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

Users Online : 35441

AbstractMaterial and MethodsResultsDiscussionReferencesDOI 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
Lucknow
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,
Muzaffarnagar.
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,
Bengaluru.
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
Consultant
(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)
E-mail: drrajendrak1@rediffmail.com
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.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

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
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Experimental Research
Year : 2012 | Month : May | Volume : 6 | Issue : 3 | Page : 542 - 546 Full Version

Effect of the Aqueous Extract of Mentha Arvensis on Haloperidol Induced Catalepsy in Albino Mice


Published: May 1, 2012 | DOI: https://doi.org/10.7860/JCDR/2012/.1958
MD. Parwez Ahmad, Hussain Arshad, Najmi Abul Kalam, Manocha Anshu, Akhtar Md. Hasin, Wahab Shadma

1. Ph.D Scholar, Faculty of Pharmacy, Integral University, Lucknow. 2. Associate Prof. & Head, Faculty of Pharmacy, Integral University, Lucknow. 3. Lecturer Department. of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi. 4. Lecturer Department. of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi. 5. Prof. & Head, Departmentt.of Pharmacolgy, National Medical College and Teaching Hospital, Birgunj, Nepal. 6. Ph.D. Scholar, Faculty of Pharmacy, Integral University, Lucknow.

Correspondence Address :
Md. Parwez Ahmad, Ph.D. Scholar
Faculty of Pharmacy
Integral University, Lucknow-226026
Mobile: 09473291002
E-mail: parwezmedicine@gmail.com

Abstract

Neuroleptic drugs (D2 blockers) which are used for the treatment of psychotic disorders, especially for schizophrenia, are known to produce extra-pyramidal side effects (EPS). Catalepsy was induced by these drugs in animals and these animals have been used as models to study the extra-pyramidal side effects which are associated with anti-psychotic agents in human beings. In the present study, we found out the protective effect of the aqueous extract of Mentha arvensis (MA) on haloperidol (2.0 mg/kg po administration) induced catalepsy in mice, by employing the standard bar test and the assessment of the locomotor activity. The mice were allocated to six groups, with each group containing seven animals. The effects of the test drug MA (500 and 1000mg/kg doses) and the standard drug, trihexyphenidyl (0.1mg/kg) were assessed after their repeated dose administration in mice for fourteen days, 30 minutes prior to the administration of haloperidol. The mice were sacrificed on the fourteenth day and the TBARS, glutathione, SOD and the catalase activities in their brain tissues were estimated by using the Ohkawa et al., Sedlak and Lindsay, Clairbone, Marklund and Marklund respectively. A significant (P<0.001) reduction in the cataleptic scores was observed in the test drug treated groups as compared to the toxic control, with a maximum reduction in the group with a drug dose of 1000 mg/kg. Similarly, our study suggested that MA had significantly reduced othe xidative stress and the cataleptic score which was induced by haloperidol. Hence, it could be used to prevent the drug- induced extrapyramidal side effects.

Keywords

Catalepsy; Anti-oxidant; Parkinson’s disease; Haloperidol; Mentha arvensis

Introduction
Worldwide, researchers have come to know that catalepsy does not appear of its own accord; instead, that it often manifests as a one in a constellation of the symptoms which are caused by psychotic disorders. Nowadays, the usage of typical anti-psychotic drugs has been limited because of the side effects and the toxicity which are produced by them (1). Haloperidol is a widely and commonly prescribed typical anti-psychotic drug which is used for the treatment of schizophrenia and other effective disorders (2),(3). Receptor binding studies have shown that haloperidol was equivalent to fluphenazine and that it was about twice as active as chlorpromazine, as an inhibitor of the binding of dopamine to the dopamine receptor. It has a high affinity for the dopamine D2 receptors and it acts by blocking them (1). But, haloperidol causes movement disorders such as the narcoleptics malignant syndrome, dystonias and tardive dyskinaesias (1). Oxidative stress, which is a culprit in many human diseases, has been implicated in haloperidol toxicity (4). Extra pyramidal symptoms (EPSs), including pseudoparkinsonism, occur as distressing side effects in 20-75% of the patients who are administered typical anti-psychotics (5). The blockade on the dopamine receptor which is caused by haloperidol increases the dopamine turnover in humans and rats (6). It has been proposed that haloperidol induced oxidative stress arises from the generation of free radical catecholamine metabolism by monoamine oxidases (MAOs) (7). The acute (8) and chronic (9) administration of haloperidol in mice resulted in the generation of significant oxidative stress in their brain regions, as was evidenced by loss of the nonprotein thiol anti-oxidant glutathione (GSH) and by the increase of the lipid peroxidation product, malonaldehyde. Original Article Dentistry Section The brain system is highly susceptible to oxidative damage (10) as it is enriched with the more easily peroxidable fatty acids and as it is not particularly enriched with the anti-oxidant defenses. Newer approaches which are used to treat the oxidative damage in the brain like Mentha arvensis, have anti-oxidant potential (11). Since haloperidol induced catalepsy has an underlying pathology of increased oxidative stress, the present study was designed to evaluate the effect of Mentha arvensis on haloperidol induced catalepsy. Trihexyphenidyl HCl was used as a standard drug (12). Mentha arvensis belongs to the family, Lamiaceae, which is popularly known as pudina, which is a common household remedy that has found its use in the Indian indigenous system of medicine against several ailments as an anaesthetic, anti-phlogistic, antidepressant, anti-microbal (13), antiseptic, anti-spasmodic, carminative, digestive, expectorant, nervine, stomachic, tonic and anti-fertility drug (14). It has beta-galactosidase activity (15) and it protects against radiation-induced lethality (16). It contains menthol (66%), (-)-menthyl acetate (15%) and (-)-menthone (8%) and it also has some phenolic content.

Material and Methods

Animal
Eight week old Swiss albino mice (weighing 20–30 g) which were obtained from the central animal house, Jamia Hamdard, New Delhi, India, were used in the study. The animals were housed under standard 12hr: 12hr light/dark cycles and were provided with food and water ad libitum. The animals were acclimatized to the laboratory conditions before testing them. Each animal was used once. The experiments were performed between 10.00 and 16.00hrs.The studies was approved by the institutionl ethical committee of Jamia Hamdard and the study was conducted according to the Indian National Science Academy Guidelines for the use and care of experimental animals.
Drugs and Dosage
Mentha arvensis was the test drug which was used. It was collected locally and it was identified by a botanist, Dr. M.P. Sharma, Professor, Department of Botany, Faculty of Science, Hamdard University, New Delhi-62. The Mentha arvensis was extracted with double distilled water. The extract which was thus obtained was vacuum evaporated in order to make it into powder form for it to be redissolved in double distilled water. It was stored in air tight containers which were protected from light. Trihexyphenidyl HCl (Wyeth Limited, Goa) and haloperidol (RPG Life Science Ltd. Ankleshwar) were suspended/ dissolved in 1% carboxy methyl cellulose solution. The treatments which were received by each group (each group consisted of seven animals, n=7) are shown in [Table/Fig-1]. The group which received normal saline (10ml/kg) served as the control group. The normal saline, trihexphenidyl Hcl (0.1mg/kg), MA (500 and 1000 mg/kg) (17), and haloperidol (2 mg/ kg) were given orally.
Experimental Design
Haloperidol Induced Catalepsy (HIC): Catalepsy was induced with haloperidol (2.0 mg/kg p.o.) and it was assessed at by means of a standard bar test and by the assessment of the locomotor activity on every fourth, eighth and fourteenth day of the drug treatment, as shown in (Table/Fig 2) (18), (19). The catalepsy was assessed in terms of the time for which the mouse maintained an imposed position with both the front limbs extended and resting on a 4 cm high wooden bar (1.0cm diameter). The end point of the catalepsy was considered to occur when both the front paws were removed from the bar or if the animal moved its head in an exploratory manner. A cut-off time of 300 seconds was applied. Between the determinations, the animals were returned to their individual home cages. All the observations were made between 10.00 and 16.00 hrs in a quiet room at 23-25Âş C.
Scoring Method
If the animal maintained the imposed posture for at least 20 seconds, it was considered to be cataleptic and the time was recorded in seconds. The animals were tested on every fourth, eighth and fourteenth day of the drug treatment and only the greater duration of the immobility was considered.
Assement of Locomotor Activity
Photoactometer test:
This test measures the exploration and the voluntary locomotion within an enclosed area. The objective value for the spontaneous motor activity was obtained by using a photoactometer (Techno electronics, Lucknow, India). The mice were placed individually in a 30 Ă— 30 cm black metal chamber with a screen floor and a light-tight lid. Six beams of red light were focused 2 cm above the floor in to photocells on the opposite side. Each beam interruption was registered as an event on the external counter. The floor of the chamber was wiped clean with a damp towel before each use. The mice were placed in the chamber one hour after the oral administration of the drug. They were allowed to acclimate for 2 min, and then the light beam breaks were counted for the next 10 min (19). In this study, MA was administered once daily, 30 min prior to the haloperidol administration, for fourteen days. Catalepsy was determined 30 min after the haloperidol administration on the fourth, eighth and on the fourteen day of the drug treatment. The animals were then sacrificed by cervical dislocation and the TBARS, glutathione, catalase and SOD (20),(21),(22),(23) activities of their whole brain tissue were estimated by using the Ohkawa et al.,(20) Sedlak and Lindsay, Clairbone, Marklund and Marklund respectively.
Assay of TBARS
Lipid peroxidation is a free radical mediated event. The primary products of such a damage are a complex mixture of peroxides which then breakdown to produce carbonyl compounds. The malondialdehyde (MDA) is one such carbonyl compound, which forms a characteristic chromogenic adduct with two molecules of TBA. The colourimetric reaction of TBA with MDA, a secondary product of lipid peroxidation, has been widely accepted for measuring lipid peroxidation. The total protein which was present in the homogenate was estimated by following the method which was described by Lowry et al (24). The units of the TBARS activity which were determined, were expressed in terms of nmoles MDA/ mg protein (20).
Assay of Glutathione
This spectrophotometric procedure was based on the method of Ellman i.e. DTNB [5, 5'-dithiobis-(2-nitrobenzoic acid)] is reduced by –SH groups to form one mole of 2-nitro-5- mercaptobenzoic acid per mole of –SH, as described by Sedlak and Lindsay. The units of the GSH activity which were determined were expressed in terms of nmoles μg/mg protein (21).
Assay of SOD
The assay of SOD was carried out, based on the ability of the enzyme to inhibit the auto-oxidation of pyrogallol, as described by Marklund and Marklund. The total protein which was present in the homogenate was estimated by following the method which was described by Lowry et al (24) . The units of the SOD activity which were determined were expressed in terms of milligrams of the total protein (22).
Assay of Catalase
In the UV range, H2O2 shows a continuous increase in the absorption with decreasing wavelength. The decomposition of H2O2 can be followed directly by the decrease in the absorbance at 240 nm. The difference in absorbance (ΔA) per unit time is a measure of the catalase activity. The units of the CAT activity which were determined were expressed in terms of nmolH2O2/mg protein (23).
Statistical analysis
For each group, the mean± SEM was calculated and the data was analyzed by using one way ANOVA, followed by the Tukey-Kramer multiple comparison test. P values of <0.05 were considered to be statistically significant.

Results

In the present study, the administration of the standard drugs and all the doses of the test drug, 30 min prior to the administration of the haloperidol dose on the fourteenth day, showed significantly (P<0.001) lower cataleptic scores than in the toxic control group in a dose and time dependent manner.
TBARS Activity
The TBARS levels were found to be significantly increased (p<.001) in the brain tissue of the haloperidol (2 mg/kg p.o.) treated animals, as shown in (Table/Fig 4).
GLUTATHIONE Activity
There was a significant increase (p<.05) in the levels of GSH in the Mentha arvensis pretreated mice as compared to the haloperidol 2 mg/kg p.o treated mice.
SOD Activity
In the mice who were pretreated with Mentha arvensis, the levels of SOD were significantly reduced (p<.001) as compared to those in the haloperidol 2 mg/kg p.o. treated mice (Table/Fig 4) shows the effect of the significant and dose dependent recovery on the haloperidol induced elevation of the SOD levels in animals.
CATALASE Activity
There was a significant increase (p<.001) in the levels of catalase in the Metha arvensis pretreated mice as compared to the haloperidol 2 mg/kg p.o. treated mice, as shown in (Table/Fig 4)

Discussion

The treatment with haloperidol often because distressing side effect involving the extra-pyramidal tract these adverse reactions comprise of variety of movement disorders, including drug induced Parkinsonism (25). This occurs in 20-40% of the patient population. The chronic use of haloperidol sometimes leads to irreversiable extra pyramidal disturbances such as tardive dyskinaesia. Similar disorders are reproducible in normal monkeys who are treated for many months with haloperidol and so, these symptoms are not merely an interaction between the psychotic state and the drug effects are largely due to the drug alone. Since haloperidol induced catalepsy had an underlying pathology of increased oxidative stress and as Mentha arvensis was high anti oxidants, in the present study, the effect of Mentha arvensis was evaluated in haloperidol induced cataleptic mice. In the present study, the animals who were treated for fourteen days with haloperidol showed severe cataleptic responses. Further, the animals (haloperidol treated) showed decreased levels of glutathione and catalase and increased levels of lipid peroxidation products and super oxide dismutase as compared to the vehicle toxic control animals. This result was in agreement with that of previous studies which were done on the effects of haloperidol on the extra pyramidal symptoms and the markers of oxidative stress (GSH, SOD, CAT and TBARS), thus suggesting the possible induction of free radical generation by haloperidol treatment. The results of our study were consistent with previous reports of the studies which were done on haloperidol induced oxidative stress (26). But the exact mechanisms by which haloperidol increased free radical production were not clear. The enzymatic degradation by MAOs was associated with the production of hydrogen peroxide, which was readily converted to the hydroxyl radical in the presence of iron. Thus, it could initiate a destructive lipid peroxidation cascade, but an increased dopamine (DA) turnover, leading to hydrogen peroxide production which might not be exclusively involved in the degeneration of oxidative stress. The auto-oxidation of DA which resulted in the production of superoxide radicals might have contributed to the unbalanced production of the free radicals. However, other mechanisms may also be involved. Haloperidol was reported to suppress the activity of certain detoxifying enzymes, thus leaving the cell unprotected, especially if the basal enzyme activity was low or if the free radical scavenging mechanisms were less effective. Haloperidol (HP) is converted to potentially toxic (HHP+) metabolites which may play a role in the extrapyrimidal side effects which are observed in the patients who are treated with haloperidol (27). Another possible mechanism could be the effect of neuroleptics on the mitochondrial respiration. The metabolites of haloperidol inhibit complex-I of the electron transport chain (28). The capability of the anti-psychotic drugs to clinically induce the extra-pyramidal syndrome seems to correlate well with their inhibitory effect on the complex- I inhibition. Whatever could have been be the mechanism of the unbalanced production of the reactive oxygen species (ROS) and the oxidative stress by haloperidol, Mentha arvensis was found to be effective in decreasing the oxidative stress in the haloperidol treated animals. The anti-oxidative properties of Mentha arvensis reduced the duration of the catalepsy, decreased the elevated levels of lipid peroxidation in the haloperidol treated animals and elevated the cellular defense mechanisms such as glutathione, further suggesting the role of free radicals in the pathophysiology of the haloperidol induced extra-pyramidal syndrome. The anti-oxidant activity of pudina could be possibly due to the direct scavenging of the superoxide radicals by the polyphenols or the flavanoids which are known to be present in these drugs. The combination of black tea and Mentha arvensis was found to be more effective than black tea or Mentha arvensis alone. From the present study, it can be concluded that Mentha arvensis may prove to be a beneficial adjuvant in the treatment of drug-induced extrapyramidal side effects and related disorders. The above results have given strong evidence for the further evaluation of the use of Mentha arvensis in combination therapy along with typical antipsychotic agents like haloperidol.

References

1.
Goldstein SR, Matsummoto RR, Thompson TL, Patrick RL, Bowen WD, Walker JM. Motor effect of two sigma ligands which was mediated by nigrostraital dopamine neurons. Synapse 1998; 4:254-58.
2.
Seeman P, Corbett R, Nam D, Van Tol HH. Dopamine and serotonin receptors: Amino acid sequences, and their clinical roles in neuroleptic Parkinsonism. Jpn J Pharmacol 1996; 71: 187-204.
3.
Kulkarni SK, Naidu PS. Tardive dyskinesia: An update. Drugs of Today 2001; 37:97-119.
4.
Cadet JL, Lohr JB, Jested V. Free radical and tardive dyskinesia. Trends Neurosci 1986; 9:107-08.
5.
Eranti VS, Gangadhar BN, Jankiramaiah N. Haloperidol induced extra-pyramidal reaction: lack of the preventive effect of vitamin E. Psychopharmacology 1998; 140:418-20.
6.
Mackay AVP, Iversen LL, Rosser M, Spokes E, Brid E, Arregui A, et al. Increased brain dopamine receptor in schizopherenia. Arch Gen Psychiatry 1982; 39:991-97.
7.
Mahdik SP, Mukherjee S. Free radical pathology and anti-oxidant defense in schizopherenia: a review. Schizophr Res 1996; 19:1-17.
8.
Shivakumar BR, Ravindranath V. Oxidative stress and induced by administration of the Neuroleptics drug haloperidol attenuated by higher doses of haloperidol. Brain Research 1992; 595:256-62.
9.
Shivakumar BR, Ravindranath V .Oxidative stress and thiol modification which was induced by chronic haloperidol administration. J Pharmacol Exp Ther 1993;265:1137-41
10.
Floyd RA, Carney JM. Free radical damage to protein and DNA: A mechanism which is involved and the relevant observation in brain undergoing oxidative stress. Ann Neurol 1992; 32:S22-27.
11.
Dorman HJ, Kos¸ ar M, Kahlos K, HolmY, Hiltunen R. The anti-oxidant properties and the composition of the aqueous extracts from Mentha species, hybrids varieties, and cultivars. J Agric Food Chem 2003; 51(16):4563-99.
12.
Yamada H, Momose T, Okada M, Kuroiwa Y. Anti-cholinergic drugs: response of Parkinsonism not responsive to levodopa. J Neurol Neurosurg Psychiatry 2002; 72(1):111-13.
13.
Coutinho HD, Costa JG, Lima EO, Falcao-Silva VS, Siqueira-Junior JP. The potentiating effect of Mentha arvensis and chlorpromazine on the resistance to aminoglycosides of Methicillin – Resistant Staphylococcus aureus. In Vivo 2009; 23(2):287-89.
14.
Sharma N, Jocob D. The anti-fertility investigation and the toxicological screening of the petroleum ether extract of the leaves of Mentha arvensis L. in male albino mice. Ethnopharmacol. 2001; 75(1):5-12.
15.
Chowdhury BR, Chakraborty R, Raychaudhuri U. Study on the betagalactosidase enzymatic activity of herbal yogurt. Int J Food Sci Nutr 2008; 59(2):116-22.
16.
Jagetia GC. The radioprotective potential of plants and herbs against the effects of ionizing radiation. J Clin Biochem Nutr 2007;40(2):74-81.
17.
Jagetia GC, Baliga MS. Influence of the leaf extract of Mentha arvensis Linn. (Mint) on the survival of mice who were exposed to different doses of gamma radiation. Strahlentherapie and Onkologie 2002; 178:91-98.
18.
Sanjay N Mandhane, Rahul T. Adenosinergic modulation of drug induced catalepsy in mice. Psychopharmacology 1999; 144:398-404.
19.
Lennert H, Hoyer S. The intra-cerebroventicular administration of streptozocin causes long term diminution in the learning and memory abilities and in the cerebral energy metabolism in adult rats. Behav Neurosci 1998; 112:1199-208.
20.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by the thiobarbituric acid reaction. Anal Biochem 1979; 95:359-64.
21.
Sedlak J, Lindsay RH. Estimation of the total protein (bound) and the nonprotein sulfhydryl groups in tissues by using Ellman’s reagent. Anal. Biochem 1968; 25:192-205.
22.
Clairbone A. Assay of Catalase. In: Greenwald RA, ed. Hand book of method of oxygen free radical research; Boca Raton,Fla; CRC press;1985;283-84.
23.
Marklund S, Marklund G. Involvement of the super oxide anion radical in the auto oxidation of pyrogallol and a convenient assay for super oxide dismutase. Eur J Biochem 1974; 47:469-74.
24.
Peterson GL. A review on the folin phenol protein quantification method of Lowry, Rosenbrough, Farr and Randall. Anal Biochem 1979; 100:201-20.
25.
Marsedan CD, Jenner P. The pathophysiology of the extra-pyramidal side effects of neuroleptic drugs. Pshchol Med 1980; 10:55-72.
26.
Sagara Y. Induction of reactive oxygen species in neurons by haloperidol. J Neurochem 1998; 71:1002-12.
27.
Garrod JW, Fang J. The metabolism of haloperidol. Xenobiotica 1993; 23:495-508.
28.
Burkhardt C, Kelly JP, Lim YH, Filley CM, Prker WDJ. Neuroleptic medication inhibits complex–I of the electron transport chain. Ann Neurol 1993; 33:512-17.

DOI and Others

DOI: JCDR/2012/3748:1958

Financial OR OTHER COMPETING INTERESTS:
None.


Date of Submission: Nov 29, 2011
Date of Peer Review: Jan 01, 2012
Date of Acceptance: Jan 09, 2012
Date of Publishing: May 01, 2012

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)
  • www.omnimedicalsearch.com