Sinapic acid alleviates 5-fluorouracil-induced nephrotoxicity in rats via Nrf2/HO-1 signalling

Fluoropyrimidine 5-fluorouracil (5-FU) is a DNA analogue broadly used in chemotherapy, though treatment-associated nephrotoxicity limits its widespread clinical use. Sinapic acid (SA) has potent an-tioxidant, anti-inflammatory, and anti-apoptotic effects, we investigated its protective effects against 5-FU-induced nephrotoxicity in a rat model. We designated four treatment groups each Group I (control) received five intraperitoneal saline injections (once daily) from days 17 to 21; Group II received five in-traperitoneal injections of 5-FU (50 mg/kg/day) from days 17 to 21; Group III received an oral adminis-tration of SA (40 mg/kg) for 21 days and five intraperitoneal injections of 5-FU (50 mg/kg/day) from days 17 to 21; and Group IV received an oral administration of SA (40 mg/kg) for 21 days (n-six rats in each group). blood samples were collected on day 22 from each group. Animals were sacrificed and their kid-neys removed, and instantly frozen. 5-FU caused oxidative stress, inflammation, and activation of the apoptotic pathway by upregulating Bax and Caspase-3 and downregulating Bcl-2. However, SA exposure reduced serum toxicity indicators, boosted antioxidant defences, and reduced kidney apoptosis, which was confirmed by histopathological analysis. Therefore, prophylactic administration of SA could inhibit 5-FU-induced renal injuries in rats via suppression of renal inflammation and oxidative stress, primarily through regulation of NF-jB and proinflammatory cytokines, inhibition of renal apoptosis, and restora-tion of tubular epithelial antioxidant activities and cytoprotective defences.& COPY; 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study investigated the protective effects of sinapic acid (SA) against 5-fluorouracil (5-FU)-induced nephrotoxicity in a rat model. The results showed that SA can alleviate kidney damage caused by 5-FU by suppressing renal inflammation and oxidative stress, promoting antioxidant defense, and restoring cytoprotective mechanisms.