The Journal of Phytopharmacology 2026; 15(2):117-125 ;   DOI:10.31254/phyto.2026.15201

Research Article

Hepatorenal protective effect of rutin against sodium arsenite-induced oxido-inflammatory stress and Nrf-2/HO-1 pathway

Omorede Ikponmwosa-Eweka¹ , Ikenna Chukwuemeka Maduako²

Omorede Ikponmwosa-Eweka,Ikenna Chukwuemeka Maduako

1. Department of Medical Biochemistry, University of Benin, Nigeria
2. Chemoprevention and Toxicology Laboratory, Department of Medical Biochemistry, College of Medical Sciences, Benson Idahosa University, Benin City, Nigeria

*Author to whom correspondence should be addressed.

Received: 20th February, 2026 / Accepted: 3rd April, 2026 / Published : 17th April, 2026

Abstract

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Background: Arsenic is a persistent environmental contaminant that poses a serious public health risk due to its well-documented hepatotoxic and nephrotoxic properties. Exposure to sodium arsenite (NaAsO₂), a soluble inorganic arsenical compound, induces multi-organ injury through mechanisms involving oxidative stress, NF-κB-driven inflammation, and dysregulation of the Nrf2/HO-1 antioxidant pathway. Objective: This study investigated the hepatorenal protective effects of rutin (RUT) against NaAsO₂-induced hepatorenal toxicity in male rats, and sought to elucidate the underlying mechanisms with specific reference to oxidative stress, inflammatory signalling, and the Nrf2/HO-1 and NF-κB pathways. Materials and Methods: Forty male Wistar rats were randomly allocated into five groups (n = 8 per group) and treated orally for 14 days as follows: Group I, vehicle control; Group II, RUT alone (50 mg/kg); Group III, NaAsO₂ alone (10 mg/kg); Group IV, NaAsO₂ (10 mg/kg) + RUT (25 mg/kg); and Group V, NaAsO₂ (10 mg/kg) + RUT (50 mg/kg). Hepatotoxicity and nephrotoxicity were evaluated using serum biochemical markers (ALP, ALT, urea, and creatinine), histopathological examination of liver and kidney tissues, and biochemical assessment of oxidative stress indices (MDA, RONS, NO, and GSH) and inflammatory signalling proteins (NF-κB, RANTES, and Nrf2/HO-1). Results: NaAsO₂ exposure significantly impaired hepatic and renal redox homeostasis, markedly elevating lipid peroxidation (MDA), reactive oxygen and nitrogen species (RONS), nitric oxide (NO), NF-κB, and RANTES, while depleting GSH content and suppressing the Nrf2/HO-1 pathway. These biochemical perturbations were accompanied by significant histopathological alterations in both liver and kidney tissues. Co-administration of RUT dose-dependently and significantly ameliorated all these changes, suppressing NF-κB activation and its downstream pro-inflammatory targets, restoring GSH levels, and upregulating Nrf2/HO-1 expression. Histological examination confirmed that RUT markedly attenuated NaAsO₂-induced structural disruption in hepatic and renal tissues. Conclusion: Rutin confers potent hepatorenal protection against NaAsO₂-induced toxicity through coordinated free-radical scavenging, NF-κB-mediated suppression of inflammation, and activation of the Nrf2/HO-1 antioxidant pathway. These findings suggest that RUT represents a promising therapeutic candidate for mitigating arsenic-induced hepatorenal organ damage.

Keywords

Rutin, Sodium Arsenite, NF-?B, Nrf2/HO-1 Pathway, Oxidative Stress, Hepatorenal Injury.

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