The molecular and biochemical insight view of lycopene in ameliorating tramadol-induced liver toxicity in a rat model: implication of oxidative stress, apoptosis, and MAPK signaling pathways

Abstract

The influence of tramadol (TD) on hepatic tissue and the potential efficiency of lycopene to mitigate TD-induced hepatotoxic impacts were determined. Forty male albino rats were allocated into four groups: group I, untreated (placebo); group II, injected with TD (15 mg kg^-1) intraperitoneally (i.p.); group III, gastrogavaged with lycopene (10 mg kg^-1) per os (p.o.); and group IV received TD with lycopene with the same mentioned doses for 15 days. The results demonstrated that TD induced augmentation in tissue lipid peroxidation biomarker and disturbance in the antioxidant homeostasis and elevated the activity of serum liver injury biomarkers and decreased serum protein, globulin, and albumin. Hepatic glutathione S-transferase (GST), superoxide dismutase (SOD), thioredoxin-1 (Txn-1), and catalase (CAT) activities and gene expression were decreased and glutathione content was reduced in the TD-challenged rats, and these effects were alleviated by lycopene. Furthermore, TD induced apoptosis in liver tissues as shown by DNA fragmentation and upregulation of proapoptotic Bax and Casp-3 while lycopene upregulated the antiapoptotic Bcl-2. The results of Western blot showed that lycopene initiated low expression of mitogen activated protein kinase pathway (MAPK) protein expression in liver tissues of TD-challenged rats. In addition, lycopene reduced fatty degeneration and necrosis of the liver in TD-challenged group. Our data demonstrate that lycopene appears to be highly efficient in mitigating the hepatotoxic impacts of TD by preventing lipid peroxidation and initiating modifications in the expression and activity of antioxidant pathways. Surprisingly, lycopene fortified liver tissue by inhibiting DNA fragmentation and apoptosis signaling induced by TD. MAPK activation may be dependent from ROS generation; due to lycopene which possessed antioxidant potential did have a substantial effect on MAPK activity.

Keywords: Apoptosis; Gene expression; Hepatotoxicity; Lycopene; Oxidative stress; Tramadol.