Tramadol has become the most prescribed opioid worldwide. In this study, we investigate the chronic tramadol toxicity on liver, kidney and brain through analysis of the biochemical, histopathological and immunohistochemical findings in albino rats. This work included two groups; the first group served as control (n = 20 rats) and received saline solution only orally along the study. The second group received oral doses of tramadol HCl (n = 20 rats) suspended in saline solution equal to 60 mg/kg/daily for 90 days. After sacrifice biochemical evaluation of liver function (ALT: alanine transaminase, AST: aspartate transaminase, LDH: Lactate dehydrogenase), kidney function (BUN: blood urea nitrogen, creatinine), oxidative stress markers (Malondialdehyde (MDA) in liver and kidney) and total antioxidant capacity (TAC) was carried out followed by histopathological and immunohistochemical examination of liver, kidney and brain. Highly significant elevation in serum ALT, AST and LDH in the tramadol group was detected in comparison with the control group. Moreover, there was highly significant elevation of MDA in liver and kidney and serum TAC in the tramadol group compared to the control. Histopathological examination of the liver, kidney and brain showed various changes in Bcl2 expression. It was decreased in the organs of the tramadol group and was more obvious in brain. Chronic usage of tramadol has toxic effects on liver and kidney as indicated by biochemical elevation of enzymes and histopathological changes. Moreover, tramadol mainly affected the brain as the histopathology showed marked hypercellularity, disarrangement of nerve cells and irregular shrunken neurons. Tramadol also induced apoptosis as indicated by the decrease in the protective anti apoptotic antigen Bcl2.
View Full Article