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Abstract The present work is conducted to test alleviation of toxic hazardous influence of acetaminophen by Ginkgo biloba extract. Therefore this work was designed to study the effects of acetaminophen, Ginkgo biloba and combination of both together on serum biochemical parameters (liver function, kidney function, total lipids and glucose), some antioxidants (glutathione, glutathione peroxidase, catalase and superoxide dismutase) as well as MDA as a marker for lipid peroxidation. The study was performed on male albino rats, weighing 100-120g. The experiments were divided into two parts; each part is divided into four groups: Part I: Acute Study 1- Animals of the first group received (i.p.) saline solution and served as control group. 2- Animals of the second group received (i.p.) single doses of (50 mg/kg) extracted Ginkgo biloba and served as EGB group. 3- Animals of the third group received (i.p.) single doses of (900 mg/kg) acetaminophen and served as AAP group. 4- Animals of the fourth group received (i.p.) single doses of (900 mg/kg AAP +50 mg/kg EGB) and served as AAP + EGB group. Animals of the different experimental group were decapitated 4 hours after treatments. Part II: Subchronic Study Subchronically-treated groups were divided into 8 groups. Animals of group1 received (i. p.) saline solution daily for 1 week and served as controls. Animals of group 2 were treated with Ginkgo biloba extract (GBE) (50 mg /kg b. wt) for 1 week. Animals of group 3 were treated for 1 week with AAP (250 mg/kg b. wt.). Animals of group 4 were treated for 1 week with GBE (50 mg /kg b. wt) and AAP (250 mg/kg b. wt.). As for groups 5, 6, 7 and 8, they were treated experimentally as groups 1, 2, 3 and 4 but for 2 weeks. Body weight: There was a non-significant decrease in body weight in acetaminophen and Ginkgo biloba group compared to the control group but liver and kidney weights in acetaminophen group showed a significant decrease in comparison with control group after two weeks of administration. A) Biochemical studies: 1- Liver Function: I- Alanine aminotransferase (ALT): The treatment with acetaminophen only caused significant increase (p<0.05) in ALT level in comparison with control group. The combination of acetaminophen with Ginkgo biloba resulted in nonsignificant increase in ALT concentration which implies that G. biloba reduce the toxic influence of acetaminophen on the liver. II- Aspartate aminotransferase (AST): It has been found that serum AST activity in acetaminophen group significantly increased in comparison with the control group. In addition, the results did not show any significant changes between Ginkgo biloba group and the control group during the experimental periods. III-Alkaline phosphatase: Serum alkaline phosphatase value was increased in acetaminophen group in comparison with the control group. In addition, it was found that serum alkaline phosphatase in Ginkgo biloba group and Ginkgo biloba and acetaminophen group slightly changed when compared to the control group. IV- Albumin: In the present study, serum albumin was significantly decreased in acetaminophen group compared to the control group. However, coadministration of acetaminophen and Ginkgo biloba resumed the control level of albumin. V- Bilirubin: Serum bilirubin was increased in acetaminophen group but it showed a non-significant change in Ginkgo biloba group in comparison with the control group. The results revealed that acetaminophen – Ginkgo biloba combination did not cause a significant change in serum bilirubin level after four hours, one and two weeks of administration from the control group. 2-KidneyFunction: I- Creatinine: There was a significant increase in serum creatinine after administration of acetaminophen only in comparison with the control group. Animals treated with both Ginkgo biloba and acetaminophen showed non-significant change in serum creatinine in comparison with the control group. II- Urea: Serum urea (mg/dl) in acetaminophen group was significantly increased and the data were statistically significant compared to the control group. Serum urea in Ginkgo biloba group and control group did not show any significant change when compared statistically. It has been found that serum urea in Ginkgo biloba and acetaminophen group was slightly different from the control group but the data did not show significant difference. III- Uric acid: Serum uric acid was significantly increased in acetaminophen group compared to the control group, while the lowest decrease in serum uric acid was observed in Ginkgo biloba group after four hours, ane and two weeks of administration. Different metabolites: I- Glucose. II- Total lipids. III- Total cholesterolIV- HDL. V- LDL. VI- VLDL. VII- triglycerides. I- Glucose: Serum glucose increased in acetaminophen group compared to the control group. Serum glucose in Ginkgo biloba group and Ginkgo biloba and acetaminophen group did not show any significant change when compared to the control group. II- Total lipids: In Ginkgo biloba and acetaminophen group there was an improvement in the level of serum total lipids compared to its value in acetaminophen group. Total lipids in acetaminophen group were significantly increased when compared to the control group. III - Total cholesterol: Serum total cholesterol was increased in acetaminophen group compared to control group but in Ginkgo biloba group total cholesterol was slightly different from its value in the control group. Serum total cholesterol levels in Ginkgo biloba and acetaminophen group was higher than its value in control group but it did not show a significant difference. IV- High – density Lipoprotein (HDL): There was a significant decrease in serum HDL after administration of acetaminophen only in comparison with the control group. Serum HDL showed non- significant change in Ginkgo biloba and acetaminophen in comparison with the control group. V- Low – density Lipoprotein (LDL): Serum low-density lipoprotein (LDL) was increased in acetaminophen group, however its values in Ginkgo biloba and acetaminophen group slightly increased as compared to the control group but this increase was significantly different from the control group around the experimental period. VI- Very low – density lipoprotein (VLDL): Serum very low-density lipoprotein was increased in acetaminophen group when compared to control group but serum VLDL in other groups was slightly changed compared to the control group after four hours, one and two weeks of drug administration. VII- Triglycerides: Serum triglycerides in Ginkgo biloba and acetaminophen group were increased compared to the control group but they did not show a significant difference. Serum triglycerides after two weeks of administration was increased in all treatment groups compared to their values after one week. 3- Antioxidants: I -Glutathione: Only acetaminophen treatment caused a significant (P<0.05) decrease in liver reduced glutathione after four hours, one week and two weeks of administration in comparison with the control group. II - Glutathione peroxidase: Liver glutathione peroxidase decreased in acetaminophen group compared to the control group but liver glutathione peroxidase in Ginkgo biloba group did not show any significant changes from the control group. III- Glutathione S- transferase (GST): A non-significant increase in glutathione S- transferase activity were detected by the GBE treatment, but the significantly decrease in GST activity was observed in rat liver after treatment with acetaminophen. IV- Catalase: Liver catalase in Ginkgo biloba group and Ginkgo biloba and acetaminophen group did not show a significant change when compared to the control group after one and two weeks of administration. V- Superoxide dismutase: Liver superoxide dismutase activity significantly decreased in acetaminophen group when compared to the control group. Liver superoxide dismutase in Ginkgo biloba and Ginkgo biloba and acetaminophen group did not show a significant change in comparison with control group after 1 and 2 weeks of treatment. 4- Malondialdehyde as a marker for lipid peroxidation: Liver malondialdehyde were significantly increased in acetaminophen group compared to the control group around the experimental period. B- Histopathological studies: Liver sections from rats administrated acetaminophen showed many pathological alterations, slight congestion of hepatic sinusoids, cytoplasmic vacoulizations of hepatocytes and sinusoidal leukocytosis, Kupffer cells activation, vacuolations and congestion of capillary tufts as well as vacuolations of epithelial lining of renal tubules. It has been found that an improvement occurred in liver after administration of both Ginkgo biloba and acetaminophen where rats exhibited little pathological alterations, slight congestion of hepatic sinusoids, and congestion of central veins. Kidney sections from rats administrated acetaminophen showed many pathological alteration, vacuolations of epithelial lining of renal tubules and congestion of blood capillary. However, it has been found that, an improvement has been happened in kidney after administration of both Ginkgo biloba and acetaminophen. In conclusion, it was found, in this work, that Ginkgo biloba has a protective effect against hepatotoxicity induced by acetaminophen in rats as it participated in a melioration of the effects exerted by acetaminophen on biochemical and histological changes observed in this study. |