Year: 2024
Type: article
Abstract: Although cisplatin is a useful antitumor drug, its nephrotoxicity is a critical limiting factor for this chemotherapy. The present study examined if mast cell-derived chymase might contribute to this pathology, through analysis of the pattern of chymase expression, as well as the effects of chymase inhibition, in a mouse cisplatin-induced nephrotoxicity model. We found that mast cells positive for the chymase, murine mast cell protease-4 (MMCP-4), and MMCP-4 mRNA expression in kidney tissues increased largely during the acute phase after cisplatin injection. Increase in serum creatinine and blood urea nitrogen, as well as histopathological changes such as renal tubular enlargement, were also observed in cisplatin-injected mice. Only half of the cisplatin-injected mice survived during the 6-day observation period. mRNA expression of reactive oxygen species-related factors, as well as inflammationrelated factors, such as NOX2 and TNF-α, were all significantly increased in the acute phase after cisplatin injection. On the other hand, reduction in mast cell-derived chymase expression, along with improvement in renal function, histopathological changes, and survival rates, were observed in cisplatin-induced nephrotoxic mice treated with a chymase-specific inhibitor, suggesting that chymase plays an important role in cisplatin-induced nephrotoxicity in mice.
Institution: Osaka Medical and Pharmaceutical University
Language: English
Subfield: Toxicology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7144899791