Ephedra sinica mitigates hepatic oxidative stress and inflammation via suppressing the TLR4/MyD88/NF-κB pathway in fipronil-treated rats

Environ Sci Pollut Res Int. 2021 Nov;28(44):62943-62958. doi: 10.1007/s11356-021-15142-4. Epub 2021 Jul 3.

Abstract

Ephedra sinica (ES) is a promising medicinal plant with a wide range of pharmacological aspects, including antioxidant and anti-inflammatory properties. Fipronil (FN) is a popularly used systemic insecticide in agriculture and veterinary applications. FN exposure can result in a variety of negative health consequences. The study aimed to explore the prophylactic effects of Ephedra sinica extract (ESE) against hepatotoxicity in FN-treated rats by following the TLR4/ MyD88/ NF-κB pathway. ESE was tested for polyphenolic and antioxidant activity. Forty rats were separated into four groups and given orally by FN (10 mg/kg B.W.) and/or ESE (150 mg/kg B.W.). Blood and tissue samples were collected at the end of the experiment and prepared for pathophysiological, gene expression, and pathological analysis. ESE showed strong antioxidant activity, as well as reduced levels of hepatic MDA and oxidative stress markers (H2O2, NO). Hepatic SOD and CAT activities were increased even further. Furthermore, in FN-treated rats, ESE improved liver functions (ALT, AST, ALP, and LDH) and recovered the lipid profile (Cho, TriG, HDL, and LDL). Moreover, by inhibiting TLR4/ MyD88/ NF-κB induction, ESE alleviated hepatic pathological changes and decreased FN-induced elevations of TNF-α, IL-6, and IL-1β mRNA/protein levels. These findings suggested that ESE mitigated FN-induced hepatotoxicity via combating oxidative stress and relieving inflammation.

Keywords: Anti-inflammation,; Ephedra sinica,; Liver injury,; Rats,; TLR4/MyD88/NF-κB.

MeSH terms

  • Animals
  • Ephedra sinica* / metabolism
  • Hydrogen Peroxide / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Liver / metabolism
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B* / metabolism
  • Oxidative Stress
  • Pyrazoles
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Toll-Like Receptor 4 / metabolism

Substances

  • Myd88 protein, rat
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Pyrazoles
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Hydrogen Peroxide
  • fipronil