Histopathological and Molecular Studies on Tramadol Mediated Hepato-Renal Toxicity in Rats

Tramadol, a broadly used opioid in recent years, is an effective analgesic agent for the treatment of moderately severe acute or chronic pain. The liver and kidneys are responsible for the metabolism and excretion of opioids, which may cause hepatotoxicity and nephrotoxicity. The present study was designed to evaluate the toxic effects of tramadol on the liver and kidney of experimental rats. Twenty male albino rats, used in the present study, were divided into two groups; control and tramadol-treated (40 mg/kg b.w., orally) for 20 consecutive days. Livers and kidneys specimens were taken for histopathological, molecular and biochemical studies. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were determined in these tissues. Histopathological changes in liver and kidney were evaluated by light microscopy. Finally, RT-PCR technique was used to analysis the expression level of apoptosis-related genes, Bcl-2 and Bax, in liver and kidney tissues. Tramadol caused a significant reduction in the activities of GSH, SOD, and CAT, whilst a significant increase in the level of MDA in compared to control groups in both liver and kidney. In accordance with the biochemical findings, our data showed that tramadol treatment induced histopathological alterations in both tissues. These alterations were manifested by severe hydropic degeneration, with congested central veins of the liver and degenerated renal tubules and atrophied glomerulus. Moreover, mRNA expression level of proapoptotic marker Bax showed a significant increase, whereas the antiapoptotic Bcl-2 expression decreased significantly indicating that tramadol is harmful at the cellular level and can induce apoptotic changes in these tissues. Therefore, the toxic effects of tramadol should keep in mind, even though, the important role it plays as powerful pain management.