The College of Pharmacy discussed the MSc thesis entitled “The Protective Effect of Nobiletin and Vitamin E Against 5-Fluorouracil Induced Hepatotoxicity in Male Rats: A Comparison Study” by the student Safa Ahmed Yahya and the supervisor, Professor Dr. Nada Naji Al-Shawi at the Pharmacology and Toxicology Department.The study aimed to investigate the effects of nobiletin on 5-fluorouracil-induced hepatotoxicity in male rats by measuring selected markers of inflammation, apoptosis, and oxidative stress, and to compare its effects with those of vitamin E.The study involved using male rats, inducing hepatotoxicity via intraperitoneal injection of 5-fluorouracil, and protecting the liver of a specific group of rats with nobiletin. The liver tissue was then utilized for analyses of various biochemical, Western blot, quantitative reverse transcriptase polymerase chain reaction, and histopathological architectures examination. The results were compared with another group that was treated with vitamin E as a preventive substance against the induced hepatotoxicity. All parameters were analyzed using GraphPad Prism 8, and the various groups were compared using one-way ANOVA. The results showed that the administration of nobiletin before 5-fluorouracil significantly improved liver function tests, including alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. Nobiletin inhibited the 5-fluorouracil-induced hepatic oxidative stress, including malondialdehyde levels, and increased the reduced form of glutathione. Furthermore, nobiletin inhibited the 5-florouracil-mediated induction of inflammatory markers such as interleukin-6, while increasing the anti-inflammatory marker interleukin-10. Additionally, nobiletin inhibited the effect of 5-fluorouracil in the induction of the apoptotic marker caspase-3. Nobiletin also increased the gene expression of heme oxygenase-1 and the activity of NADPH quinone dehydrogenase-1, compared to the group of rats that received only 5-fluorouracil injection. Histopathological analysis showed reduced congestion and inflammatory infiltration in the livers of rats treated with nobiletin before 5-fluorouracil administration. The study recommended using nobiletin as a treatment after the administration of 5-fluorouracil to explore its therapeutic potential in cases of hepatotoxicity induced by 5-fluorouracil. It also suggested investigating its protective effects on other organs in larger-scale studies.
