Day 1 :
Keynote Forum
Hamdy Dawoud
Suez Canal University, Saudi Arabia
Keynote: Molecular surveillance of Plasmodium falciparum chloroquine resistance transporter variant t76 in Jazan area, Kingdom of Saudi Arabia
Biography:
Hamdy Dawoud is a Professor in the Faculty of Medicine, Suez Canal University. He is a Medical and Educational expert in using the Problem Based Learning Curriculum. He is an Active Member
for the Student’s Assessment Committee Designing the Exams and Formulating the PBL. He used to be In-charge of the Designing and Application of the Integrated Curriculum for Jazan Medical School, KSA. He is a Chairman of SAC that reviews the written, practical and clinical exams, is an expert in the analysis of the exams results according to the international standards of reliability, facility and discrimination indices. In Jazan Medical School, he was In-charge of Faculty Development Program that provides the recent advances for the new methods of instructions. Lecturing for the Faculty Staff about the New Innovations for the Medical Curriculum; he got the
experience in the designing of the community based medical curricula, and has attended many seminars all over the worlds.
Abstract:
The development of chloroquine as an antimalarial drug and the
subsequent evolution of drug resistant Plasmodium strains had major impacts on global public health in the 20th century. In P. falciparum, the cause of the most lethal human malaria, chloroquine resistance is linked to multiple mutations in PfCRT, a protein that likely functions as a transporter in the parasite's digestive vacuole membrane. Rapid diagnostic assays for PfCRT mutations are already employed as surveillance tools for drug resistance. Saudi Arabia is still considered by WHO to be in the zone of chloroquine-sensitive countries. However, several reports have been published demonstrating cases with CO resistance. Sporadic cases
have been reported as well as one large scale study demonstrated 12.4% resistance. However, all these reports were based on treatment failure (in vivo) rather than in vitro or molecular bases. Recent evidence suggests a crucial role for a point mutation in the P. falciparum chloroquine resistance transporter (pfcrt) gene on chromosome 7 in conferring CQ resistance In this study we detected mutation in the K76 codon in three cases out of 60 (5%) using ApoI restriction enzyme. Although the percentage of drug resistance is not quite disturbing, but it could represent the possible establishment of chloroquine-resistant P. falciparum in Saudi Arabia, or the
beginning of the spread of resistant strains by labors coming from countries with established resistance to this country. Also, cross-border importation of resistant strains from neighboring countries such as Yemen needs to be considered. In vivo tests need to be conducted in parallel with the molecular markers to estimate more precisely the actual prevalence of resistance. Validation of molecular markers is therefore urgently required and needs strong collaborative partnerships between sub regional and regional
networks.
Keynote Forum
Hamdy Dawoud
Suez Canal University, Saudi Arabia
Keynote: Molecular surveillance of Plasmodium falciparum chloroquine resistance transporter variant t76 in Jazan area, Kingdom of Saudi Arabia
Time : 09:30-10:15
Biography:
Hamdy Dawoud is a Professor in the Faculty of Medicine, Suez Canal University. He is a Medical and Educational expert in using the Problem Based Learning Curriculum. He is an Active Member
for the Student’s Assessment Committee Designing the Exams and Formulating the PBL. He used to be In-charge of the Designing and Application of the Integrated Curriculum for Jazan Medical School, KSA. He is a Chairman of SAC that reviews the written, practical and clinical exams, is an expert in the analysis of the exams results according to the international standards of reliability, facility and discrimination indices. In Jazan Medical School, he was In-charge of Faculty Development Program that provides the recent advances for the new methods of instructions. Lecturing for the Faculty Staff about the New Innovations for the Medical Curriculum; he got the
experience in the designing of the community based medical curricula, and has attended many seminars all over the worlds.
Abstract:
The development of chloroquine as an antimalarial drug and the
subsequent evolution of drug resistant Plasmodium strains had major impacts on global public health in the 20th century. In P. falciparum, the cause of the most lethal human malaria, chloroquine resistance is linked to multiple mutations in PfCRT, a protein that likely functions as a transporter in the parasite's digestive vacuole membrane. Rapid diagnostic assays for PfCRT mutations are already employed as surveillance tools for drug resistance. Saudi Arabia is still considered by WHO to be in the zone of chloroquine-sensitive countries. However, several reports have been published demonstrating cases with CO resistance. Sporadic cases
have been reported as well as one large scale study demonstrated 12.4% resistance. However, all these reports were based on treatment failure (in vivo) rather than in vitro or molecular bases. Recent evidence suggests a crucial role for a point mutation in the P. falciparum chloroquine resistance transporter (pfcrt) gene on chromosome 7 in conferring CQ resistance In this study we detected mutation in the K76 codon in three cases out of 60 (5%) using ApoI restriction enzyme. Although the percentage of drug resistance is not quite disturbing, but it could represent the possible establishment of chloroquine-resistant P. falciparum in Saudi Arabia, or the
beginning of the spread of resistant strains by labors coming from countries with established resistance to this country. Also, cross-border importation of resistant strains from neighboring countries such as Yemen needs to be considered. In vivo tests need to be conducted in parallel with the molecular markers to estimate more precisely the actual prevalence of resistance. Validation of molecular markers is therefore urgently required and needs strong collaborative partnerships between sub regional and regional
networks.
Keynote Forum
Alicia Reyes-Arellano
Instituto Politécnico Nacional, Mexico
Keynote: Design, synthesis and evaluation of 3-substituted quinoxalin-2(1H)-one derivatives as quorum sensing inhibitors compounds in gram-negative bacteria
Biography:
Alicia Reyes-Arellano studied Chemistry at Facultad de Química, UNAM in Mexico, and graduated in 1980. In 1989 she has obtained MSc degree in Organic Chemistry at ENCB, IPN in Mexico. In 1994 she has received from the Institute of Organic Chemistry of the University of Essen, Germany, the PhD in Organic Chemistry. She performed a Postdoc at the Universitat Autónoma of Barcelona, Spain in the Institute of Material Science. Later she became Investigative Group Leader at the Escuela Nacional de Ciencias Biológicas IPN in Mexico City. She worked over the years in
several fields of Organic Chemistry.
Abstract:
The genus Aeromonas is constituted by waterborne gram-negative bacteria that live in aquatic environments, including ground water and chlorinated drinking water. Aeromonas caviae is a specific species considered pathogenic to humans because of causing intra- and extra-intestinal infections, and other severe illnesses, such as septicemia, wounds infection, and respiratory tract disease. The Aeromonas mechanism of pathogenicity is not yet completely understood, but what is known and studied is the significant role of biofilm-formation, undertaken by these types of bacteria. The biofilm structure is a tight association of microorganisms growing on surfaces and embedded in a matrix of extracellular polymeric substance, which exacerbates human infection, by hindering the access of antibiotics to the bacteria. Biofilm constitute an intricate interplay between physical and chemical factors, and have physiological and genetic properties such as gene transfer and gene activation through bacterial communication known as quorum sensing. The quorum sensing communication system is based on small molecules called autoinducers, which trigger biofilm formation. This small molecule signaling construct provides the target for a pharmaceutical chemistry intervention. With the design and synthesis of quorum sensing inhibitors small molecules, the bacteria communication, essential for biofilm-formation, can be blocked. As a result, the pathogenic development is dismantled and additionally the access of antibiotics is promoted. In our group we were able to design and synthesis a pilot series of 3-substituted quinoxalin-2(1H)-one derivatives as anti-quorum sensing compounds. We synthesized these compounds in a two-step synthesis path, initiated by a Grignard reaction to synthesize 2-keto ethyl ester intermediates and finalized in a second condensation step with 2, 3-diamino phenyl. Biofilm-formation was evaluated in transparent flat bottom 24 well plates with a concentration of Aeromonas caviae Sch3 of 2.0 McFarland. At 100 μM compound concentration the best quorum sensing inhibitors molecule Cpd8 reduced the biofilm-formation by 60%. At lower concentrations of 10 and 1 μM reduction of biofilm-formation was still observed. The 3-substituted quinoxalin-2(1H)-one derivatives also was tested in C. violaceum and it was confirmed the quorum sensing activity.
Keynote Forum
Elza Nikoleishvili
The University of Georgia, Georgia
Keynote: Academia (university study programs) involvement in pharmacovigilance in Georgia
Time : 11:20-12:05
Biography:
Elza Nikoleishvili has completed her PhD, from Tbilisi State Medical University. She is the Head of Pharmacy Department, Professor of The University of Georgia. She has over 11 Deposit Certificate of Systematic full continuous educational programs from National Intellectual Property Center of Georgia. She has published more than 20 scientific articles. She is Member of Editorial Board of the Caucasus Journal of Health Sciences and Public Health and expert of Doctoral Programs of Shota Rustaveli National Science Foundation of Georgia.
Abstract:
Nowadays, when we are talking about global education and global
health, Academia must be in the forefront for socio-economic,
cultural and healthcare developing of the country. We have several biggest global challenges among them most important is improving of healthcare. Serious challenges to global health remain ranging from dealing with pandemics to the rise of the cost of care of noncommunicable diseases. For improving healthcare system in developing and developed countries we need professionals with deep theoretical knowledge, practical and clinical skills based on Ethic and Moral Principles and Codes. We have very big positive results of medication of many serious acute and chronic diseases, but also adverse drug reactions (ADRs) cause serious health problems. National Center for Health Statistics USA indicate that ADRs account for approximately 5 % of all acute hospitalization. Among medical errors medication errors are the 5 cause of death of patients. According to bulletin of the WHO 2018 in high-income countries, clinical pharmacy services have been shown to improve quality use of medicines and reduce drug-related problems, hospital readmissions and healthcare expenditures. Meaningful role of clinical pharmacy is to provide rational pharmacotherapy, which includes: effectiveness, safety, suitability
and cost of medication. That is reason why we have seen very deep link between Clinical Pharmacy and Pharmacovigilance. Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. In 2019 Uppsala Monitoring Centre united 136 full members and 29 associate members. In 2018 Georgia has become a member of Uppsala Monitoring Centre. It gives us more possibility to participate and be more active in this direction, to involve our healthcare professionals and patients as well. Pharmacovigilance plays an important role in the rational use of medicines by providing information about adverse drug reactions (ADRs) in the general population. In Georgia Clinical Pharmacy, Parmacovigilance and pharmacotherapy education faces own/specific challenges. As a representative of academia, we understand the importance of pharmacovigilance in the context of Pharmacotherapy. Clinical
Pharmacology, Toxicology and Pharmacotherapy curricula should give a higher priority to the study of the safety of medicines, but the results of the study conducted in Georgia “Barriers of development of Clinical Pharmacy among the healthcare professionals in Georgia” identified lack of: space, enough personnel in pharmacy to handle routine technical tasks, time, need for too much effort, and need for payment for services, clinically qualified pharmacists, poor pharmaceutical literacy among patients, as well as aggressive and inaccurate marketing and advertising, lack of drug information. In 2016 Pharmacy Department created new Master program in Pharmacy and got National accreditation.Our curriculum was first in Georgian academic area in which we included pharmacovigilance and pharmacoepidemiology as independent subjects. As a professionals of medicine and pharmacy spheres we are aware of need for pharmacovigilance in Georgia. It is very important that competency-based educational models are becoming more dominant. In the context of pharmacotherapy competencies in pharmacovigilance are timely recognition, prevention and management of ADRs. From 2019 we begun to use student oriented teaching methods. In order to strengthen competencies we have begun to use task-based learning tools in subjects: clinical Pharmacy, pharmacotherapy and Pharmaceutical care Practice. The School of Health Sciences of the University of Georgia, through study programs and activities, which include seminars, workshops and public lectures, helps to raise awareness about the importance of safe medication for healthcare specialists and patients in Georgia.
- Molecular and Clinical Pharmacology
Chair
Elza Nikoleishvili
The University of Georgia, Georgia
Session Introduction
Melanie Hermann
Evotec SE, Germany
Title: High content histology in drug discovery programs – A tool for target validation
Biography:
Melanie Hermann has completed her PhD at the German Cancer Research Center in Heidelberg, Germany by working on a Transgenic Mouse Model for Skin Cancer. Afterwards she was working as a Postdoc in the Department of Neurosurgery at UCSF, San Francisco, USA, where she did her studies on stroke and traumatic-brain-injury mouse models. Back in Germany, she continued her studies in the Department of Neuropathology at UKE, Hamburg,
Germany by working in the field of Prion disease and the rare Neurodegenerative disease FENIB (familial encephalopathy with neuroserpin inclusion bodies). Afterwards, she has started her carrier in industry and is now working as a Senior Research Scientist on different drug discovery programs at Evotec SE Hamburg by taking the Lead of high content histology approaches for target validation.
Abstract:
Targets arising from either disease relevant animal models, in vitro genetic experiments or the public domain need careful validation and confirmation, ideally prior to initiating a small molecule discovery program. Evotec has developed a number of in and ex vivo models across numerous therapeutic indications to help answer these questions. To maximize the efficiency and robustness of in vivo target modulation, Evotec has implemented an automated histology platform, which aims to identify, localize and validate targets within disease relevant tissues. Together with our in-house expertise in developing unbiased automated image analysis scripts for quantification, the high content histology platform is applied to quantify targets or other relevant factors and proteins within the tissue of choice. In addition, a stereotactic delivery of AAV-shRNA is routinely used to modulate in vivo expression levels and activity of target proteins, to investigate the effects this protein has on cell physiology and disease progression. Furthermore, after successful drug identification, high content histology readouts are used to confirm small molecule effects on disease progression.
Djebbar Atmani
Universite de Bejaia, Algerie
Title: Pistacia lentiscus as a source of bioactive compounds for human health
Biography:
Djebbar Atmani is a Senior Lecturer and Dean of the Faculty of Nature and Life Sciences, University of Bejaia (Algeria). He has obtained his Master of Science degree from California State University, Los Angeles (USA) in 1987 and his PhD from the University of Sétif (Algeria) in 2004. His research interest is Natural Products from Medicinal Plants. He has published over 50 papers in high impact scientific journals and attended several seminars and symposia worldwide and has been serving as Reviewer in several reputed journal.
Abstract:
Medicinal plants are believed to be an important source for the discovery of
potential antioxidant, anticancer, anti-inflammatory and anti-diabetic substances. The present study was designed to investigate the anti-inflammatory, antidiabetic and anticancer potential of Pistacia lentiscus (Anacardiaceae) extracts, as well as identification of active compounds, using appropriate methodology. Oral administration of the crude extracts of leaves and fruits (100 and 200 mg/kg) significantly decreased carrageenan-induced mice paw edema similar to the standard drug Diclofenac (50 mg/kg). Furthermore, Pistacia lentiscus leaf extract was effective in reducing the serum levels of IL-1β compared to acetylsalicylic acid. Blood glucose level was restored to normal values, for both concentrations (50 and 125 mg/kg) tested, in agreement with the in vitro antidiabetic effect. P. lentiscus extracts were also found to be significantly cytotoxic on melanoma B16F10 cell line and showed very good anti-hyperuricemic activity. Phytochemical analysis indicated the presence of copious amounts of flavonoids, tannins and phenolics in the extracts of this plant such as gallic acid, myricetinrhamnoside, quercetin 3-O-rhamnoside, synergic acid and ellagic acid, which could be responsible for the observed activity. Obtained results suggest that Pistacia lentiscus extracts exhibited strong biological effects and may be a candidate for the development of pharmacological agents that may be used in therapy against inflammatory-related disorders.
Wan-Ting Liao
Show Chwan Memorial Hospital, Taiwan
Title: Integrative traditional Chinese medicine therapy reduces risk of type 2 diabetes mellitus in patients with polycystic ovary syndrome
Biography:
Wan-Ting Liao is an Occupational Physician major in Herbalism. She has completed her MD from China Medical University. After finished several research of PCOS and the relationship of PCOS and Diabetes in her Master’s degree in China Medical University, she is now admitted to Institute of Medicine of Chung Shan Medical University for her MD/PhD program.
Abstract:
Polycystic ovary syndrome (PCOS) is a common condition in human beings,
affecting 5-10% of women of reproductive age worldwide. It might lead to a
variety of syndrome such as reproductive, metabolic and mood disorders. The
symptoms of PCOS are complex. The academic circles had made it clear that women with polycystic ovary syndrome have a higher proportion of insulin resistance and are expected to have an increased risk of developing type 2 diabetes in the future. Current treatment of PCOS mainly focuses on symptomatic treatment. This study aimed to understand whether the intervention of traditional Chinese medicine (TCM) in women with PCOS could reduce the risk of type 2 diabetes mellitus. Therefore, we selected the National Health Insurance Database as data source, and randomly selected 1 million enrollees. We identified 684 eligible patients who were newly diagnosed with PCOS in 1997-2010 and underwent blood test of serum testosterone or gynecologic ultrasound. All enrolled cases were 1:1 frequency-matched by age, and diagnosis of PCOS date and index days. Surprisingly, we found that the incidence of type 2 diabetes in TCM groups was significantly lower than in non- TCM group (HR=0.31, 95% CI=0.15-0.64, P=0.0014). Our study suggests that Chinese medicine may play a role in the prevention of subsequent complication of diabetes in patients with PCOS. It is expected that in the future, further clinical research and pharmacological analysis based on these findings.
Abdul Mannan Fateh
University of Malaya, Malaysia
Title: Study of morphogenesis and skeletal abnormalities from an aqueous extract of Verbena officinalis on developing SD embryos
Biography:
Abdul Mannan Fateh is currently studying PhD final year student in Pharmacology Department in the Faculty of Medicine in University Malaya in Malaysia. He has completed his Master’s degree (MSc) in Toxicology Department of Medical Elementology and Toxicology, Hamdard University (New –Delhi) India. He has worked in Medical College from 2008–2013 as a Lecturer in Toxicology in Yemen. He has published three Research Publications in well-reputed ISI journals Q1 and Q2 and high impact factor, participant in two international conferences at Oslo, Norway and Malaysia.
Abstract:
The safety of Verbena officinalis as a traditional herb remedy, in pregnancy and potential effects on foetal morphogenesis, embryo-toxicity and skeletal variations in pups of SD rats, has not yet been tested. This study carried out to
evaluate the potential effects of Verbena officinalis aqueous extract on pregnancy outcome in SD dams. Timed-pregnant of dams from sixth to the 20th day of gestation into five groups (n=10) SD dams received oral single daily of different doses of 3000, 2000, 1000, and 500 mg/kg/day V. officinalis aqueous crude extract of the (vehicle) control during organogenesis. The foetuses were inspected for external morphology and skeletal anomalies. Pups were stained with Alcian blue and Alizarin red. In the present study, the result demonstrated that Verbena officinalis cause embryo-toxicity abnormalities were observed difference with dams rats treated with 3000 and 2000 mg/kg as evidenced by the increased incidence in the post-implantation loss and low measure in the tail length, head cranium, and fetal weight. The total external foetal morphogenesis (stunted growth, micrognathia, subcutaneous hemorrhages and umbilical hernia) abnormalities were differences between all treated groups and control group, however, the higher incidence occurred at 3000 mg (36.2%), whereas some abnormalities of the skeleton such as incomplete ossification of skull and sternebrae, unossified metatarsal bones were observed in foetuses treated with V2000 (19.3%) and V3000 (42.9%) groups. The results of this prenatal study show that consumption of Verbena officinalis boiling tea appears to be unsafe to be used during pregnancy and high does have developmental toxicity on embryos.
Marwa M Safar
The British University, Egypt
Title: Venlafaxine ameliorates complete Freund's adjuvant-induced arthritis in rats via targeting STAT-3/IL-17/RANKL axis
Biography:
Marwa M Safar is an Associate Professor of Pharmacology. She has completed her PhD from Cairo University. Currently, she is the Head of Pharmacology & Biochemistry Department, at the Faculty of Pharmacy, The British University in Egypt. She has published more than 30 articles in reputed journals and supervised more than 15 Masters and PhD thesis.
Abstract:
Rheumatoid arthritis is usually accompanied by various comorbidities especially on the psychological side such as depression. This study aimed at revealing the potential curative effects of venlafaxine (VFX), a serotonin/norepinephrine reuptake inhibitor (SNRI), on experimentally-induced arthritis in rats. Arthritis was induced by injecting complete Freund's adjuvant (CFA, 0.1 ml, s.c.). One day thereafter, VFX (50 mg/kg, p.o.) was given for 21 days. Methotrexate was used as a standard disease modifying antirheumatic drug. CFA injection caused prominent arthritis evident by the increase in the hind paw and ankle diameter accompanied by elevating tumor necrosis factor-alpha, interleukin-6, interleukin-17 and matrix metalloproteinase-3 levels, effects that were diminished by VFX. Moreover, VFX down regulated gene expressions of receptor activator of nuclear factor kappa-B (NF-кB) ligand and signal transducer and activator of transcription-3 beside hampering immunohistochemical expression of vascular endothelial growth factor and NF-кB. This SNRI also improved the oxidant status of the hind limb as compared to the arthritic group. Nonetheless, MTX was better in amendment of arthritis authenticated by its effect on some inflammatory and oxidative stress biomarkers. This study provides a novel therapeutic use of VFX as a considerable anti-arthritic drug and offers an incentive
to expand its use in RA.
Noha F Abdelkader
Cairo University, Egypt
Title: Mechanisms underlying the gastroprotective effect of irbesartan aganist indomethacin-induced ulcer in rats
Time : 15:30-16:00
Biography:
Noha F Abdelkader has completed her PhD from the Faculty of Pharmacy, Cairo University, Egypt. She is an Associate Professor in Pharmacology and Toxicology Department, in the Faculty of Pharmacy, Cairo University. She has published 15 papers in reputed journals in addition to a number of conference proceedings. Her main research is focused on Neurodegenerative Disorders, Drug-Induced Toxicities, and Drug Repurposing. She has coordinated the Erasmus funded project IT-Based International Diploma and Professional Certificate in Clinical Toxicology. She is currently a Member of Egyptian Society of Pharmacology and Experimental Therapeutics, Pharmacology for AFRICA’ initiative and International Association of Therapeutic Drug Monitoring and Clinical Toxicology.
Abstract:
Recently, angiotensin II type 1 receptor blockers (ARBs) has emerged as a potential gastroprotective candidates. Thus, the aim of the current study was to investigate the gastroprotective potential of irbesartan in a rat model of gastric injury. Adult male Wistar rats were randomly allocated into five groups. Group I rats served as a control group. Group II rats were treated with irbesartan. Rats of groups III-V were treated with indomethacin. Wherase, groups IV and V were pretreated with ranitidine, as a reference anti-ulcer drug, and irbesartan; respectively. Irbesartan (50 mg/Kg, p.o) was administered once daily for two weeks; thereafter, gastric injury was induced by indomethacin (60 mg/Kg, p.o). Treatment with irbesartan mitigated indomethacin-induced elevation in gastric ulcer index and acidity, gastric mucosal apoptotic and inflammatory aberrations, as demonstrated by hampering caspase-3, prostaglandin E2 and tumor necrosis factor-alpha levels and cyclooxygenase-2 mRNA expression. Furthermore, irbesartan increased mucosal dimethylarginine dimethylaminohydrolase-1 (DDAH-1) gene expression and decreased elevated levels of matrix metalloproteinase-9, asymmetric dimethylarginine (ADMA), epidermal growth factor receptor (EGFR) mRNA and phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2). Morover, irbesartan ameliorated gastric histopathological alterations. Overall efficacy of irbesartan was comparable to ranitidine, the widely used H2 receptor blocker. In conclusion, irbesartan exhibited a significant gastroprotective effect against indomethacin-induced mucosal damage via acid-inhibitory, antiinflammatory, anti-apoptotic and extracellular matrix remodeling mechanisms that are probably mediated, at least partly, by down-regulating DDAH/ ADMA and EGFR/ERK1/2 signaling.
Naile Merve Guven
Ankara University, Turkey
Title: Role of oxidative stress and polycystic ovary syndrome
Time : 16:00-16:30
Biography:
Naile Merve Güven has been a Research Assistant at Ankara University, Faculty of Pharmacy, in the Department of Pharmaceutical Toxicology since 2018. She earned her Master's degree in the same Department in July 2019. She is currently a PhD student in the same Department. Her research interests cover CYP450 Enzymes, Diabetes Mellitus and Polycystic Ovary Syndrome. She has experience with microsome isolation from rat liver, protein determination by BCA, western blot, isolation of mononuclear cells from whole blood.
Abstract:
Polycystic ovary syndrome (PCOS), characterized by oligo-ovulation or anovulation, elevated androgens, and appearance of polycystic ovaries, is an endocrine disorder that affects women of childbearing age. Prevalence of PCOS varies between 6-15% according to different diagnostic criteria. Insulin resistance and related compensatory hyperinsulinemia play a critical role in the pathophysiology of PCOS. According to the results of various studies, up to 70% of women with PCOS have insulin resistance. Studies in adipocyte and skeletal muscle cells have reported that insulin resistance in PCOS is mediated by receptor-mediated signal transduction or post-receptor defect. Besides, defects in insulin signaling as a result of impaired insulin receptor tyrosine kinase activity in skin fibroblasts have been described. Although the underlying mechanism of oxidative stress in PCOS is not fully understood, it has been shown that insulin resistance promotes oxidative stress. Increased reactive oxygen species in case of oxidative stress are produced by mitochondria. The ovary, testis, and uterus are particularly affected by reactive
oxygen species because they are regions that require ATP and contain high levels of mitochondria. Oxidative stress has a harmful effect, which may influence the fertility of women negatively, on ovulation, fertilization, embryo development, and implantation. Oxidative stress plays a significant role in the process of ovulation by inducing apoptosis of luteal cells. Oxidative stress in the follicular fluid may cause inadequate oocyte and embryo development.