Saikosaponin a attenuates lead-induced kidney injury through activating Nrf2 signaling pathway

Comp Biochem Physiol C Toxicol Pharmacol. 2021 Apr:242:108945. doi: 10.1016/j.cbpc.2020.108945. Epub 2020 Dec 3.

Abstract

Saikosaponin a (SSa), a triterpene saponin extracted from Bupleurumfalcatum L., has been reported to have anti-inflammatory activity. In the present study, we investigated the effects of SSa on lead-induced kidney injury in common carp. Kidney histological changes were detected by H&E staining. The levels of TNF-α, IL-1β, MPO, MDA, GSH, and SOD activity were also measured. Furthermore, the NF-κB and Nrf2 signaling pathways were tested by western blot analysis. The results showed that lead-induced kidney histological change was attenuated by SSa. Lead-induced TNF-α, IL-1β, MPO, and MDA production were also suppressed by SSa. Meanwhile, lead could decrease GSH level and SOD activity and the decreases were inhibited by SSa. Furthermore, we found SSa significantly inhibited lead-induced NF-κB translocation. In addition, the expression of Nrf2 and HO-1 were increased by the treatment of SSa and Keap1 expression was decreased by SSa. In conclusion, this study indicated that SSa inhibited lead-induced kidney injury in carp through suppressing inflammatory and oxidative responses, and the mechanism may be involved in the inhibition of NF-κB and activation of Nrf2 signaling pathway.

Keywords: Carp; Lead; Nrf2; Saikosaponin a.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / drug therapy
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / veterinary*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Carps*
  • Fish Diseases / chemically induced
  • Fish Diseases / drug therapy*
  • Fish Diseases / metabolism
  • Fish Proteins / metabolism*
  • Lead / toxicity*
  • Lead Poisoning / drug therapy
  • Lead Poisoning / metabolism
  • Lead Poisoning / veterinary*
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism*
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology
  • Oxidative Stress*
  • Random Allocation
  • Saponins / pharmacology*
  • Signal Transduction / drug effects*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Fish Proteins
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Saponins
  • Lead
  • Oleanolic Acid
  • saikosaponin D