Effects of Thymoquinone on Tramadol Induced Toxicity in Epididymis of Adult Male Rabbits (Histological & Immunohistochemical Study)

Abstract

Millions of patients who administer or abuse tramadol to relieve chronic pain may suffer from infertility. Thymoquinone (TQ) is a major active component of nigella sativa oil, which has antioxidant and anti-inflammatory effects. The present work aimed to clarify effects of tramadol and TQ on epididymis of adult male rabbits. Forty adult male rabbits aged 3 months were used for one month & divided equally into 4 groups: Group 1 as a control group; group 2 was treated with tramadol 30 mg/kg orally/day, group 3 was treated with TQ 20 mg/kg orally/day and group 4 as a protected group that was treated with TQ 20 mg/kg & tramadol 30 mg/kg orally/day. The epididymis was processed for histological and immunohistochemical (IHC) study for detection of epididymal structure and caspase-3 as an indicator of epididymal apoptotic changes. Statistical analysis of apoptotic index, area% of collagen and caspase-3 immunoexpression was carried out. Group 2 showed epithelial thinning of epididymal wall, degeneration and vacuolation of epithelial cells with disturbance of stromal collagen fibers. Also, a significant increase of apoptotic index, area % of collagen and caspase-3 cytoplasmic immunoexpression in epididymal epithelium was noticed in group 2. While, Group 3 and 4 showed improvement of the histological and IHC changes described in group 2. It is concluded that tramadol intake exerted toxic effects on epididymal structure while, TQ minimized these effects. Therefore, intake of TQ with tramadol is advised to protect the epididymis from the hazardous effects of tramadol abuse.