Bisphenol A‑Induced Oxidative Damage in the Hepatic and Cardiac Tissues of Rats: the Modulatory Role of Sesame Lignans
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EXPERIMENTAL AND THERAPEUTIC MEDICINE 19: 33-44, 2020 Bisphenol A‑induced oxidative damage in the hepatic and cardiac tissues of rats: The modulatory role of sesame lignans SABER M. EWEDA1,2, AL SAYEDA A. NEWAIRY1, HEBA M. ABDOU3 and ASSMAA S. GABER1 1Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Medina 42353, Kingdom of Saudi Arabia; Departments of 2Biochemistry and 3Zoology, Faculty of Science, Alexandria University, Alexandria 21561, Egypt Received April 27, 2018; Accepted May 31, 2019 DOI: 10.3892/etm.2019.8193 Abstract. Bisphenol A (BPA) is an environmental pollutant Introduction that is widely produced throughout the world. It is primarily used in the manufacture of polycarbonate plastics, epoxy Bisphenol A [BPA; 2,2-bis (4-hydroxyphenyl)], an environ- resins, paints and dental materials. BPA has been reported to mental contaminant, is an increasingly produced worldwide promote hepatotoxicity and cardiotoxicity. The antioxidant chemical (1). BPA is used in the manufacture of polycarbonate activity of sesame lignans is well established. The current plastics, epoxy resins and hard plastic bottles, which are study assessed the protective efficiency of sesame lignans commonly consumed products (2). Epoxy resins are used in against BPA-induced hepatotoxicity and cardiotoxicity. Rats food-contact surface lacquer coatings for cans, automobile were divided into 4 groups: A control group, a BPA-treated parts and as a coating for PVC pipes (3). The increased use of group, a sesame lignans-treated group and a sesame lignans these products has led to a BPA content of >90% in various and BPA-treated group. Rats were orally administered their human biological fluids, including human breast milk, amni- respective doses daily [30 mg/kg body weight (BW) BPA otic fluid and neonatal blood (4). The primary route of BPA and/or 20 mg/kg BW sesame lignans] for 6 weeks. Liver func- exposure is via ingestion (1), but transdermal absorption and tion tests were performed using serum of all groups. Lipid inhalation are probable secondary exposure routes, particularly profile and antioxidant status were also measured in liver in individuals who work in companies that produce BPA-based tissue of the studied groups. The results were confirmed by products (3,5). BPA is an endocrine-disrupting substance with histopathological examination of liver and heart tissues. The estrogenic and thyroid hormone-like effects (6). Several studies oral administration of BPA was revealed to elicit significant have reported that BPA exposure promotes hepatotoxicity and decreases in the activities of hepatic glutathione peroxidase, induces oxidative damage via different mechanisms (7,8). glutathione reductase, superoxide dismutase and glutathione. Other studies have determined an association between BPA It also significantly increased levels of malondialdehyde. exposure and an increased risk of reproductive dysfunction, Furthermore, BPA-treatment resulted in lipid accumulation, cardiovascular disease, obesity, type II diabetes and thyroid elevated activities of alanine aminotransferase, creatine kinase dysfunction (6,9). Sesame (Sesamum indicum L.) is a crop MB and lactate dehydrogenase, and histological changes of that is produced worldwide. It has been cultivated in Asia and liver and heart tissues. However, the co-administration of Africa for its high content of edible oil and protein (10) and has sesame lignans and BPA attenuated hepatotoxicity, cardiotox- been used as a traditional food source in the countries of East icity and BPA-induced histological changes. The results of the Asia (11). Sesame oil is considered to be a superior vegetable current study indicated that sesame lignans may be helpful in oil, as it has a high nutritional value (12) that is therapeuti- the development of novel natural drugs to treat hepatic and cally effective within 3-12 h after oral administration (13). cardiovascular disorders. Sesame oil decreases blood pressure, lipid profiles and lipid peroxidation, and increases enzymatic and nonenzymatic antioxidants (14). The potent antioxidant activity of sesame oil is due to its high content of polyunsaturated fatty acids and lignans (15). Sesame lignans include sesamin, sesamolin, sesamol, sesaminol, sesamolinol, pinoresinol, matairesinol, Correspondence to: Dr Saber M. Eweda, Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, lariciresinol and episesamin, which all exhibit a broad Taibah University, Janadah Bin Umayyah Road, Medina 42353, spectrum of biological properties (16). Sesame lignans individ- Kingdom of Saudi Arabia ually or in combination, exhibit different biological activities. E-mail: [email protected] Sesamin has been revealed to serve an important role in lipid and glucose metabolism, hypertension, anti‑inflammation and Key words: sesame lignans, Bisphenol A, oxidative stress, liver, heart free radical scavenge (17). Sesamolin promotes apoptosis, suppresses neuronal reactive oxygen species (ROS) genera- tion and attenuates mutagenesis induced by H2O2 (18,19). 34 EWEDA et al: HEPATO- AND CARDIOPROTECTIVE EFFECTS OF SESAME LIGNANS Furthermore, sesaminol inhibits DNA oxidative damage, A control group (C-group), a BPA-treated group (B-group) decreases low-density lipoprotein (LDL) oxidation induced that received 30 mg/kg (24), a sesame lignans-treated group by copper and inhibits membrane lipid peroxidation (20,21). (S-group) that were treated with sesame lignans (20 mg/kg) (25) Yashaswini et al (22) reported that the oral administration of and a BPA plus sesame lignans-treated group (BS-group) that sesamol and sesamin modulates inflammatory and oxidative received BPA (30 mg/kg) and sesame lignans (20 mg/kg). damage markers in lipopolysaccharide (LPS)-injected rats. Rats were orally administered their respective doses daily for However, to the best of our knowledge, there are no in vivo 6 weeks. studies assessing the protective effect of sesame lignans against BPA-induced hyperlipidemia and oxidative damage. Sampling and tissue preparation. At the end of experimental Accordingly, the aim of the current study was to investigate period, rats were starved for 12 h and then deeply euthanized the modulative effects of sesame lignans against BPA-induced via an intraperitoneal injection of 100 mg/kg ketamine and hepatic and cardiac toxicity in rats. This was achieved by 20 mg/kg xylazine. The 12 h fasting period prior to sampling performing liver and heart function tests, determining lipid did not cause remarkable loss of body weight or any observed profiles and assessing the levels of certain oxidants and anti- adverse effects on rats. After euthanasia, 4 ml of blood was oxidants. Biochemical parameters were also confirmed via obtained through cardiac puncture using a sterile syringe. histopathological examinations of liver and heart tissue. In Death was subsequently confirmed by the inhalation of addition, the dorsal aorta was quantitatively analyzed. CO2 from a pressurized tank at a flow rate of 25% per min followed by cervical dislocation. Serum was obtained by Materials and methods centrifugation of clotted blood at 1,000 x g at 25˚C for 10 min and kept at ‑20˚C for lipid profiling and liver and heart func- Chemicals. BPA, glutathione reductase (GR), gluta- tion tests. Liver, heart and dorsal aorta were immediately thione (GSH), pyrogallol, NADPH, 2-thiobarbituric acid, isolated and washed with cold saline solution. Pieces of tissue 1,1,3,3-tetraethoxypropane, 5,5'-dithiobis-(2-nitrobenzoic were then fixed for 12 h with 10% formalin at 25˚C for histo- acid) (DTNB) and bovine serum albumin were purchased logical examination. Liver tissue (0.25 g) was subsequently from Sigma-Aldrich (Merck KGaA). All other general chemi- homogenized individually in 5 ml of 5% trichloroacetic acid, cals and kits were of analytical grade. containing 0.003 M EDTA. The homogenate was centrifuged at 500 x g for 15 min at 4˚C and the supernatants were stored Extraction and purification of sesame lignans.Sesame lignans at ‑20˚C for reduced GSH determination. Additionally, were extracted and purified as described by Reshma et al (23). 0.5 g liver tissue was isolated, washed and homogenized Sesame oil (100 g) was mixed with methanol (1:1 w/v) in an in PBS (0.1 M; pH 7.4). The homogenate was centrifuged extraction vessel. The mixture was then stirred for 10 min at at 25,000 x g for 10 min at 4˚C (Hitachi Ltd.; model, EBA 70˚C and transferred into a separating funnel. Following 15 min 12R). Supernatants were stored in aliquots of 1ml at ‑20˚C for of settling time, the methanolic extract was separated from subsequent biochemical analysis. the residual oil, which was subsequently stripped of solvent and subjected to 9 additional sequential extractions with fresh Extraction of hepatic total lipids. Total liver lipid content batches of methanol performed exactly as described above. was measured via gravimetric determination according to a The 10 methanolic extracts were pooled and concentrated via method previously described by Folch et al (26). Half gram of evaporation at 40˚C using a rotary evaporator (Model 4622; liver tissue was homogenized in 5 ml of chloroform-methanol BUCHI Rotavapor™ R‑100; Thermo Fisher Scientific, Inc.). mixture (2:1, v/v) using a Polytron homogenizer (model, TR-10; These extracts were then dispersed in petroleum ether at a Tekmar). The solvent obtained from the extract was evaporated ratio of 1:0.5 (w/v). The mixture was left to stand for