Is MCC950, an NLRP3 inflammasome inhibitor, a renopreventive: A chronic renal failure adenine model in rats

Abstract

Abstract Background: Chronic renal failure (CRF) is characterized by a great loss in renal function ending with reduced sodium filtration and suppression of tubular reabsorption that eventually leads to volume expansion. The contradictory information on the MCC950 renal effects brought this study to evaluate the possible renopreventive effects of NLRP3 inflammasome inhibitor MCC950 in adenine-induced CRF in rats. Methods: Adding 0.75% of adenine powder to a rat’s ration daily for 4 weeks is measured as a broad approval to be a model of evaluation of kidney damage as it is similar to most of the kidney tubular alterations seen in chronic kidney-diseased patients. Blood pressure was monitored at baseline and weekly during the test. Also, oxidative stress factors, urine sample analysis, histopathological changes, and immunohistochemical alterations of caspase-3 and interleukin-1 beta (IL-1β) levels in renal tissues were done. Results: Results showed that the NLRP3 inflammasome inhibitor MCC950 had a renopreventive effect that was established by a decrease in blood pressure measurements, and improvement of urinary, serum, and renal tissue markers as revealing organ damage. This was also revealed by the reduction of tubular expression of neutrophil gelatinase-associated lipocalin (NGAL). Immunohistochemical studies revealed that the worsened renal cellular changes indicated by raised expression of caspase-3 and IL-1β were prominently improved by NLRP3 inflammasome inhibitor MCC950 administration. Conclusion: The NLRP3 inflammasome inhibitor MCC950 administration in the CRF rat model had renopreventive effects which may be a potential therapeutic approach to prevent the progression of CRF.