Organ-specific effects of curcumin on favipiravir-induced oxidative stress: renal benefit and hepatic risk

Abstract

Fa vipiravir (FAV), an antiviral for influenza and COVID-19, can provoke hepatotoxicity and nephrotoxicity. Curcumin (CUR) has antioxidant and anti-inflammatory properties that may protect against FAV-induced toxicity. Despite the widespread clinical use of FAV, to our knowledge, no in vivo animal study has yet examined its organ-specific oxidative injury profile in parallel with the putative dual, organ-directed actions of CUR. This study evaluated whether curcumin can mitigate favipiravir-induced oxidative and apoptotic damage in rat liver and kidney. Male Wistar rats received FAV (100 mg/kg i.p.) and CUR (100 or 200 mg/kg p.o.) for 14 days. Serum biochemistry analysis was performed to assess levels of ALT, AST, IL-6, MDA, TNF-α, and GSH. Additionally, histopathological examination and TUNEL assay were conducted on kidney and liver tissues. ALT, AST, and cytokines did not differ among groups. MDA remained unchanged in the FAV-alone group but rose significantly with CUR co-treatment, signifying CUR-driven amplification of oxidative stress, especially in hepatic tissue. Histopathological analysis revealed liver and kidney damage from FAV, with CUR exacerbating liver damage but offering partial protection to kidney structures. The TUNEL assay showed reduced apoptosis in the kidneys with CUR, especially at higher doses. FAV causes sub-clinical liver and kidney injury that is not accompanied by lipid peroxidation or enzyme leakage at 14 days. CUR exerts dual actions-mitigating renal apoptosis yet amplifying hepatic lipid peroxidation-highlighting an organ-specific risk-benefit ratio that should be weighed before empirical antioxidant supplementation during FAV therapy.

Keywords: Curcumin; Favipiravir; Hepatotoxicity; Nephrotoxicity; Oxidative stress.