en فارماکولوژی Pharmacology پژوهشي Original Research <strong>Background</strong>: The hepatotoxic effect of 5-fluorouracil (5-FU) can deprive cancer patients of its maximum therapeutic benefits. Selenium (Se) is a trace element with potential benefits in some animal models of diseases.<br> <strong>Objectives</strong>: This study assessed the ability of Se to nullify the hepatotoxic effect of 5-FU in albino rats.&nbsp;<br> <strong>Methods</strong>: In this study, 40 adult male albino rats were grouped into A to D (each 5 rats). Rats in group A (control) were treated intraperitoneally (IP) with normal saline (0.2 mL) daily for 5 days. Rats in groups B1 to B3 were treated IP with Se (0.125, 0.25, and 0.50 mg/kg) daily for 5 days, respectively. Rats in group C were treated IP with 5-FU (20 mg/kg) daily for 5 days. Rats in groups D1to D3 were treated IP with Se with 0.125, 0.25, and 0.50 mg/kg before treatment with 5-FU (20 mg/kg) daily for 5 days, respectively. After treatment, the rats were euthanized, and their blood samples were collected and evaluated for serum liver function. Liver samples were evaluated for biochemical and histological parameters.<br> <strong>Results</strong>: Liver and serum aminotransferases, gamma-glutamyl transferase, lactate dehydrogenase, alkaline phosphatase, total bilirubin, and conjugated bilirubin levels were significantly (P<0.001) high in 5-FU-treated rats in comparison to the control group. Liver glutathione peroxidase, superoxide dismutase (SOD), catalase, and glutathione levels were significantly (P<0.001) low whereas the malondialdehyde level was significantly (P<0.001) high in 5-FU-treated rats compared with the control group. Moreover, hepatocyte necrosis was observed in 5-FU-treated rats.&nbsp;<br> <strong>Conclusion</strong>: Nonetheless, 5-FU-induced hepatotoxicity was significantly nullified in rats supplemented with Se (0.125 mg/kg, P<0.05; 0.25 mg/kg, P<0.01, and 0.5 mg/kg, P<0.001) in a dose-dependent fashion in comparison to 5-FU-treated rats. Thus, Se may have a clinical benefit in 5-FU-induced hepatotoxicity 5-Fluorouracil, Liver chemotherapy, Toxicity, Selenium, Protection, Antioxidant 197 204 http://pbr.mazums.ac.ir/browse.php?a_code=A-10-744-2&slc_lang=en&sid=1 Elias Adikwu adikwuelias@gmail.com 10031947532846005844 10031947532846005844 No Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Amassama, Nigeria. Nelson Clemente Ebinyo adikwuelias@yahoo.com 10031947532846005845 10031947532846005845 Yes Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Amassama, Nigeria.