobe) tissue was collected, processed, and examined in a light microscope after Haematoxylin and Eosin (H&E) staining. Morphometric and statistical analysis (mean, standard deviation and student’s t-test) was done.

Results: Group 2 rats received fluoxetine for 12 weeks, Group 3 rats received fluoxetine for 4 weeks and 12 weeks, and Group 4 rats received fluoxetine for 7-10 days showed histological changes in the dorsolateral lobe of the prostate gland and stroma in the form of Smooth Muscle (SM) hypertrophy, epithelial cell changes (become cuboidal to flatten), epithelial cell degeneration, decreased diameter of the prostate acinus, and decrease in epithelial infoldings.

Conclusion: Fluoxetine (SSRI) alters the histology (both glandular acini as well as stroma) of the dorsolateral lobe of the prostate if used in low doses for a long duration, moderate doses for a few weeks and also for a long duration, and high dose for one week. This changed histology might be helpful in relieving the symptoms, pain, and discomfort felt by prostatic disease patients.


Benign prostatic hyperplasia, Prostatic carcinoma, Prostatic disease, Selective serotonin reuptake inhibitors, Testosterone

The Selective Serotonin Reuptake Inhibitors (SSRIs) are the most widely prescribed, relatively safe antidepressants used for many psychiatric illnesses (1),(2). Various clinical and animal studies showed that SSRIs not only influence sexual behavior but also change genital organ histology (3),(4),(5). Fluoxetine; the prototype drug of SSRIs significantly decreases Testosterone (T) levels (6). Clinical studies showed that fluoxetine improves the quality of life of men suffering from refractory chronic prostatitis by decreasing chronic genital pain, difficulty in micturition, and increasing urine flow (7). Fluoxetine also relieves symptoms of chronic pelvic pain syndrome. In elderly depressed patients with Benign Prostatic Hyperplasia (BPH), SSRIs improve quality of life by decreasing symptoms associated with BPH (8).

The prostate is the largest, highly specialized male accessory reproductive gland. It is a fibro-muscular-glandular organ surrounding the male urethra just beneath the urinary bladder (9). The prostatic fluid is rich in citric acid, zinc, proteins, protein-splitting enzymes, lipids, metal ions, calcium, sodium, potassium, and amines (10). McNeal divided the human prostate based on morphology and appearance into Peripheral Zone (PZ)-70%, Central Zone (CZ)-25%, and Transition Zone (TZ)-05% (11). The PZ is most prone to prostatic carcinoma (PCa) and TZ is most prone to BPH. The TZ lies near the prostatic urethra so any enlargement in this zone produces urinary symptoms (12).

Within the prostate 5-alpha-reductase (5-AR) metabolise T to more potent androgen Dihydrotestosterone (DHT). T and DHT are essential for the development, differentiation, proliferation, and survival of prostatic cells and play an important role in prostatic diseases (13). Prostate size and secretory functions depend on the T level. Prostatic involution/atrophy occurs rapidly on T withdrawal (bilateral orchidectomy/castration) and rapid reactivation of tissue growth occurs upon androgen replacement (14). In the healthy human male, up to 95% of T is derived from testicular Leydig cells. T levels fluctuate diurnally but remain highest in the morning. In most males after 50 years of age, a slow but highly variable decline in T levels is observed (15).

Middle aged males were found to suffer from prostate pathologies such as BPH and PCa which contribute to male morbidity and mortality. A study published in European Urology reported that men with unusually low amounts of T in their blood are 23% less likely to develop PCa. Scientists conducted a study on blood samples of 19,000 men aged 34-76 years collected between 1959 and 2004. They divided them into ten groups according to the lowest amount of blood T to those with the highest amount and compared their PCa risk. Of these men, 6900 went on to develop PCa. Men with the lowest levels of T were significantly less likely to develop PCa compared to all other men. In the metastatic stage of carcinoma prostate (PCa), androgen deprivation therapy has been used to inhibit androgen-dependent PCa and for symptom amelioration (16). Tamim HM et al., studied 7767 PCa patients diagnosed between 1981 and 2000 and found a positive significant association between the risk of PCa and Tricycle Antidepressants (TCA) but not found any positive association between PCa and SSRIs (17). Because of above mentioned clinical reports of relief in various painful symptoms of prostatic diseases after the Use of SSRI (7),(8) and there are no previous studies which evaluate the effect of fluoxetine on the histology of the prostate of albino rats. The Present study was done to determine the histological effect of different doses for different duration of fluoxetine on the dorsolateral lobe of the rat prostate.

Material and Methods

The present study was an experimental animal study. This study was done in the Anatomy Department, Himalayan Institute Medical Sciences (HIMS), Himalayan Institute and Hospital Trust (HIHT) University, Jolly Grant, Dehradun, Uttarakhand, INDIA. The duration of the study was twelve months from May 2009-April 2010. Approval from the Institutional Animal Ethical Committee (IAEC-(Registration No.589/02/a/CPCSEA) was obtained.

Study Procedure

The present study was done on 36 adult male albino rats; about 120-160 gm weight of Rattus norwegicus strain. These rats were obtained from the institutional central animal house. All the rats were housed in separate cages according to their groups. All the rats were healthy and disease/disability-free. Throughout the experiment, rats were fed on a standard balanced laboratory diet and water ad libitum with a 12-hour: 12-hour light-dark cycle; the water was changed and the cages were cleaned weekly.

The experimental drug was-Fluoxetine Hydrochloride-20 mg capsule (cap. Flunil-20 mg-INTAS Pharmaceuticals). The drug was injected once a day I/P according to the rat weight. 20 mg drug was dissolved in 2 mL of Normal Saline (NS) to obtain a concentration of 10 mg/ml. The drug was injected for 3 phases: 2 weeks, 4 weeks, and 12 weeks duration. Each phase consists of 12 animals which were further randomly subdivided into 4 groups of 3 albino rats each. Group 1 (Control)-received vehicle-NS, Group 2, Group 3, and Group 4 rats received I/P fluoxetine 10 mg/kg, 20 mg/kg, and 40 mg/kg of body weight/day respectively (18). For the calculation of drug dose and growth monitoring, all the rats were weighed on alternate days. At the end of each phase, the rats were sacrificed after giving ether anesthesia. Abdominal dissection was done immediately. Rats were infused with NS to wash out the blood. Prostatic tissues (dorsolateral lobe) were procured. Prostate tissue was fixed in 10% formalin. A 3-5 mm thick prostate tissue slices were taken and processed. A 4-5 μ thickness sections were obtained via microtome cutting. Cut sections were stained with Harris Haematoxylin & Eosin (H&E) stain. Histological examination and morphometric analysis of the dorsolateral lobe of the prostate were done under a light microscope with 20X magnification. Ten randomly selected fields were examined. Various features such as epithelial cell changes (cell number, cell height), degenerative changes, stromal changes, and SM changes were noted.

Statistical Analysis

The histological measurements were done with the help of an eyepiece micrometer. Mean, standard deviations (SD), and student’s t-test was calculated after data collection.


The initial mean age of rats was 13.2±5.66 weeks and the mean weight was 14.56±6.56 grams. The mean number of epithelial cells per 10 μm length and epithelial cell height per 10 μm length of the prostatic follicle/acinus epithelium was studied in the Group-1, Group-2, 3, and 4 albino rats of all three phases (2 weeks, 4 weeks and 12 weeks). The mean number of epithelial cells at the end of phases 1, 2, and 3 in Group-1 rats were 8.00±0.40, and 7.7±0.46 respectively; in Group-2 rats was 8.20±0.42, 7.90±0.30, and 8.00±0.00 (p=0.04) respectively; in Group-3 rats was 7.7±0.48 (p=0.04), 8.00±0.00, 8.00±0.00 (p=0.04) respectively; and in survived rats of Group-4 of phase 1 rats was 7.70±0.48 (p=0.04) (Table/Fig 1).

The mean cell height at the end of 2 weeks, 4 weeks, and 12 weeks in Group-1 rats was found 2.54±0.00 μm, 2.5±0.30 μm, and 2.3±0.40 μm, respectively; in Group-2 rats was 2.50±0.53 μm, 2.40±0.49 μm and 1.90±0.30 μm respectively; in Group-3 rats was 2.20±0.42 μm, 1.40±0.49 μm and 1.60±0.49 μm respectively; and survived rats of Group-4 of phase 1 was 1.20±0.42 μm (p=0.01) (Table/Fig 2), Group-3 rats prostate showed a decrease in cell height as the duration of drug exposure increased. Phase 2 and Phase 3 values were highly significant (p<0.01). The decrease in the cellular height may be due to degenerative changes in the cell.

In the present study, the Group-1 (Control) rats dorsolateral lobe prostatic tissue showed characteristic architecture; glandular acini are lined with secretory simple columnar epithelial cells with few epithelial infoldings. Detached epithelial cells present in the lumen within eosinophilic PS. Basal cells with stem cell characteristics (low nucleus-to-cytoplasmic ratio) have been identified in between secretory cells. A thin layer of circular SM surrounds the epithelium of glandular acini. In between the acini, there was a thin layer of fibromuscular stroma with blood vessels (Table/Fig 3).

The histopathology of the dorsolateral lobe of prostate of Group-2 phase 1, 2 and 3 are descriped in (Table/Fig 4),(Table/Fig 5),(Table/Fig 6). Group-2 (10 mg/kg/day) Phase 3 (12 weeks) rats dorsolateral lobe showing smaller prostatic acini with a decrease in epithelial cell height and a decrease in the secretory activity of epithelial cells. The epithelium showed proliferative changes in the form of hyperplasia, stratification, and the epithelial folds in the prostatic acini lumen. The SM layer surrounding these acini appeared thicker as compared with the SM layer surrounding the prostatic acini of Group-1 and Group-2 (Phase 1 and Phase 2). The prostatic nonmuscle Stroma (S) has a large volume in comparision to control and Group-2 phase 1 and phase 2. In the stroma, small caliber blood vessels were found.

The histopathology of the dorsolateral lobe of prostate of Group-2 phase 1, 2 and 3 are described in (Table/Fig 7),(Table/Fig 8),(Table/Fig 9). Group-3 (20 mg/kg/day) Phase 2 (4 weeks) rats dorsolateral lobe showed a highly significant decrease in epithelial cell height of glandular acini. DSC present in the lumen within eosinophilic PS. Glandular acini are surrounded by a very thin layer of Smooth Muscle (SM) fibers and widely separated by connective tissue stroma (Table/Fig 8). Group-3 (20 mg/kg/day) Phase 3 (12 weeks) rats dorsolateral lobe showed stratification of epithelium, decrease in epithelial cell height (significant), epithelial infolding in glandular acini (Table/Fig 9).

Very scanty prostate tissue was procured in survived rats of Group-4. Group-4 Phase-1 survived rats dorsolateral lobe showed an increased volume of fibromuscular stroma in between the prostatic glandular acini (G). Acini are smaller in size with few epithelial infoldings and surrounded by a thin layer of SM. In most places, acini are lined by simple squamous epithelial cells while in a few places acini are lined by simple cuboidal cells. DSC lies in the lumen within Prostatic Secretion (PS) (Table/Fig 10).


Present study, focused only on the dorsolateral lobe of the prostate histologic changes produced by fluoxetine. Price D studied the normal development of the prostate and seminal vesicle of the male albino rats at the University of Chicago and described different lobes (anterior lobe or coagulation gland, ventral lobe, paired lateral and dorsal lobe) of the prostate in rats (19). Hayashi N et al., studied morphogenesis and adult ductal branching patterns in the Sprague-Dawley rats prostate by microdissection method at the University of California, San Francisco, California, and found that each lobe has a unique ductal and acinar pattern although the epithelium of dorsal and lateral prostatic lobes more closely resembles each other; the so-considered dorsolateral lobe (20). Many investigators focused on one or two lobes of the rat prostate for their studies. The ventral lobe of the rat prostate has been preferred to see androgen action on the prostate (21). The dorsal and lateral lobes of the prostate have been preferred to see age-dependent prostatic hyperplasia (22).

Hayashi N et al., studied morphogenesis and adult ductal branching pattern in the Sprague-Dawley rats prostate by microdissection method at the University of California, San Francisco, California, and found that the dorsolateral lobe of the rat prostate has a ductal-acinar glandular structure with 5-7 pairs of main ducts. The dorsolateral lobe acinus has moderate to few epithelial infoldings and detached epithelial cells present in the eosinophilic secretion of the acinus lumen (20). In the present study, the control (Group-1) rats the dorsolateral lobe prostatic tissue showed the same acinar architecture.

In the present study, the dorsolateral lobe of the prostate showed changes on injecting low-dose fluoxetine for long period as well as high-dose fluoxetine for a few days in the form of shrinkage of the prostatic acini with epithelial changes (cells become cuboidal and flattened), atrophic changes in the prostatic acini epithelium (epithelial cells showed shrunken nuclei with condensed chromatin), and an increased stroma/gland ratio compared with controls. Moderate doses induce changes in the form of epithelial changes (cells become cuboidal) and atrophic changes of acini epithelial cells (pyknotic nucleus) with detached epithelial cells in the lumen. Stroma increased without shrinkage of acini. Liu R-F et al., studied the androgen effect on 40 healthy castrated Sprague-Dawley rat prostate histology and found that androgen administration inhibits apoptosis and induces prostate hyperplasia in the form of compacted glandular acini with thickened glandular epithelium with increased stromal cells (23).

Prostate epithelium and fibromuscular stroma depend upon androgenic hormones for their functional and structural integrity (24). Oliviera SM et al., (Brasil) studied 20 male adults (90-day-old) in Wistar rats, the effect of T on rat prostate tissue and found an increase in epithelial height with an increase in the secretory activity of epithelial cells in the form of increased eosinophilic secretion in the lumen. The epithelium showed proliferative characteristics, such as stratification and the presence of numerous epithelial folds in the prostatic lumen. Prostate acini were large and the muscular layer surrounding these acini appeared thinner as compared with the control. The prostatic stromal compartment was of large volume (25).

In the present study, as the dose of fluoxetine increased the glandular epithelium become flattened with pyknotic nuclei and increased stromal thickness. Low-dose fluoxetine administered for long period also showed attenuation of dorsolateral acini epithelium. These findings of the present study showed that the effect of fluoxetine was the opposite of the effect of androgen.

In the inhibition of pituitary hormones and gonadal steroids, prostatic atrophy occurs. A 5-AR enzyme (involved in the intraprostatic conversion of testosterone to its biologically active form dihydrotestosterone) inhibitors (finasteride and episteride) and antiandrogen substances (hydroxyflutamide) are known to induce prostate atrophy. Prostate atrophy grossly appears as glandular shrinkage and is microscopically seen as a reduction in the size of acini, attenuation (flattening) of lining epithelial cells, scanty secretory material in acini lumen, and increased stroma. Atrophy involves all lobes of the prostate (26). In the present study, scanty prostate tissue was procured from Group-4 survived rats and the same microscopic features were found.


The limitation of the present study was the lack of proper skill of dissection to procure the whole tissue of the prostate of the albino rat.


Present study showed that fluoxetine in mild doses for a long duration, moderate doses within a few weeks, and high doses within a few days alters prostate histology. The present study findings provide a rationale for further investigations on microdissected prostate to see the fluoxetine-induced histological and morphometric changes in the prostate. These studies may establish fluoxetine’s effect on prostate pathologies such as PCa and BPH.


Mottram P, Wilson K, Strobi J. Antidepressants for depressed elderly. Cochrane Database Syst Rev. 2006;2006(1):CD003491. [crossref] [PubMed]
Depression in children and young people: identification and management. NICE guideline [NG134]. 25 June 2019.
Depression in children and young people: identification and management. NICE guideline [NG134]. 2019. Available at: https:/
Santra R, Raychaudhuri P, Bagchi C, Tripathi SK. Chronic fluoxetine treatment and sexual behaviour in male and female albino rats. Indian Journal of Pharmacology. 2013;45(4):412-14. [crossref] [PubMed]
Balon R. SSRI-associated sexual dysfunction. Am J Psychiatry. 2006;163:1504-09. [crossref] [PubMed]
Soliman ME, Mahmoud BL, Kefafy MA, Yassien RI, El-Roughy ESA. Effect of antidepressant drug (fluoxetine) on the testes of adult male albino rats and the possible protective role of omega-3. Menoufia Medical Journal. 2017;30(4):1135-42. [crossref]
Karim KM, Gholamali EJ, Habibollah N, Shahram A. The effects of fluoxetine usage on the concentration of testosterone hormone. J Pharm Biomed Sci. 2012;2(7):87-93.>
Xia D, Wang P, Chen J, Wang S, Jiang H. Fluoxetine ameliorates symptoms of refractory chronic prostatitis/chronic pelvic pain syndrome. Chin Med J (Engl). 2011;124(14):2158-61.
Ma L, Zhu H, Yang W, Qian Y, Wang J, Feng M, et al. Antidepression medication improves quality of life in elderly patients with benign prostatic hyperplasia and depression. Int J Clin Exp Med. 2015;8(3):4031-37.
Lee CH, Akin-oluhbade O, Kirschenbaum A. Overview of prostate anatomy, histology, and pathology. Endocrinol Metab Clin. North Am. 2011;40:565-75. [crossref] [PubMed]
McNeal JE. Normal histology of prostate gland. Am J Surg Pathol. 1988;12:619-33. [crossref] [PubMed]
McNeal JE. The prostate gland: morphology and pathophysiology. Monograph Urol. 1988;9:36-63.
Kjoseland O, Tveter KJ, Attramadal A, Hansson V, Haugen HN, Mathisen W. Metabolism of testosterone in the human prostate and seminal vesicles. Scand J Urol Nephrol. 1977;11(1):01-06. [crossref] [PubMed]
Lee C. Physiology of castration-induced regression in rat prostate. In: Murphy GP, Sandberg AA, Karr JP (eds) The Prostatic cell: structure and function, part A: morphologic, secretory, and biochemical aspects. Liss, New York. 1981. Pp.145-59.
Ekman P. The prostate as an endocrine organ: androgens and estrogens. The prostate Supplement. 2000;10:14-18. 3.0.CO;2-7>[crossref] [PubMed]
Low testosterone levels are linked to reduced risk of prostate cancer. Nuffield Department of Population Health, Oxford University. 2018. Available at: https://
Tamim HM, Mahmud S, Hanley JA, Boivin JF, Stang MR, Collet JP. Antidepressants and risk of prostate cancer: a nested case-control study. Prostate Cancer Prostatic Dis. 2008;11(1):53-60. [crossref] [PubMed]
Silva JVA, Lins AMJAA, Amorim JAA, Pinto CF, Deiró TBJ, Oliveira JRM, et al. Neonatal administration of fluoxetine decreased final sertoli cell number in Wistar rats. Int J Morphol. 2008;26:51-62. [crossref]
Price D. Normal development of the prostate and seminal vesicles of the rat with a study of experimental postnatal modifications. Am J Anat. 1936;60:79-127. [crossref]
Hayashi N, Sugimura Y, Kawamura J, Donjacour AA, Gerad R. Morphological and functional heterogenicity in the rat prostatic gland. Biology of Reproduction. 1991;45:308-21. [crossref] [PubMed]
Hernandez ME, Soto-Cid A, Aranda-Abreu GE, Diaz R, Rojas F, Garcia LI, et al. A study of the prostate, androgens, and sexual activity of male rats. Reprod Biol Endocrinol. 2007;5:11. [crossref] [PubMed]
Banerjee PP, Banerjee S, Dorsey R, Zirkin BR, Brown TR. Age-and lobe- specific responses of the Brown Norway rat prostate to androgen. Biology of Reproduction. 1994;51:675-84. [crossref] [PubMed]
Liu RF, Fu G, Li J, Yang YF, Wang XG, Bai PD, et al. Roles of autophagy in androgen-induced benign prostatic hyperplasia in castrated rats. Experimental and Therapeutic Medicine. 2018;15:2703-10. [crossref] [PubMed]
Lee C. Physiology of castration-induced regression in rat prostate. In: Murphy GP, Sandberg AA, Karr JP (eds) The Prostatic cell: structure and function, part A: morphologic, secretory, and biochemical aspects. Liss, New York, 145-159.
Oliveira SM, Silva LS, Ledesma RHC, Silva RG. Histological analysis of rat prostate under exogenous testosterone and a low dose of oral selenium administration. Journal Health NPEPS. 2018;3(2):380-91. [crossref]
Gao W, Jeffrey DK, Vipin AN, Kiwon C, Parlow AF, Duane DM, et al. Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5α-reductase inhibitor finasteride, and the antiandrogen hydoxyflutamide in intact rats: new approach for benign prostate hyperplasia. Endocrinology. 2004;145(12):5420-28. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2023/62081.17571

Date of Submission: Dec 09, 2022
Date of Peer Review: Jan 09, 2023
Date of Acceptance: Feb 17, 2023
Date of Publishing: Mar 01, 2023

• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. No

• Plagiarism X-checker: Dec 17, 2022
• Manual Googling: Jan 28, 2023
• iThenticate Software: Feb 08, 2023 (11%)

ETYMOLOGY: Author Origin

JCDR is now Monthly and more widely Indexed .
  • Emerging Sources Citation Index (Web of Science, thomsonreuters)
  • Index Copernicus ICV 2017: 134.54
  • Academic Search Complete Database
  • Directory of Open Access Journals (DOAJ)
  • Embase
  • EBSCOhost
  • Google Scholar
  • HINARI Access to Research in Health Programme
  • Indian Science Abstracts (ISA)
  • Journal seek Database
  • Google
  • Popline (reproductive health literature)