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

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Dr Mohan Z Mani

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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."



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Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
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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.
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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

Original article / research
Year : 2022 | Month : October | Volume : 16 | Issue : 10 | Page : FC10 - FC14 Full Version

Evaluation of Antioxidant Effects of Antiepileptic Drugs in Adult Epileptic Patients: An Open Label, Non Randomised Interventional Study


Published: October 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/57376.17106
B Swathi, D Aruna

1. Assistant Professor, Department of Pharmacology, Osmania Medical College, Hyderabad, Telangana, India. 2. Additional Professor, Department of Clinical Pharmacology and Therapeutics, Nizams Institute of Medical Sciences, Hyderabad, Telangana, India.

Correspondence Address :
Dr. B Swathi,
Osmania Medical College Koti, Hyderabad-500095, Telangana, India.
E-mail: swathiburlambbs@gmail.com

Abstract

Introduction: Oxidative stress is one of the factors implicated in the pathogenesis of epilepsy. Various antiepileptic drugs can control seizures by several mechanisms that may involve reduction of oxidative stress. Only a few studies have evaluated the antioxidant effects of Antiepileptic Drugs (AEDs).

Aim: To evaluate the antioxidant activity of the AEDs (Phenytoin, Levetiracetam, Oxcarbazepine) in adult epileptic patients.

Materials and Methods: The present open label, non randomised interventional study was conducted at the tertiary care hospital, Hyderabad, Telangana, India, from September 2016 to November 2017. Total of 45 subjects were divided into three groups, Phenytoin group, Levetiracetam group and Oxcarbazepine group with 15 patients in each group. Blood samples were collected prior to initiation of treatment and after three months of treatment for measurement of antioxidative parameters such as Malondialdehyde (MDA), Nitric Oxide (NO) and reduced Glutathione (GSH) levels. Paired t-test was used for within group analysis.

Results: Amongst the total subjects of 45,(15 in each group), 14 subjects in phenytoin group, 12 in Levetiracetam group and 13 in oxcarbazepine group were finally analysed. The mean age was 28.92±9.62 years, mean weight was 55.87±10.73 kg and mean Body Mass Index (BMI) was 21.99±3.82 kg/m2. No statistically significant difference was seen in all oxidative parameters in phenytoin treated group. In levetiracetam group, significant decrease in MDA levels (p-value- 0.0338) and increase in GSH levels (p-value <0.0001) was observed after three months of treatment. In oxcarbazepine group, statistically significant decrease was found in MDA (p-value-0.0055) and NO levels (p-value-0.016) and increase in GSH levels (p-value- 0.0004) was observed.

Conclusion: It was concluded that phenytoin has no role in reducing oxidative stress in epileptic patients, whereas levetiracetam decreases lipid peroxidation and oxcarbazepine has beneficial role in reducing oxidative stress in adult epileptic patients.

Keywords

Levetiracetam, Malondialdehyde, Nitric oxide, Oxcarbazepine, Phenytoin, Reduced glutathione

Epilepsy is one of the common chronic neurological disorders, afflicting nearly 50 million people worldwide and 80% of this population are living in low-and middle-income countries (1). Approximately 10-12 million persons with epilepsy are residing in India, with more prevalence in rural areas compared to urban population (1). According to International League Against Epilepsy (ILAE), epilepsy is defined as, “Atleast two unprovoked (or reflex) seizures occurring >24 hours apart; one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (atleast 60%) after two unprovoked seizures, occurring over the next 10 years; and diagnosis of an epilepsy syndrome” (2). Several pathophysiological processes or mechanisms that lead to the occurrence of first spontaneous seizure and subsequent epilepsy events have been proposed. The mechanisms that contribute to epileptogenesis are neurotransmission signalling pathway abnormality, imbalance in ion charges due to channelopathies, aberrant hippocampal neurogenesis and several others (3). Current AEDs aims to modulate one of these pathological processes (3). Thorough understanding of the pathogenesis forms the basis for development of new therapies that aim to prevent or halt the progression of epileptogenesis.

Various studies suggest the role of oxidative stress in the pathophysiology of epilepsy (4),(5). Oxidative stress is an imbalance between formation and removal of Reactive Oxygen Species (ROS) in favour of the former. Brain is particularly vulnerable to oxidative stress because it has large quantity of mitochondria, consumes highest amount of oxygen and it has limited antioxidant system. Brain is rich in polyunsaturated fatty acids which are targets for ROS, and also rich in iron which catalyses ROS formation. Catalase, which is an enzymatic antioxidant defence system, is quite low in brain compared to other organs (6).

Oxidative stress and formation of ROS leads to abnormal structural alteration in biological macromolecules namely cellular proteins, membrane lipids, carbohydrates and nucleic acids (7). Alteration in cellular structure and functions of biomolecules, consequently lead to cellular death. Several animal models of epilepsy have demonstrated increased ROS production in epilepsy leading to mitochondrial dysfunction and apoptosis in neurons mainly in hippocampal region of brain (8),(9). Many studies have confirmed increased oxidative stress in untreated patients with epilepsy in terms of increased lipid peroxidation reflected by elevated MDA levels and increased NO levels and reduced GSH activity. Furthermore, it was reported that exogenous administration of antioxidants significantly reduced seizures (10),(11).

Regardless of abundance of drugs for epilepsy, 20-30% patients still continue to have seizures (10). Antioxidant activity of phenytoin has been evaluated in several animal models but the reports were inconclusive (12),(13). Oliveira AA et al., demonstrated that levetiracetam pre-treatment in pilocarpine induced seizures significantly decreased lipid peroxidation and nitrite-nitrate levels and prevented the loss of GSH in hippocampal region of mice brain and it was postulated that levetiracetam ability to block the calcium influx into cells might contributing to its activity against oxidative stress (14). In children with idiopathic epilepsy oxcarbazepine treatment resulted in decrease in MDA levels after three and six months of treatment and reduced NO levels after three months of treatment (15).

Limited number of studies have evaluated antioxidant effects of AEDs (14),(15). But most of these studies were done in animal models and children with epilepsy using NO, lipid peroxidation and xanthine oxidase system parameters for evaluating antioxidant status (14),(15). Some of these studies (13) concluded increase in oxidative stress, while others (15) decrease in oxidative stress. Hence the present study was aimed at evaluating the antioxidant activity of the AEDs (phenytoin, levetiracetam, oxcarbazepine) in adult epileptic patients.

Material and Methods

The present open label, non randomised interventional study was conducted at the tertiary care hospital, Hyderabad, Telangana, India, from September 2016 to November 2017. The study was registered with clinical trial registry-India (CTRI/2017/12/010840). Approval of Institutional Ethics Committee (IEC) (EC/NIMS/1792/2016) was taken prior to initiation of the study. Written informed consent was obtained from all the eligible patients prior to the study.

Inclusion criteria: Newly diagnosed drug naive epileptic patients aged between 18-60 years of either gender, who were initiated on monotherapy with phenytoin or levetiracetam or oxcarbazepine, and willing to give informed consent were included in the study.

Exclusion criteria: Patients with history of psychiatric or progressive neurological disorders, other co-morbid conditions like ischaemic heart disease, kidney disease, liver disease, thyroid disorders and other endocrinopathies, history of diseases that could influence the level of oxidative stress, such as diabetes mellitus, arterial hypertension, malignancies, recent surgery and trauma, and patients on drugs that influence the level of oxidative stress such as vitamins, herbal medicines for the last three months, pregnant and lactating women were excluded from the study.

Classification of seizures was based on International League Against Epilepsy (ILAE) 2017 classification of seizure types (16), it includes focal onset with impaired awareness, focal onset with awareness, generalised onset, combined generalised and focal epilepsy, and unknown category. Temporal lobe epilepsy is the most common type of focal onset seizures.

Sample size estimation: A total sample size of 45 was required based on the study by Arhan E et al., (15), with predicted decrease in MDA levels after three months of treatment for oxcarbazepine compared to baseline of 0.7 nmol/mL with Standard Deviation (SD) of 0.80 nmol/ml with 85% power, type 1α error of 5% and dropout rate of 20% (Table/Fig 1).

Procedure

Patient demographic details, present history, drug history were noted in case record form. Ten mL of venous blood was collected from each subject prior to initiation of treatment for baseline antioxidant status. All the subjects were divided into three groups:

Phenytoin group: 100 mg tablets or capsules were prescribed, orally, one tablet or capsule in the morning and two tablets or capsules in the evening for three months.

Levetiracetam group: 500 mg tablets, orally, twice daily for three months.

Oxcarbazepine group: 300 mg tablets, orally, twice daily for three months.

Patients were started on AEDs treatment according to physician discretion. After three months of treatment, oxidative parameters and adverse drug reactions were assessed and noted in case record form.

Ten ml of venous blood was collected for antioxidant assessment after three months of treatment. Blood samples were obtained in the interictal period. Oxidative stress was assessed by estimation of MDA, NO and GSH levels using ultraviolet visible spectrophotometer (UV-1601, Schimadzu) (Ellman GL. 1959). MDA, the secondary product of lipid peroxidation, was estimated in the serum samples by thiobarbituric acid reactive acid substance test (17). NO level (μM/L) was estimated by a test that involves reduction of nitrate by vanadium (III) and detection with Griess reagents (18). GSH was estimated by 5, 5-Dithiobis 2-Nitrobenzoic acid (DTNB) method (19).

Statistical Analysis

Data were statistically analysed using GraphPad Prism 7. Data was expressed as mean±standard deviation. Paired t-test was used for within group analysis. One-way Analysis of Variance (ANOVA) followed by post-hoc Tukey’s test was performed for between group comparisons. The p-value <0.05 was considered to be statistically significant.

Results

A total of 58 subjects were screened, 45 subjects were enrolled and remaining 13 subjects were excluded based on the exclusion criteria. Out of 45 subjects, four subjects were lost to follow-up and two withdrew from the study. Total 39 subjects were included in final analysis. The mean age was 28.92±9.62 years. The mean weight was 55.87±10.73 kg. The mean BMI was 21.99±3.82 kg/m2. Among the 39 subjects, 14 were in Phenytoin group, 12 were in Levetiracetam group and 13 were in Oxcarbazepine group. Seizure frequency was assessed before treatment in all the groups. Among the total subjects <3 seizures were observed in 25 subjects, 3-5 seizures in 10 subjects and >5 seizures were observed in four subjects (Table/Fig 2).

The types of seizures observed in total number of subjects were generalised tonic clonic seizures in 29 (74.36%) subjects, focal onset with impaired awareness in 6 (15.39%) subjects, focal onset with awareness in 1 (2.56%) subject and temporal lobe epilepsy in 3 (7.69%) subjects.

All oxidative parameters before treatment in all the three groups were similar and there was no statistically significant difference observed. The oxidative parameters in three groups before treatment and after three months of treatment are shown in (Table/Fig 3),(Table/Fig 4). No statistically significant difference was observed for all the oxidative parameters after three months among all the three groups.

In phenytoin group, there was no statistically significant difference seen after three months of treatment when compared to before treatment values in all oxidative stress parameters. Oxidative parameters before treatment and after three months of treatment in phenytoin group are shown in (Table/Fig 5).

In levetiracetam group, statistically significant decrease (p=0.0338) in MDA levels and significant increase (p<0.0001) in GSH levels was observed after three months of treatment compared to pretreatment levels. There was no statistically significant difference seen in NO levels after three months of treatment when compared to before treatment (Table/Fig 6).

In oxcarbazepine group, there was statistically significant decrease found in MDA (p<0.01) and NO (p=0.016) levels and significant increase (p<0.001) in GSH levels after three months of treatment compared to pretreatment. Oxidative parameters before treatment and after three months of treatment in oxcarbazepine group are shown in (Table/Fig 7).

Among the three groups, number of subjects with seizure free during three months of treatment was 7 (50%) in phenytoin group, 7 (58.33%) in levetiracetam group and 9 (69.23%) in oxcarbazepine group. Out of 13 subjects in oxcarbazepine group, weight gain was observed in 8 (61.54%) subjects. In levetiracetam group, withdrawal seizures were observed in 2 (16.67%) subjects, and ataxia in one (7.14%) subject in phenytoin group.

Discussion

Oxidative stress has been implicated as one of the several pathophysiological mechanisms causing epilepsy (4),(5). Brain is particularly susceptible to lipid peroxidation because it is rich in polyunsaturated fatty acids and mitochondria. ROS have short life span and it is difficult to measure them in-vivo (20). So lipid, protein and DNA peroxidation products are used as indicators of oxidative stress in experimental and clinical studies (4),(5). In the present study, NO level was towards upper limit, whereas GSH level was towards lower limit of normal level at pretreatment in all the three groups. There was no significant difference in MDA, NO and GSH levels in three groups before treatment. Many authors studied (13),(21),(22) the effect of phenytoin on oxidative parameters in experimental animals and in epileptic patients. Present study showed no significant difference in MDA, NO and GSH levels after three months of treatment compared to pretreatment levels in adult epileptic patients treated with phenytoin, but MDA, NO and GSH levels were increased compared to pre-treatment levels.

Present study results were in accordance with a study done by Menon B et al., they evaluated the oxidative parameters in 100 patients with epilepsy and 100 healthy controls. Among the epileptic patients, 66% were on monotherapy, out of which 20% were on phenytoin (21). In this study, there was no significant difference in MDA and NO levels in patients with epilepsy who were on treatment versus who were not on treatment. Present study findings varied from studies done in epileptic patients. A study done by Liu CS et al., in which 20 female epileptics treated with phenytoin monotherapy, there was significant increase in MDA and significant decrease in GSH levels when compared to 12 female epileptics without anticonvulsant therapy and healthy controls (13). In another study done by the Liu CS et al., MDA concentrations were elevated and GSH concentrations decreased in 30 epileptic patients treated with phenytoin monotherapy compared to 35 healthy controls (22).

Ono H et al., enrolled 45 epileptic patients and 53 healthy controls without seizures into the study (23). In this study, they reported that plasma GSH concentrations were significantly lower in epileptic patients treated with carbamazepine or phenytoin monotherapy when compared to healthy controls. Mahle C and Dasgupta A, showed significantly increased concentrations of lipid hydroperoxide and decreased antioxidant capacity in serum samples of phenytoin treated patients when compared to sera of control samples (24). Very few studies (25),(26),(27) evaluated the effect of levetiracetam on oxidative stress in epileptic patients. Present study showed significant decrease in MDA levels and significant increase in GSH levels, but there was no significant difference in NO levels after three months of treatment compared to pretreatment levels. The present study results were in concordance with the two studies conducted by Oliveira AA et al., (14),(25) in mice. As previously stated, Oliveira AA et al., (14) evaluated the effect of levetiracetam on lipid peroxidation level, nitrite-nitrate formation and antioxidant enzymatic activity in mice brain after pilocarpine induced seizures. They found that administration of pilocarpine alone produced significant increase in lipid peroxidation level, nitrite and nitrate formation, catalase activity and decrease in GSH levels. But administration of levetiracetam 60 minutes before pilocarpine counteracted alterations in these levels, preserving the levels in normal range. In another study done by Oliveira ADA et al., (25) it was demonstrated that the effect of levetiracetam on mice brain homogenates after in-vitro induced oxidative stress. The heating-induced oxidative stress showed an increase in lipid peroxidation, nitrite-nitrate content, and catalase activity in mice brain homogenates. Previous incubation with levetiracetam reduced the lipid peroxidation, nitrite-nitrate contents and catalase activity, and increased the GSH levels.

In contrast to these findings Sarangi SC et al., (26) reported a marked increase in MDA levels and decrease in GSH levels in levetiracetam group compared to control group in male wistar rats. The results of the study done by Varoglu AO et al., in epileptic patients were in contrast to present study findings. They studied the effect of valproate, carbamazepine and levetiracetam on antioxidant and oxidant systems in epileptic patients. They observed higher serum 8-hydroxyguanine (8-OHG) level in the patients taking antiepileptic drugs for the first two months than in the controls (27). In another study done in epileptic patients by Ozden H et al., they determined the urinary 15f-2t-isoprostane levels, which is a marker of oxidative stress. After three months of treatment with levetiracetam, urinary 15f-2t-isoprostane levels were elevated compared to pre-treatment levels indicating increase in oxidative stress (28).

The present study showed significantly low levels of MDA and high levels of GSH, but no significant change in NO after three months of treatment compared to initial values, suggesting beneficial role in lipid peroxidation and antioxidant enzyme system. In present study, significant decrease in MDA and NO levels and significant increase in GSH levels after three months of treatment compared to pre-treatment levels were observed. Present study results were consistent with a study done by Arhan E et al., (15). In their study among 49 epileptic children 21, were treated with oxcarbazepine. They observed significant decrease in MDA levels after third and six months compared to pre-treatment values. They also found significant decrease in NO levels after three months however the change was insignificant after six months compared to pretreatment values.

In contrast to present study, oxcarbazepine effect on MDA level was not significant in the study done by Bolayir E et al., they studied the effect of oxcarbazepine on MDA, catalase, glutathione peroxidase and on superoxide dismutase in epileptic patients. There was no significant difference in MDA and catalase levels after one year of treatment compared to pre-treatment values. But a significant difference in GSH peroxidase and superoxide dismutase activities after one year of treatment compared to pre-treatment values (29). The above study results were in contrast to the present study, the reason could be owing to the shorter duration of present study. Further randomised double blind investigations with long-term use of AEDs are required.

Limitation(s)

Study limitations were that there was no healthy control group, small sample size and study duration was shorter, thus to confirm the results, more advanced prospective long-term clinical studies are warranted.

Conclusion

Phenytoin has no role in reducing oxidative stress in epileptic patients, whereas levetiracetam decreases lipid peroxidation. Oxcarbazepine has beneficial role in reducing oxidative stress in adult epileptic patients, because there was reduction in MDA, NO and increase in GSH levels compared to initial values after three months. But thorough analysis will be needed to deduce whether oxcarbazepine has truly favourable action in oxidative stress and whether it is contributing to its antiseizure activity in these patients.

Author’s contribution: Dr. D. Aruna has finalised the draft and guarantor, Dr. B. Swathi has prepared the conceptual framework, designing of draft, and data analysis.

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DOI and Others

DOI: 10.7860/JCDR/2022/57376.17106

Date of Submission: Apr 30, 2022
Date of Peer Review: Jun 14, 2022
Date of Acceptance: Aug 31, 2022
Date of Publishing: Oct 01, 2022

AUTHOR DECLARATION:
• 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? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

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