Ameliorate effect of pyrroloquinoline quinone against cyclophosphamide-induced nephrotoxicity by activating the Nrf2 pathway and inhibiting the NLRP3 pathway

• DOI: 10.1016/j.lfs.2020.117901
• Publication Date: 2020-06-03T15:17:46Z
• Authors: Xinhui Lin; Fei Yang; Ju Huang; Su Jiang; Yunping Tang; Jianrong Li
• Keywords: Inflammation; Male; 0301 basic medicine; Mice, Inbred ICR; NF-E2-Related Factor 2; Body Weight; PQQ Cofactor; Organ Size; Kidney; Models, Biological; Antioxidants; Blood Urea Nitrogen; 3. Good health; 03 medical and health sciences; Creatinine; Malondialdehyde; NLR Family, Pyrin Domain-Containing 3 Protein; Animals; Cytokines; Kidney Diseases; Inflammation Mediators; Cyclophosphamide; Signal Transduction

Cyclophosphamide (CTX) is an effective anti-tumor and immunosuppressive agent, but it induces nephrotoxicity in clinical applications. The present study aimed to evaluate the protective effect of pyrroloquinoline quinone (PQQ) on CTX-induced nephrotoxicity.We injected male ICR mice with CTX (80 mg/kg/day), and determined nephrotoxicity indices, MDA and antioxidant defenses, inflammatory cytokines, and the levels of main proteins in the Nrf2-HO-1 and NLRP3 signaling pathways.PQQ has significantly decreased the serum levels of creatinine and urea compared to Model group. When treated with PQQ, MDA, IL-1β, IL-6, and TNF-α levels have decreased, and SOD, GSH-Px, and CAT activity have increased in the kidney tissues of CTX-induced mice. PQQ activated the Nrf2-mediated signaling pathway, as indicated by the increased expression of Nrf2, HO-1, GCLM, and NQO1. Moreover, PQQ inhibited the NLRP3 inflammatory pathway, as indicated by the reduced expression of NLRP3, ASC, and Caspase-1.Our results suggest that PQQ protects against CTX-induced nephrotoxicity, probably by activating the Nrf2-mediated antioxidant pathway and inhibiting the NLRP3 inflammatory pathway.