ABSTRACT
Methotrexate (MTX) and azathioprine (AZA) are chemotherapeutic, antimetabolic, and immunosuppressive agents with substantial risks such as oxidative lesions to the liver. This study examined the effect of grape seed extract (GSE; gervital) in attenuating hepatotoxicity caused by MTX or AZA treatment. Rats were divided into six groups (six rats per group): Group I, normal control group; Group II, GSE (150 mg/kg/day); Group III, MTX (8 mg/kg/week); Group IV, AZA (15 mg/kg/day); Group V, GSE (150 mg/kg/day) + MTX (8 mg/kg/week); and Group VI, GSE (150 mg/kg/day) + AZA (15 mg/kg/day). After 35-day experimental period, all rats were sacrificed and blood was collected for biochemical study and hemoglobin (Hb) assessment. The liver was weighed and triaged for histological, ultrastructural, and biochemical studies. MTX and AZA treatment decreased Hb levels, increased relative liver weight, increased the activity of glutamate pyruvate transaminase (ALT) and glutamate oxaloacetate transaminase (AST) aminotransferase (ALT) and aspartate aminotransferase (AST) values, and displayed histopathological and ultrastructural alterations. These changes included the disorganization of hepatocytes, pyknosis, karyolysis of some nuclei, and mononuclear leukocytic infiltration. The liver with significant oxidative stress (OS) showed decreased reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and increased malondialdehyde (MDA) levels. In contrast, GSE administration ameliorated ALT, AST, and all histopathological and ultrastructural changes. GSE treatment also reduced MDA levels but increased the antioxidant parameters. In conclusion, it was concluded that GSE supplementation could be considered as a promising antioxidant in reducing OS, histopathological and ultrastructural alterations induced by MTX and AZA.
Subject(s)
Azathioprine , Chemical and Drug Induced Liver Injury , Grape Seed Extract , Methotrexate , Animals , Antioxidants/metabolism , Aspartate Aminotransferases/metabolism , Azathioprine/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolism , Glutamates/metabolism , Grape Seed Extract/pharmacology , Liver , Methotrexate/toxicity , Oxidative Stress , Rats , Rats, WistarABSTRACT
BACKGROUND: Most guidelines all over the world recommended metformin as the first-line treatment for in type 2 diabetic patients. Therefore, the present study was suggested to assess the outcome of metformin administration and glycemic status on alterations in red blood cell (RBCs) indices as well as the oxidative stress in type 2 diabetic patients. METHODS: Between December 2016 and October of 2017, a total of 158 eligible individuals were classified as 50 healthy subjects and 108 diabetic patients who were subdivided into six groups according to the type of anti-diabetic treatments. RESULTS: Overall, the results elucidated that hemoglobin concentration was markedly diminished, while red cell distribution width (RDW) value was significantly (P < 0.001) elevated in all diabetic groups as compared to control. Moreover, in all diabetic groups, malondialdehyde (MDA) concentration was elevated noticeably (P < 0.001), while reduced glutathione (GSH) revealed a lower concentration (P < 0.001) than that of control. CONCLUSION: The present study exhibited the amelioration effect of metformin administration on oxidative stress and glycemic status which reflected on some RBCs indices. However, hemoglobin concentration showed a noticeable diminution in all metformin-treated groups in spite of the improvement in glycemic and oxidative stress status which indicated that the metformin-induced anemia is independently from diabetic complications.
