Lentinan alleviates cadmium-induced kidney injury by reducing cadmium accumulation via promoting cadmium excretion and metallothionein synthesis and regulating silencing information regulator1/nuclear factor erythroid 2–related factor 2/nuclear factor kappa-B signaling pathway

Abstract

Cadmium (Cd) is a widely distributed environmental heavy metal pollutant. It is extremely toxic to the kidney. This study investigated the potential mechanisms of action of lentinan (LNT), a fungal polysaccharide, on protecting against Cd-induced kidney injury in mice. Male Kunming mice were administered with CdCl₂ (2.5 mg/kg/b.w.) by intragastric gavage and LNT in drinking water (1 mg/mL) for 10 weeks. Histological examination revealed that LNT reduced the glomerular atrophy, lymphocyte infiltration, tubular congestion, and collagen accumulation caused by Cd exposure. However, oral administration of LNT decreased Cd levels in kidney by promoting the excretion of Cd in feces and increasing the production of metallothionein (MT) in the kidney. In addition, LNT treatment alleviated Cd-induced kidney excessive mitophagy by upregulating silencing information regulator1 (SIRT1) and prevented subsequent oxidative stress and inflammatory responses by upregulating nuclear factor erythroid 2–related factor 2 (Nrf2) and downregulating nuclear factor kappa-B (NF-κB) signaling pathways. Further, the protein expression levels of profibrotic factors, including Tgf-β1, alpha smooth muscle actin, and collagen type I alpha 1 chain, and the progression of fibrosis, were significantly reduced in the kidneys of mice treated with LNT. Collectively, our findings suggest that LNT can relieve the nephrotoxicity of Cd by decreasing its accumulation via promoting Cd excretion and MT synthesis and regulating the SIRT1/Nrf2/NF-κB signaling pathway.