Protective role of scutellarin to counteract arsenic prompted renal damage in rats via the regulation of Nrf2/Keap1 pathway

Int J Environ Health Res. 2026 May;36(5):1110-1120. doi: 10.1080/09603123.2025.2563062. Epub 2025 Sep 22.

Abstract

Arsenic intoxication is associated with acute renal failure which makes it a serious health concern worldwide. Scutellarin (SCU) is a flavonoid glucuronide that possesses a variety of therapeutic properties. Therefore, the current investigation was performed to ascertain the curative role of SCU to counteract arsenic instigated nephrotoxicity in rats. In this study, 48 albino rats were divided into four groups (n = 12/group): i) Control, ii) Arsenic (10 mgkg-1) group, iii) Arsenic + SCU (10 mgkg-1 +5 mgkg-1) treated group, and iv) SCU (5 mgkg-1) only treated group. Arsenic exposure downregulated the expressions of Nrf2, and its antioxidant genes, while increasing Keap-1 expressions. Arsenic administration reduced the activities of catalase (CAT), hemeoxygenase-1 (HO-1), superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione (GSH), and glutathione peroxidase (GPx), whereas escalated malondialdehyde (MDA) and reactive oxygen species (ROS) contents. Arsenic treatment significantly elevated the levels of urea, creatinine, KIM-1 and NGAL, while reducing the level of creatinine clearance. Additionally, arsenic exposure elevated the levels of inflammatory markers. Furthermore, it elevated Bax and caspase-3 expressions, while decreasing the expressions of Bcl-2. Arsenic treatment also led to considerable histopathological impairment. However, supplementation with SCU mitigated all the arsenic-induced damage in renal tissues of the rats due to its pharmacotherapeutic properties.

Keywords: Nephrotoxicity; antioxidant; arsenic; inflammation; scutellarin.

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / prevention & control
  • Animals
  • Antioxidants
  • Apigenin* / pharmacology
  • Arsenic* / toxicity
  • Glucuronates* / pharmacology
  • Kelch-Like ECH-Associated Protein 1* / genetics
  • Kelch-Like ECH-Associated Protein 1* / metabolism
  • Kidney / drug effects
  • Male
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Protective Agents* / pharmacology
  • Rats
  • Signal Transduction / drug effects

Substances

  • Apigenin
  • Glucuronates
  • NF-E2-Related Factor 2
  • scutellarin
  • Arsenic
  • Kelch-Like ECH-Associated Protein 1
  • KEAP1 protein, rat
  • Nfe2l2 protein, rat
  • Protective Agents
  • Antioxidants