Investigation of the effects of crocin on inflammation, oxidative stress, apoptosis, NF-κB, TLR-4 and Nrf-2/HO-1 pathways in gentamicin-induced nephrotoxicity in rats

Environ Toxicol Pharmacol. 2024 Mar:106:104374. doi: 10.1016/j.etap.2024.104374. Epub 2024 Jan 19.

Abstract

The primary limitation of gentamicin (Gm) treatment is its potential to induce nephrotoxicity, which can restrict both its duration and efficacy. This study aims to investigate the protective effects of Crocin (Cr) against Gm-induced nephrotoxicity and its underlying mechanisms, including inflammation, apoptosis, TLR-4, Nrf-2/HO-1 pathways. 36 Sprague Dawley rats were divided into 6 groups for the study. Group I received only saline. Groups II and III were administered 25 and 50 mg/kg of crocin, respectively. Group IV was treated with 80 mg/kg of Gm. Groups V and VI received 25 and 50 mg/kg of crocin, respectively, in addition to Gm administration. Crocin demonstrated protective effects on kidney tissue. It down-regulated the genes NF-κB, COX-2, TLR-4, Bax, and Caspase-3, while up-regulating Bcl-2, Nrf-2, and HO-1. In conclusion, these findings hold promise for the prevention of Gm-induced nephrotoxicity through the modulation of the Nrf-2/HO-1 pathway.

Keywords: Apoptosis; Crocin; Gentamicin; Inflammation; Nephrotoxicity; Oxidative stress.

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / prevention & control
  • Animals
  • Apoptosis
  • Carotenoids* / pharmacology
  • Carotenoids* / therapeutic use
  • Gentamicins* / toxicity
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Kidney* / drug effects
  • NF-kappa B* / metabolism
  • Oxidative Stress
  • Rats
  • Rats, Sprague-Dawley
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism

Substances

  • Carotenoids
  • crocin
  • Gentamicins
  • NF-kappa B
  • Toll-Like Receptor 4