Pyrroloquinoline quinone ameliorates liver injury in mice induced by cyclophosphamide

Environ Sci Pollut Res Int. 2022 Apr;29(20):30383-30393. doi: 10.1007/s11356-021-17990-6. Epub 2022 Jan 8.

Abstract

The current study aimed to investigate the potential ameliorative effects of pyrroloquinoline quinone (PQQ) on cyclophosphamide (CTX)-induced liver injury in mice. The liver injury model was established by injecting mice with CTX (80 mg/kg/day). Liver function indices, antioxidant enzyme activities, and inflammatory cytokines were evaluated. In addition, protein expression levels of the nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) pathways in the liver tissues were determined using western blot. The results indicated that PQQ decreased the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the malondialdehyde (MDA), interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) levels in the liver tissues. Moreover, PQQ enhanced the activities of oxidative stress markers to alleviate CTX induced oxidative stress. Furthermore, the expression levels of heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone oxidoreductase 1 (NQO1) were significantly increased, and the expression levels of NF-κB p50, NF-κB p65, and inhibitor of NF-κB kinase alpha (IKKα) were significantly decreased after PQQ administration, suggesting that PQQ alleviated CTX-induced liver injury via activating the Nrf2-mediated antioxidant response pathway, and inhibiting the NF-κB-mediated inflammation pathway. Therefore, PQQ can be potentially used as a dietary supplement or functional foods for alleviating the CTX-induced liver injury.

Keywords: Cyclophosphamide; Liver injury; NF-κB pathway; Nrf2 pathway; Pyrroloquinoline quinone.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Chemical and Drug Induced Liver Injury, Chronic* / metabolism
  • Chemical and Drug Induced Liver Injury, Chronic* / pathology
  • Cyclophosphamide / metabolism
  • Cyclophosphamide / toxicity
  • Liver
  • Mice
  • NF-E2-Related Factor 2* / metabolism
  • NF-kappa B / metabolism
  • Oxidative Stress
  • PQQ Cofactor / metabolism
  • PQQ Cofactor / pharmacology
  • Signal Transduction

Substances

  • Antioxidants
  • NF-E2-Related Factor 2
  • NF-kappa B
  • PQQ Cofactor
  • Cyclophosphamide