Linking Benzene, in Utero Carcinogenicity and Fetal Hematopoietic Stem Cell Niches: A Mechanistic Review.

Previous research reported that prolonged benzene exposure during in utero fetal development causes greater fetal abnormalities than in adult-stage exposure. This phenomenon increases the risk for disease development at the fetal stage, particularly carcinogenesis, which is mainly associated with hematological malignancies. Benzene has been reported to potentially act via multiple modes of action that target the hematopoietic stem cell (HSCs) niche, a complex microenvironment in which HSCs and multilineage hematopoietic stem and progenitor cells (HSPCs) reside. Oxidative stress, chromosomal aberration and epigenetic modification are among the known mechanisms mediating benzene-induced genetic and epigenetic modification in fetal stem cells leading to in utero carcinogenesis. Hence, it is crucial to monitor exposure to carcinogenic benzene via environmental, occupational or lifestyle factors among pregnant women. Benzene is a well-known cause of adult leukemia. However, proof of benzene involvement with childhood leukemia remains scarce despite previously reported research linking incidences of hematological disorders and maternal benzene exposure. Furthermore, accumulating evidence has shown that maternal benzene exposure is able to alter the developmental and functional properties of HSPCs, leading to hematological disorders in fetus and children. Since HSPCs are parental blood cells that regulate hematopoiesis during the fetal and adult stages, benzene exposure that targets HSPCs may induce damage to the population and trigger the development of hematological diseases. Therefore, the mechanism of in utero carcinogenicity by benzene in targeting fetal HSPCs is the primary focus of this review.

The Role of Promyelocytic Leukemia Zinc Finger (PLZF) and Glial-Derived Neurotrophic Factor Family Receptor Alpha 1 (GFRα1) in the Cryopreservation of Spermatogonia Stem Cells.

The cryopreservation of spermatogonia stem cells (SSCs) has been widely used as an alternative treatment for infertility. However, cryopreservation itself induces cryoinjury due to oxidative and osmotic stress, leading to reduction in the survival rate and functionality of SSCs. Glial-derived neurotrophic factor family receptor alpha 1 (GFRα1) and promyelocytic leukemia zinc finger (PLZF) are expressed during the self-renewal and differentiation of SSCs, making them key tools for identifying the functionality of SSCs. To the best of our knowledge, the involvement of GFRα1 and PLZF in determining the functionality of SSCs after cryopreservation with therapeutic intervention is limited. Therefore, the purpose of this review is to determine the role of GFRα1 and PLZF as biomarkers for evaluating the functionality of SSCs in cryopreservation with therapeutic intervention. Therapeutic intervention, such as the use of antioxidants, and enhancement in cryopreservation protocols, such as cell encapsulation, cryoprotectant agents (CPA), and equilibrium of time and temperature increase the expression of GFRα1 and PLZF, resulting in maintaining the functionality of SSCs. In conclusion, GFRα1 and PLZF have the potential as biomarkers in cryopreservation with therapeutic intervention of SSCs to ensure the functionality of the stem cells.

The Role of PKC-MAPK Signalling Pathways in the Development of Hyperglycemia-Induced Cardiovascular Complications.

Cardiovascular disease is the most common cause of death among diabetic patients worldwide. Hence, cardiovascular wellbeing in diabetic patients requires utmost importance in disease management. Recent studies have demonstrated that protein kinase C activation plays a vital role in the development of cardiovascular complications via its activation of mitogen-activated protein kinase (MAPK) cascades, also known as PKC-MAPK pathways. In fact, persistent hyperglycaemia in diabetic conditions contribute to preserved PKC activation mediated by excessive production of diacylglycerol (DAG) and oxidative stress. PKC-MAPK pathways are involved in several cellular responses, including enhancing oxidative stress and activating signalling pathways that lead to uncontrolled cardiac and vascular remodelling and their subsequent dysfunction. In this review, we discuss the recent discovery on the role of PKC-MAPK pathways, the mechanisms involved in the development and progression of diabetic cardiovascular complications, and their potential as therapeutic targets for cardiovascular management in diabetic patients.

The Potential Role of Flavonoids in Ameliorating Diabetic Cardiomyopathy via Alleviation of Cardiac Oxidative Stress, Inflammation and Apoptosis.

Diabetic cardiomyopathy is one of the major mortality risk factors among diabetic patients worldwide. It has been established that most of the cardiac structural and functional alterations in the diabetic cardiomyopathy condition resulted from the hyperglycemia-induced persistent oxidative stress in the heart, resulting in the maladaptive responses of inflammation and apoptosis. Flavonoids, the most abundant phytochemical in plants, have been reported to exhibit diverse therapeutic potential in medicine and other biological activities. Flavonoids have been widely studied for their effects in protecting the heart against diabetes-induced cardiomyopathy. The potential of flavonoids in alleviating diabetic cardiomyopathy is mainly related with their remedial actions as anti-hyperglycemic, antioxidant, anti-inflammatory, and anti-apoptotic agents. In this review, we summarize the latest findings of flavonoid treatments on diabetic cardiomyopathy as well as elucidating the mechanisms involved.

Therapeutic Approach of Flavonoid in Ameliorating Diabetic Cardiomyopathy by Targeting Mitochondrial-Induced Oxidative Stress.

Diabetes cardiomyopathy is one of the key factors of mortality among diabetic patients around the globe. One of the prior contributors to the progression of diabetic cardiomyopathy is cardiac mitochondrial dysfunction. The cardiac mitochondrial dysfunction can induce oxidative stress in cardiomyocytes and was found to be the cause of majority of the heart morphological and dynamical changes in diabetic cardiomyopathy. To slow down the occurrence of diabetic cardiomyopathy, it is crucial to discover therapeutic agents that target mitochondrial-induced oxidative stress. Flavonoid is a plentiful phytochemical in plants that shows a wide range of biological actions against human diseases. Flavonoids have been extensively documented for their ability to protect the heart from diabetic cardiomyopathy. Flavonoids' ability to alleviate diabetic cardiomyopathy is primarily attributed to their antioxidant properties. In this review, we present the mechanisms involved in flavonoid therapies in ameliorating mitochondrial-induced oxidative stress in diabetic cardiomyopathy.

Low-dose Nicotine Exposure Induced the Oxidative Damage of Reproductive Organs and Altered the Sperm Characteristics of Adolescent Male Rats.

BACKGROUND: Nicotine is a major toxic and hazardous component of cigarette smoke, and it has been widely used in nicotine replacement therapy (NRT). This study was aimed to investigate the effects of chronic low-dose nicotine on sperm characteristics and reproductive organ integrity in adolescent male Sprague-Dawley rats. METHODS: Twelve rats were equally divided into two groups. Group I received normal saline, and group II received 0.6 mg/kg body weight nicotine intraperitoneally for 28 consecutive days. At the end of the experimental period, sperm was collected for sperm characteristic evaluation, and the testes and prostate were isolated for biochemical and morphological analysis. The effects of nicotine on the body and reproductive organ weights of the animals were evaluated. RESULTS: Chronic nicotine treatment significantly (P < 0.05) altered the sperm count, motility, viability, and morphology, and remarkably increased the malondialdehyde (P < 0.001) and advanced oxidation protein product (P < 0.05) levels in the testes and prostate of nicotine-treated group compared to control group. Moreover, nicotine caused a significant decrease (P < 0.05) in the superoxide dismutase activity of the testes. No significant differences were observed in the reduced glutathione level in both of the testes and prostate of nicotine group compared with control group. Nicotine also induced histopathological alteration in the testes. CONCLUSION: A low-dose nicotine exposure at 0.6 mg/kg caused detrimental effects on sperm characteristics and induced oxidative stress in the testes and prostate.

Effects of palm oil tocotrienol-rich fraction on biochemical and morphological alterations of liver in fenitrothion-treated rats.

Indiscriminate application of organophosphate (OP) pesticides has led to environmental pollution and severe health problems. The aim of the present study was to evaluate the effect of palm oil tocotrienol-rich fraction (TRF) on biochemical and morphological changes of the liver in rats treated with fenitrothion (FNT), a type of OP pesticide. A total of 28 male Sprague-Dawley rats were divided into four groups; control group, TRF-supplemented group, FNT-treated group and TRF+FNT group. TRF (200 mg/kg) was supplemented 30 minutes prior to FNT (20 mg/kg) administration, both orally for 28 consecutive days. Following 28 days of treatment, plasma biochemical changes and liver morphology were evaluated. The body and absolute liver weights were significantly elevated in TRF+FNT group compared to FNT group. TRF administration significantly decreased the total protein level and restored the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in TRF + FNT group. In contrast, total bilirubin level, γ-glutamyltranferase (GGT) and cholinesterase activity in TRF + FNT group did not significantly differ from FNT group. Administration of TRF also prevented FNT-induced morphological changes of liver as observed by electron microscope. In conclusion, TRF supplementation showed potential protective effect towards biochemical and ultrastructural changes in liver induced by FNT.

Antioxidant Activity of Tocotrienol Rich Fraction Prevents Fenitrothion-induced Renal Damage in Rats.

Fenitrothion (FNT) is an organophosphate compound widely used as pesticide in Malaysia. The present study aims to investigate effects of palm oil tocotrienol rich fraction (TRF) on the renal damage of FNT-treated rats. A total of 40 male Sprague Dawley rats were divided into 4 groups randomly, the control, TRF, FNT and FNT+TRF groups. FNT (20 mg/kg b.w.) and TRF (200 mg/kg b.w.) were given orally for 28 days continuously. Rats from the FNT+TRF group were supplemented with TRF 30 minutes prior to administration of FNT. Rats were sacrificed after 28 days, and the kidneys were removed for determination of oxidative stress and histological analysis. Plasma was collected for determination of blood creatinine and urea level. Statistical analysis showed that palm oil TRF has a protective effect against renal oxidative damage induced by FNT. In the FNT+TRF group, malondialdehyde and protein carbonyl levels were significantly lower, while the glutathione level as well as superoxide dismutase and catalase activities were significantly higher compared with the FNT-treated group (p<0.05). As for renal function, there was a markedly lower urea level (p<0.05) in the FNT+TRF group compared with the FNT-treated group, but there was no significant difference in creatinine level. Besides, total protein also showed no significant difference for all groups of rats (p>0.05). Histological evaluation also revealed that the FNT+TRF group had less glomerulus and renal tubule damage than the FNT-treated group. In conclusion, palm oil TRF was able to reduce oxidative stress and renal damage in FNT-treated rats.

The Role of ERα and ERß in Castration-Resistant Prostate Cancer and Current Therapeutic Approaches.

Castration-resistant prostate cancer, or CRPC, is an aggressive stage of prostate cancer (PCa) in which PCa cells invade nearby or other parts of the body. When a patient with PCa goes through androgen deprivation therapy (ADT) and the cancer comes back or worsens, this is called CRPC. Instead of androgen-dependent signalling, recent studies show the involvement of the estrogen pathway through the regulation of estrogen receptor alpha (ERα) and estrogen receptor beta (ERß) in CRPC development. Reduced levels of testosterone due to ADT lead to low ERß functionality in inhibiting the proliferation of PCa cells. Additionally, ERα, which possesses androgen independence, continues to promote the proliferation of PCa cells. The functions of ERα and ERß in controlling PCa progression have been studied, but further research is needed to elucidate their roles in promoting CRPC. Finding new ways to treat the disease and stop it from becoming worse will require a clear understanding of the molecular processes that can lead to CRPC. The current review summarizes the underlying processes involving ERα and ERß in developing CRPC, including castration-resistant mechanisms after ADT and available medication modification in mitigating CRPC progression, with the goal of directing future research and treatment.

Therapeutic Potential of Hibiscus sabdariffa Linn. in Attenuating Cardiovascular Risk Factors.

Cardiovascular diseases (CVDs) represent a broad spectrum of diseases afflicting the heart and blood vessels and remain a major cause of death and disability worldwide. CVD progression is strongly associated with risk factors, including hypertension, hyperglycemia, dyslipidemia, oxidative stress, inflammation, fibrosis, and apoptosis. These risk factors lead to oxidative damage that results in various cardiovascular complications including endothelial dysfunctions, alterations in vascular integrity, the formation of atherosclerosis, as well as incorrigible cardiac remodeling. The use of conventional pharmacological therapy is one of the current preventive measures to control the development of CVDs. However, as undesirable side effects from drug use have become a recent issue, alternative treatment from natural products is being sought in medicinal plants and is gaining interest. Roselle (Hibiscus sabdariffa Linn.) has been reported to contain various bioactive compounds that exert anti-hyperlipidemia, anti-hyperglycemia, anti-hypertension, antioxidative, anti-inflammation, and anti-fibrosis effects. These properties of roselle, especially from its calyx, have relevance to its therapeutic and cardiovascular protection effects in humans. This review summarizes the findings of recent preclinical and clinical studies on roselle as a prophylactic and therapeutic agent in attenuating cardiovascular risk factors and associated mechanisms.

Role of Polyphenol in Regulating Oxidative Stress, Inflammation, Fibrosis, and Apoptosis in Diabetic Nephropathy.

Diabetic Nephropathy (DN) is known as one of the driving sources of End-Stage Renal Disease (ESRD). DN prevalence continues to increase in every corner of the world andthat has been a major concern to healthcare professionals as DN is the key driver of Diabetes Mellitus (DM) morbidity and mortality. Hyperglycaemia is closely connected with the production of Reactive Oxygen Species (ROS) that cause oxidative stress response as well as numerous cellular and molecular modifications. Oxidative stress is a significant causative factor to renal damage, as it can activate other immunological pathways, such as inflammatory, fibrosis, and apoptosis pathways. These pathways can lead to cellular impairment and death as well as cellular senescence. Natural substances containing bioactive compounds, such as polyphenols, have been reported to exert valuable effects on various pathological conditions, including DM. The role of polyphenols in alleviating DN conditions has been documented in many studies. In this review, the potential of polyphenols in ameliorating the progression of DN via modulation of oxidative stress, inflammation, fibrosis, and apoptosis, as well as cellular senescence, has been addressed. This information may be used as the strategies for the management of DN and development as nutraceutical products to overcome DN development.

The Role of Anthocyanin in Modulating Diabetic Cardiovascular Disease and Its Potential to Be Developed as a Nutraceutical.

Cardiovascular disease (CVD) is directly linked to diabetes mellitus (DM), and its morbidity and mortality are rising at an alarming rate. Individuals with DM experience significantly worse clinical outcomes due to heart failure as a CVD consequence than non-diabetic patients. Hyperglycemia is the main culprit that triggers the activation of oxidative damage, inflammation, fibrosis, and apoptosis pathways that aggravate diabetic CVD progression. In recent years, the development of phytochemical-based nutraceutical products for diabetic treatment has risen due to their therapeutic properties. Anthocyanin, which can be found in various types of plants, has been proposed for preventing and treating various diseases, and has elicited excellent antioxidative, anti-inflammation, anti-fibrosis, and anti-apoptosis effects. In preclinical and clinical studies, plants rich in anthocyanin have been reported to attenuate diabetic CVD. Therefore, the development of anthocyanin as a nutraceutical in managing diabetic CVD is in demand. In this review, we unveil the role of anthocyanin in modulating diabetic CVD, and its potential to be developed as a nutraceutical for a therapeutic strategy in managing CVD associated with DM.

Knowledge Gap in Understanding the Steroidogenic Acute Regulatory Protein Regulation in Steroidogenesis Following Exposure to Bisphenol A and Its Analogues.

The use of bisphenols has become extremely common in our daily lives. Due to the extensive toxic effects of Bisphenol A (BPA), the industry has replaced this endocrine-disrupting chemical (EDC) with its analogues, which have been proven to decrease testosterone levels via several mechanisms, including targeting the steroidogenic acute regulatory (StAR) protein. However, when exposed to BPA and its analogues, the specific mechanism that emerges to target StAR protein regulations remains uncertain. Hence, this review discusses the effects of BPA and its analogues in StAR protein regulation by targeting cAMP-PKA, PLC-PKC, EGFR-MAPK/ERK and Ca2+-Nur77. BPA and its analogues mainly lead to decreased LH in blood and increased ERK expression and Ca2+ influx, with no relationship with the StAR protein regulation in testicular steroidogenesis. Furthermore, the involvement of the cAMP-PKA, PLC-PKC, and Nur77 molecules in StAR regulation in Leydig cells exposed to BPA and its analogues remains questionable. In conclusion, although BPA and its analogues have been found to disrupt the StAR protein, the evidence in connecting the signaling pathways with the StAR regulations in testicular steroidogenesis is still lacking, and more research is needed to draw a solid conclusion.

Paternal Fenitrothion Exposures in Rats Causes Sperm DNA Fragmentation in F0 and Histomorphometric Changes in Selected Organs of F1 Generation.

The adverse effects of maternal pesticides exposure on the progeny is very well established. However, the impact of paternal exposure to pesticides such as Fenitrothion (FNT) on the histomorphometry of progeny's organs in unexposed mothers are much less well studied. Therefore, this study aims to evaluate the effects of paternal FNT exposure on the sperm quality of the parent rat and its effects on the histomorphometry of the progeny's organs. Randomly, male Sprague Dawley rats (n = 24) categorized as F0 were distributed equally into three groups namely Control, FNT-10, and FNT-20. Control received 1 mL/kg corn oil while FNT-10 and FNT-20 received 10 mg/kg and 20 mg/kg of FNT, respectively, via oral force feeding for 28 consecutive days. At the end of the study, male rats were mated with unexposed female rats and the male rats were sacrificed to obtain sperm for sperm characterization and DNA damage evaluation. Meanwhile, the rats' progeny (F1) namely pControl, pFNT-10, and pFNT-20 were left to grow until postnatal day 70 before being sacrificed to obtain the matured organs for histology and morphometric analysis. Our results showed that both doses of FNT reduced sperm quality and caused DNA fragmentation in F0 rats compared with the control group (p < 0.05). The number of Leydig cells as well as the diameter of the seminiferous tubules and glomerulus of the pFNT-20 group had significantly decreased (p < 0.05) compared with the pControl group. The Bowman's space of the pFNT-20 group had significantly increased (p < 0.05) compared with the pFNT-10 and pControl groups. Therefore, paternal exposure to FNT reduced the sperm quality and increased sperm DNA fragmentation in F0 male Sprague Dawley rats and altered the histology and morphometry of the selected organs in the F1 progeny.

Bisphenol A and Its Analogues Deteriorate the Hormones Physiological Function of the Male Reproductive System: A Mini-Review.

BPA is identified as an endocrine-disrupting chemical that deteriorates the physiological function of the hormones of the male reproductive system. Bisphenol F (BPF), bisphenol S (BPS), and bisphenol AF (BPAF) are actively explored as substitutes for BPA and are known as BPA analogues in most manufacturing industries. These analogues may demonstrate the same adverse effects as BPA on the male reproductive system; however, toxicological data explaining the male reproductive hormones' physiological functions are still limited. Hence, this mini-review discusses the effects of BPA and its analogues on the physiological functions of hormones in the male reproductive system, focusing on the hypothalamus-pituitary-gonad (HPG) axis, steroidogenesis, and spermatogenesis outcomes. The BPA analogues mainly show a similar negative effect on the hormones' physiological functions, proven by alterations in the HPG axis and steroidogenesis via activation of the aromatase activity and reduction of spermatogenesis outcomes when compared to BPA in in vitro and in vivo studies. Human biomonitoring studies also provide significant adverse effects on the physiological functions of hormones in the male reproductive system. In conclusion, BPA and its analogues deteriorate the physiological functions of hormones in the male reproductive system as per in vitro, in vivo, and human biomonitoring studies.

Monosodium glutamate daily oral supplementation: study of its effects on male reproductive system on rat model.

Monosodium glutamate (MSG) is widely used in food preparation industry and has been consumed regularly. Previous studies had reported on effects of MSG when given at extremely high dosages, the results are not applicable to human equivalent intake. Therefore, the present study aimed to evaluate the effect of MSG on sperm quality and changes in reproductive organs of adult male rats when taken at average human daily intake (ADI). Twenty-four adult male rats were randomly assigned into three groups; NC (Normal control), MSG60 and MSG120 where MSG was given orally at 60 mg/kg and 120 mg/kg to each respective group. All treatments were conducted for 28 consecutive days. MSG at estimated ADI of 120 mg/kg body weight resulted in a significant drop in sperm quality (p < 0.05) when compared to both control and MSG60 groups. A significant decrease in the weight of reproductive organs was also apparent (p < 0.05). Moreover, oxidative status evaluation showed that treatment of MSG induces oxidative stress in the testis, more severely at a dose of 120 mg/kg body weight. These findings are supported by alterations in the observed histology of reproductive organs. This study shows that an intake dose of 120 mg/kg body weight MSG could cause significant damage to the reproductive system. Abbreviations: MSG: Monosodium glutamate; ADI: average daily intake; PUFA: polyunsaturated fatty acid; FSH: follicle stimulating hormone; LH: luteinizing hormone; TCA: tricarbocylic acid; PF: prostatic fluid.

Fenitrothion alters sperm characteristics in rats: ameliorating effects of palm oil tocotrienol-rich fraction.

Exposure to organophosphate insecticides such as fenitrothion (FNT) in agriculture and public health has been reported to affect sperm quality. Antioxidants may have a potential to reduce spermatotoxic effects induced by organophosphate. The present study was carried out to evaluate the effects of palm oil tocotrienol-rich fraction (TRF) in reducing the detrimental effects occurring in spermatozoa of FNT-treated rats. Adult male Sprague-Dawley rats were divided into four equal groups: a control group and groups of rats treated orally with palm oil TRF (200 mg/kg), FNT (20 mg/kg) and palm oil TRF (200 mg/kg) combined with FNT (20 mg/kg). The sperm characteristics, DNA damage, superoxide dismutase (SOD) activity, and levels of reduced glutathione (GSH), malondialdehyde (MDA), and protein carbonyl (PC) were evaluated. Supplementation with TRF attenuated the detrimental effects of FNT by significantly increasing the sperm counts, motility, and viability and decreased the abnormal sperm morphology. The SOD activity and GSH level were significantly increased, whereas the MDA and PC levels were significantly decreased in the TRF+FNT group compared with the rats receiving FNT alone. TRF significantly decreased the DNA damage in the sperm of FNT-treated rats. A significant correlation between abnormal sperm morphology and DNA damage was found in all groups. TRF showed the potential to reduce the detrimental effects occurring in spermatozoa of FNT-treated rats.

Pre-Initiation Effect of Oleuropein towards Apoptotic and Oxidative Stress Levels on the Early Development of Two-Stage Skin Carcinogenesis.

Background: Oleuropein is a form of phenoliccompound which can be majorly found in the oliveleaves. Previous studies have shown several biologicalfunctions of oleuropein against different cancer cells.Aim and Objectives: This research was designed tostudy the pre-initiation effect of oleuropein on the earlyskin tumour development using a mouse model.Material and Methods: Female Institute of CancerResearch (ICR) mice (n=6 per group) were divided into2 groups (group 1 as a carcinogen control and group 2 asa vehicle control) and 1 treatment group (group 3: 10mg/kg of oleuropein). Results:After 10 weeks, Group 3showed delay in epidermal hyperplasia formation and asignificant reduction (p<0.05) in the epidermalthickness as compared to Group 1. Data were alsodisplayed a significant increase (p<0.05) in theapoptotic rate in Group 3 as compared to Group 1 and 2.For biochemical assays, the level of Malondialdehyde(MDA) was significantly (p<0.05) decreased whilst thelevels of Glutathione (GSH) and Superoxide Dismutase(SOD) were significantly (p<0.05) increased in Group 3as compared to Group 1. Conclusion: Our resultsindicate that pre-initiation treatment of oleuropein mayprevent skin tumour development through itsantioxidant and apoptotic activities.

Fenitrothion induced oxidative stress and morphological alterations of sperm and testes in male Sprague-Dawley rats.

OBJECTIVE: Fenitrothion residue is found primarily in soil, water and food products and can lead to a variety of toxic effects on the immune, hepatobiliary and hematological systems. However, the effects of fenitrothion on the male reproductive system remain unclear. This study aimed to evaluate the effects of fenitrothion on the sperm and testes of male Sprague-Dawley rats. METHODS: A 20 mg/kg dose of fenitrothion was administered orally by gavages for 28 consecutive days. Blood sample was obtained by cardiac puncture and dissection of the testes and cauda epididymis was performed to obtain sperm. The effects of fenitrothion on the body and organ weight, biochemical and oxidative stress, sperm characteristics, histology and ultrastructural changes in the testes were evaluated. RESULTS: Fenitrothion significantly decreased the body weight gain and weight of the epididymis compared with the control group. Fenitrothion also decreased plasma cholinesterase activity compared with the control group. Fenitrothion altered the sperm characteristics, such as sperm concentration, sperm viability and normal sperm morphology, compared with the control group. Oxidative stress markers, such as malondialdehyde, protein carbonyl, total glutathione and glutathione S-transferase, were significantly increased and superoxide dismutase activity was significantly decreased in the fenitrothion-treated group compared with the control group. The histopathological and ultrastructural examination of the testes of the fenitrothion-treated group revealed alterations corresponding with the biochemical changes compared with the control group. CONCLUSION: A 20 mg/kg dose of fenitrothion caused deleterious effects on the sperm and testes of Sprague-Dawley rats.

Tocotrienol rich fraction prevents fenitrothion induced pancreatic damage by restoring antioxidant status.

Fenitrothion (FNT) is extensively used as pesticide and may induce oxidative stress in various organs. Tocotrienol, a form of vitamin E found in palm oil, reduces oxidative impairments in pathological conditions. This study aims to investigate the effects of palm oil tocotrienol rich fraction (TRF) on fenitrothion-induced oxidative damage in rat pancreas. Forty male Sprague-Dawley rats were divided into four groups: control group, FNT group, TRF group and FNT+TRF group. Regimens FNT (20 mg kg(-1) b.wt.) and TRF (200 mg kg(-1) b.wt.) were force-fed for 28 consecutive days with control group only receiving corn oil. Chronic administration of fenitrothion significantly (p < 0.05) induced oxidative damage in pancreas of rats with elevated malondialdehyde and protein carbonyl level. Depletion of glutathione and significant (p < 0.05) reduction in antioxidant enzyme activities in pancreas homogenate additionally suggested induction of oxidative stress. Despite these changes in pancreas of intoxicated rats, no significant (p < 0.05) changes in blood glucose and pancreas histology were observed. Co-administration of FNT with TRF alleviated these oxidative changes and significantly (p < 0.05) restored antioxidant status. Enzymatic activities of Superoxide Dismutase (SOD) and Catalase (CAT) were normalized. In conclusion, tocotrienol rich fraction of palm oil prevents fenitrothion-induced pancreatic oxidative damage in rats.