Curcumin mitigates aflatoxin B1-induced liver injury via regulating the NLRP3 inflammasome and Nrf2 signaling pathway

Food Chem Toxicol. 2022 Mar:161:112823. doi: 10.1016/j.fct.2022.112823. Epub 2022 Jan 19.

Abstract

Aflatoxins are produced as secondary metabolites by the toxigenic Aspergillus fungi. Among the aflatoxins, aflatoxin B1 (AFB1) is a common contaminant of global concern in human and animal food products. Prolonged exposure to AFB1 may provoke hepatocyte pyroptosis and oxidative stress, which leads to liver damage. Dietary polyphenols could protect the liver from a wide range of toxins. Curcumin, a polyphenolic substance derived from turmeric, is rich in pharmacological activity. The aim of this study was to systematically investigate the protective effects of curcumin against AFB1-induced liver injury in mice and to explore the possible molecular mechanisms. BALB/c mice received oral gavage of AFB1 (0.75 mg/kg) and curcumin (100 or 200 mg/kg) for 30 days. Our data demonstrated that curcumin attenuated AFB1-induced weight loss in mice and rescued liver injury by mitigating the alterations in pathology and liver function with AFB1 exposure. Curcumin reduced the accumulation of AFB1-DNA adducts in the liver and alleviated hepatotoxicity by inhibiting AFB1-induced oxidative stress and potentiating glutathione S-transferase (GST)-mediated phase II detoxification. In addition, curcumin significantly reduced the characteristic indices of AFB1-induced pyroptosis, such as the expression of mRNAs for genes related to NOD-like receptor protein 3 (NLRP3) inflammasome assembly and activation, the expression of key proteins (NLRP3, Caspase-1 and GSDMD). The release of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the serum detected by ELISA was also significantly decreased. Notably, administration of curcumin upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its related downstream antioxidant molecules (SOD, CAT, HO-1, NQO1) and phase II detoxification enzyme-related molecules (GST, GSH, GSS, GCLC, GCLM) in the presence of AFB1 exposure. To summarize, our results indicated that curcumin could modulate the NLRP3 inflammasome and Nrf2 signaling pathways to attenuate AFB1-induced liver pyroptotic damage and oxidative stress.

Keywords: Aflatoxin B1; Curcumin; NLRP3 inflammasome; Nrf2 signaling pathway; Oxidative stress; Pyroptosis.

MeSH terms

  • Aflatoxin B1 / toxicity*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Body Weight / drug effects
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Curcumin / pharmacology*
  • Gene Expression Regulation / drug effects
  • Hepatocytes / drug effects
  • Hepatocytes / ultrastructure
  • Inflammasomes / drug effects*
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Organ Size / drug effects
  • Poisons / toxicity

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Inflammasomes
  • NF-E2-Related Factor 2
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nfe2l2 protein, mouse
  • Nlrp3 protein, mouse
  • Poisons
  • Aflatoxin B1
  • Curcumin