ABSTRACT
Objective @# To investigate the effect of high concentration of Caerulomycin A (Cae A) on HK2 in renal tubular epithelial cells and to explore the role of cytoplasmic nucleotide⁃binding oligomerization domain⁃like receptor protein 3 (NLRP3) in this process.@*Methods @# The effect of different concentrations of Cae A on the viability of HK2 cells was determined by MTT; the expression of kidney injury molecule (KIM⁃1) and NLRP3 was detected by real⁃time quantitative PCR , Western blot and immunofluorescence , while the effect of Cae A on the mRNA expression of IL⁃1β , IL⁃18 , IL⁃33 , MCP⁃1 , TNF⁃α was also measured by real⁃time quantitative PCR. HK2 cells were divided into control group , high concentration of Cae A group and high concentration of Cae A plus NLRP3 inhibitor CY⁃09 group , and the expression of KIM⁃1 and NLRP3 protein was detected by Western blot.@*Results @#The results of MTT showed that high concentration of Cae A could inhibit HK2 cell viability. Real⁃time quantitative PCR , Western blot and immunofluorescence assays showed that high concentration of Cae A upregulated the expression of KIM⁃1 and NLRP3 , as well as the mRNA levels of IL⁃1β , IL⁃18 , IL⁃33 , MCP⁃1 , TNF⁃α , while CY⁃09 could down⁃regulate the expression of NLRP3 and KIM⁃1.@*Conclusion @# High concentration of Cae A significantly inhibited the viability of HK2 cells and induced damage and inflammatory response to HK2 with some nephrotoxicity that might be achieved via NLRP3 pathway.
ABSTRACT
Novel antineoplastic drugs have significantly prolonged the survival time of cancer patients. Meanwhile, nephrotoxicity of antineoplastic drugs and its adverse effects on the prognosis of cancer patients have received increasing attention. Conventional chemotherapy causes kidney injury mainly through direct renal toxicity, while new anti-tumor drugs can induce a number of kidney damage, including acute renal tubular injury, thrombotic microangiopathy, interstitial nephritis, and glomerular diseases through multiple mechanisms. Clinicians must be knowledgeable in the renal toxicity of antineoplastic drugs to minimize the nephrotoxicity of the drugs and diagnose early, especially in patients with underlying kidney disease. This article focuses on the risk factors, clinical and histological patterns, pathogenesis, prevention and treatment of renal injury associated with the antineoplastic drugs, especially novel targeted antineoplastic drugs.