Ameliorative effect of Lactobacillus plantarum Lp2 against cyclophosphamide-induced liver injury in mice

Food Chem Toxicol. 2022 Nov:169:113433. doi: 10.1016/j.fct.2022.113433. Epub 2022 Sep 16.

Abstract

Cyclophosphamide (CTX) is a widely used anticancer drug that can cause liver injury, but there is no effective treatment available at present. The antioxidant properties of Lactobacillus plantarum Lp2 in vitro and its effect on CTX-induced liver injury in mice were investigated thoroughly. The order of antioxidant capacity of the fermentate of Lp2 was as followed: fermented supernatant > cell-free extract > intact cell. BALB/c mice were intraperitoneally injected with 80 mg/kg BW/d CTX for 3 days to build a liver injury model, then treated with Lp2 fermented supernatant (Lp2-s) and Lp2 culture broth (Lp2). After 10 days, the indicators of oxidative stress and liver injury were measured. Both Lp2-s and Lp2 restored the levels of T-SOD, CAT, GSH-Px, MDA, GSH, ALT, and AST. The western blotting results showed that Lp2-s and Lp2 ameliorated CTX-induced oxidative damage and hepatocyte apoptosis via inhibiting MAPKs pathway and strengthening Nrf2/HO-1/NQO1 antioxidant defense system, thus inhibiting the mitochondrial-mediated apoptosis pathway. Therefore, both Lp2-s and Lp2 had similar protective effects on CTX-induced liver injury.

Keywords: Cyclophosphamide; Lactobacillus plantarum Lp2; Liver injury; MAPKs signaling pathway; Oxidative stress.

MeSH terms

  • Animals
  • Antineoplastic Agents* / toxicity
  • Antioxidants* / pharmacology
  • Chemical and Drug Induced Liver Injury* / prevention & control
  • Chemical and Drug Induced Liver Injury* / therapy
  • Cyclophosphamide / toxicity
  • Lactobacillus plantarum* / metabolism
  • Liver / drug effects
  • Mice
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress* / drug effects
  • Superoxide Dismutase / metabolism

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Cyclophosphamide
  • NF-E2-Related Factor 2
  • Superoxide Dismutase