The College of Pharmacy discussed the MSc thesis entitled “Possible Protective Effects of Two Consecutive Doses of Butein against 5-Fluorouracil-induced Hepatotoxicity in Rats” by the student Ruaa Adnan Mohamed and the supervisor, Professor Dr. Nada Naji AL-shawi, at the Pharmacology and Toxicology Department. The study aimed to evaluate the possible protective effect of two doses of Butein against 5-fluorouracil (5-FU)-induced hepatotoxicity in rats. The study included 28 male rats that were allocated into four groups of seven and treated as follows: Group I rats received 1 mL/kg corn oil orally for 14 consecutive days, Group II rats received 1 mL/kg corn oil orally for 14 consecutive days, and a single intraperitoneal injection of 150 mg/kg 5-FU on the 14th day of the experiment, Group III rats received 50 mg/kg Butein orally for 14 consecutive days, and a single intraperitoneal injection of 150 mg/kg 5-FU on the 14th day of the experiment, Group IV rats received 100 mg/kg Butein orally for 14 consecutive days, and a single intraperitoneal injection of 150 mg/kg 5-FU on the 14th day of the experiment. After 24 hours from final administration, the experimental rats were anesthetized, after which blood and liver tissue samples were obtained for biochemical, molecular, and histopathological analyses.
The results showed that rats pretreated with Butein at a dose of 50 or 100 mg/kg had an improvement in liver tissues, as well as a reduction in the levels of the liver enzymes ALT and AST in serum, compared to the 5-FU group. In addition, pretreating rats with either dose of Butein mitigated 5-FU-induced oxidative stress by elevating glutathione (GSH) levels, reducing malondialdehyde (MDA) levels, and upregulating the gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in liver tissues. Furthermore, pretreatment with either dose of Butein attenuated 5-FU-mediated inflammation by elevating interleukin-10 (IL-10) levels and reducing interleukin-6 (IL-6) and nuclear factor-kappa B (NF-κB) levels in serum, as well as downregulating the gene expression of tumor necrosis factor-alpha (TNF-α) in liver tissues. Also, pretreating rats with either dose of Butein alleviated 5-FU-induced apoptosis by downregulating the gene expression of caspase-3 in liver tissues.
The study recommended that further preclinical and clinical evaluation of Butein should be conducted to establish its safety and confirm its role as a hepatoprotective adjunct in cancer chemotherapy.
