Antioksidan morinin 7,12-dimetilbenz[a]antrasen ve endosülfana maruz bırakılmış sağlıklı ve streptozotosin indüklenmiş diyabetik sıçanların karaciğerinde ksenobiyotik metabolize eden enzimler üzerine etkileri

Living organisms are exposed to different chemicals at the same time in their daily lives. Some of these chemicals are beneficial but some of them are harmful for us. 7,12-Dimethylbenz[a]anthracene (DMBA) is a lipid soluble molecule, producing toxic and carcinogenic effects within the body. Endosulfan is an organochlorine pesticide, used extensively in the agricultural areas against insects. It may exist in air, freshwater, sea water, soil samples and foods. It is possible to be exposed both DMBA and endosulfan with smoking cigarette and breathing polluted air in our daily lives. Morin is a dietary flavonoid having chemoprotective and antioxidant properties in living organisms. Diabetes mellitus is a metabolic disorder causing damage in organs. The effects of morin have not been determined in the presence of toxic chemicals and diabetes. Therefore, this study is aimed to determine the effect of morin on xenobiotic metabolizing enzymes in the presence of DMBA and endosulfan in normal and diabetic rats. For this purpose 120 male Wistar rats (weighing 170-245 g) were randomly selected and divided into 16 groups (8 groups were composed of normal rats and the other 8 groups were diabetic rats). The rats in control group were treated with corn oil three times in a week. Morin administration was started at 1st day of the administration period and continued through the experimental period with 25 mg/kg body weight morin with the frequency of three times in a week. DMBA-treated groups were gavaged with 30 mg/kg body weight DMBA at 12th, 19th and 26th days of the administration period. Endosulfan treatment was started at the 12th day of the administration period at a dose of 5 mg/kg body weight endosulfan. This treatment was continued through the experimental period with the frequency of three times in a week. Rats in normal rat groups were killed by cervical dislocation on the 54th day of the administration period and rats in diabetic rat groups were killed by cervical dislocation on the 43rd day of the administration period. Microsomes and cytosols were prepared for each liver tissue by differential centrifugation. Cytochrome P4501A1 (CYP1A1) associated 7-ethoxyresorufin O-deethylase (EROD) activities increased in all treatment groups. Rats in morin, DMBA and endosulfan group had 1.6, 1.8 and 1.6 fold higher EROD activities than those of the control group. The highest EROD activities measured in liver microsomes of normal rats were obtained from DMBA+endosulfan+morin group which was significantly higher (2.6-fold) than the activity obtained from the control group (p<0.05). Cytochrome P4501A2 associated 7-methoxyresorufin O-demethylase (MROD) activities of endosulfan, morin and endosulfan+morin groups were not different from the MROD activities of the control. DMBA treatment significantly increased MROD activity in normal rats (1.5-fold). Co-administration of DMBA and endosulfan also increased MROD activities in normal rat group (1.8-fold). Morin treatment decreased the effect of endosulfan and DMBA on MROD activity. Morin, endosulfan and DMBA treatments did not produce significant effect on cytochrome P4502B associated 7-pentoxyresorufin O-depentylase (PROD) activities in normal rat groups. Cytochrome P4502E associated aniline 4-hydroxylase activities of rats significantly increased with endosulfan and DMBA administration. Their effects on CYP2E decreased with administration of these chemicals with morin. Cytochrome P4503A associated erythromycin N-demethylase activities increased with endosulfan, DMBA and morin treatment. The highest activities were measured in DMBA+endosulfan+morin group in normal rats. Glutathione S-transferase activities increased in DMBA treated groups. Catalase and glutathione reductase activities were not affected from morin and endosulfan treatments. DMBA treatment significantly increased catalase and glutathione reductase activities. The induction of the diabetes mellitus by intraperitoneal injection of streptozotocin significantly increased EROD, MROD, PROD, erythromycin N-demethylase, glutathione S-transferase, catalase and glutathione reductase activities of rat liver microsomes and cytosols compared to the control group (p<0.05). Endosulfan and DMBA treatments increased EROD and MROD activities in diabetic rats. Morin treatment decreased EROD activities in endosulfan and DMBA treated diabetic rats. MROD activities increased with endosulfan and DMBA treatments in diabetic rats. Morin treatment decreased MROD activities in diabetic rats treated with endosulfan and DMBA. Aniline 4-hydroxylase, erythromycin N-demethylase, glutathione S-transferase and catalase activities decreased with endosulfan and DMBA treatments in diabetic rats. Besides the protein analysis, liver tissues were also evaluated by histopathological analysis. The histopathological studies indicated that morin treatment was not modified the appearance of the liver cell. Co-administration of endosulfan and DMBA increased tissue damage in the liver. Morin treatment reduced the endosulfan and DMBA induced liver tissue damages both in normal and diabetic rats. In conclusion, co-administration of morin with endosulfan and DMBA decreased the toxic effects of endosulfan and DMBA in normal and diabetic rats.