Relieving 5-fluorouracil-associated testicular toxicity in rats: Investigating the therapeutic potential of arbutin

Abstract

5-Fluorouracil (5-FU) is an effective chemotherapeutic agent used in the treatment of various malignancies, but is associated with side effects, including testicular toxicity. Arbutin (ARB) is an effective antioxidant that can be obtained from a variety of natural products, including wheat, broccoli and pear. The present study investigated the protective effect of ARB, a bioactive glycosylated hydroquinone, on 5-FU-induced reprotoxicity in male rats. The rats were administered a single dose of 5-FU (100 mg/kg) on day 1 and two different doses of ARB (5 and 10 mg/kg) for the following 3 days. The administration of 5-FU resulted in testicular damage, as evidenced by reduced serum testosterone levels and an increase in histopathological findings. The study also found that the administration of 5-FU to rats resulted in increased testicular lipid peroxidation, inflammation and apoptosis, and a decrease in antioxidant capacity. The adverse effects observed in rats administered 5-FU were mitigated by the induction of the nuclear factor erythroid 2-related factor 2 pathway following ARB administration. ARB may be considered a promising molecule to eliminate testicular toxicity after receiving 5-FU treatment. (c) 2025 SAAB. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.