Rosmarinic Acid Prevents Cisplatin-Induced Liver and Kidney Injury by Inhibiting Inflammatory Responses and Enhancing Total Antioxidant Capacity, Thereby Activating the Nrf2 Signaling Pathway

Molecules. 2022 Nov 13;27(22):7815. doi: 10.3390/molecules27227815.

Abstract

Drug-induced liver and kidney damage is an emergent clinical issue that should be addressed. Rosmarinic acid (RA) has obvious anti-inflammatory and antioxidant effects, so we evaluated the anti-inflammatory and antioxidant effects of RA pretreatment on serum and liver and kidney tissues of cisplatin (CP)-treated mice and explored the possible mechanisms. The results showed that RA pretreatment effectively downregulated the serum, liver, and kidney levels of ALT, AST, BUN, and CRE and the inflammatory factors IL-1β, IL-6, and TNF-α, and simultaneously enhanced the total antioxidant capacity of the liver and kidney. RA pretreatment significantly reduced the levels of MPO, MDA, and NO in liver and kidney tissue, inhibited the mRNA expression of IL-1β, IL-6, and TNF-α in liver and kidney tissue, activated the Nrf2 signaling pathway, and upregulated the mRNA expression of downstream target genes. Our findings show that RA could effectively prevent and alleviate acute liver and kidney injury caused by CP.

Keywords: Nrf2; acute liver and kidney injury; cisplatin; inflammation; oxidative stress; rosmarinic acid.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants* / metabolism
  • Cisplatin / pharmacology
  • Interleukin-6 / metabolism
  • Kidney
  • Liver
  • Mice
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • NF-kappa B / metabolism
  • RNA, Messenger / metabolism
  • Rosmarinic Acid
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • NF-E2-Related Factor 2
  • Antioxidants
  • Cisplatin
  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • NF-kappa B
  • Anti-Inflammatory Agents
  • RNA, Messenger