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Oral administration of Nigella sativa oil attenuates arsenic-induced redox imbalance,DNA damage,metabolic distress,and histopathological alterations in rat intestine
Institution:1. Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, U.P., India;2. Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, U.P., India;1. Department of Biomedical Engineering, Iskenderun Technical University, Hatay 31200, Turkey;2. Department of Genetics, Inonu University School of Medicine, Malatya 44280, Turkey;3. Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir 35430, Turkey;1. Department of Pathological Physiology, Faculty of Medicine, University of Belgrade, Dr Subotica1, 11000 Belgrade, Serbia;2. University Children’s Hospital, Tir?ova 10, 11000 Belgrade, Serbia;3. Institute of Meat Hygiene and Technology, Ka?anskog 13, 11000 Belgrade, Serbia;4. Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Dr Subotica 15, 11000 Belgrade, Serbia;1. Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China;2. Department of Clinical Laboratory, Binzhou Medical University Hospital, Binzhou 256603, PR China;3. National Center for Orthopaedics, Department of Molecular Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing 100035, PR China;4. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China;5. College of Veterinary Medicine, China Agricultural University, Beijing 100083, PR China;6. State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medicine Sciences & School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100005, PR China;1. Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, PO Box 7607, Makkah, Saudi Arabia;2. Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, PO Box 7607, Makkah, Saudi Arabia;3. Clinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt;4. Biochemistry Department, Faculty of Pharmacy, Al-Azhar University, Assuit 71524, Egypt;1. Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China;2. Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, Taiyuan, Shanxi 030001, China;3. Key Lab of Cellular Physiology of Education Ministry, Shanxi Medical University, Taiyuan, Shanxi 030001, China;4. Department of Anatomy, Shanxi Medical University, Taiyuan, Shanxi 030001, China;1. Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410078, China;2. Center of Clinical Pharmacology, the Third Xiangya Hospital, Central South University, Changsha 410013, China;3. Environmental Science and Engineering, College of Resource and Environment, Hunan Agricultural University, Changsha 410128, China
Abstract:BackgroundExposure to arsenic, a widespread environmental toxin, produces multiple organ toxicity, including gastrointestinal toxicity. Nigella sativa (NS) has long been revered for its numerous health benefits under normal and pathological states. In view of this, the present study attempts to evaluate the protective efficacy of orally administered Nigella sativa oil (NSO) against arsenic-induced cytotoxic and genotoxic alterations in rat intestine and elucidate the underlying mechanism of its action.MethodsRats were categorized into the control, NaAs, NSO, and NaAs+NSO groups. After pre-treatment of rats in the NaAs+NSO and NSO groups daily with NSO (2 ml/kg bwt, orally) for 14 days, NSO treatment was further continued for 30 days, with and without NaAs treatment (5 mg/kg bwt, orally), respectively. Various biochemical parameters, such as enzymatic and non-enzymatic antioxidants, carbohydrate metabolic and brush border membrane marker enzyme activities were evaluated in the mucosal homogenates of all the groups. Intestinal brush border membrane vesicles (BBMV) were isolated, and the activities of membrane marker enzyme viz. ALP, GGTase, LAP, and sucrase were determined. Further, the effect on kinetic parameters viz KM (Michaelis-Menten constant) and Vmax of these enzymes was assessed. Integrity of enterocyte DNA was examined using the comet assay. Histopathology of the intestines was performed to evaluate the histoarchitectural alterations induced by chronic arsenic exposure and/or NSO supplementation. Arsenic accumulation in the intestine was studied by inductively coupled plasma-mass spectroscopy (ICP-MS).ResultsNaAs treatment caused substantial changes in the activities of brush border membrane (BBM), carbohydrate metabolism, and antioxidant defense enzymes in the intestinal mucosal homogenates. The isolated BBM vesicles (BBMV) also showed marked suppression in the marker enzyme activities. Severe DNA damage and mucosal arsenic accumulation were observed in rats treated with NaAs alone. In contrast, oral NSO supplementation significantly alleviated all the adverse alterations induced by NaAs treatment. Histopathological examination supported the biochemical findings.ConclusionNSO, by improving the antioxidant status and energy metabolism, could significantly alter the ability of the intestine to protect against free radical-mediated arsenic toxicity in intestine. Thus, NSO may have an excellent scope in managing gastrointestinal distress in arsenic intoxication.
Keywords:Sodium arsenate  Gastrointestinal toxicity  Oxidative stress  Carbohydrate metabolism
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