The serine protease inhibitor camostat mesilate attenuates the progression of chronic kidney disease through its antioxidant effects

Nephron
Miki UedaKenichiro Kitamura

Abstract

We have so far demonstrated the renoprotective effect of camostat mesilate (CM) in 5/6 nephrectomized rats at least partly through its antioxidant effect. However, precise mechanisms were not fully clarified. Therefore, we now examined the renoprotective and antioxidant mechanisms of CM by using the adenine-induced chronic kidney disease (CKD) rat model. In protocol 1, we analyzed the effect of CM on CKD. Rats were fed on a 0.75% adenine diet for 3 weeks to induce CKD followed by the experimental period with vehicle, CM, or hydralazine (HYD) treatment for 5 weeks. In protocol 2, we examined the safety of CM and HYD on the normal rats. In addition, we explored free radical scavenging activities of CM and its metabolites in vitro using electron paramagnetic resonance (EPR) spectroscopy. CM, but not HYD, significantly reduced the serum creatinine levels, although both treatments showed similar reduction in the blood pressure. CM decreased mRNA expression and protein levels of fibrotic markers, the severity of renal fibrosis, the accumulation of oxidative stress, and the expression of NADPH oxidase components in the kidney. In the protocol 2, there were no statistically significant differences in general parameters except for the s...Continue Reading

Citations

Oct 25, 2016·Journal of Pharmacological Sciences·Yutaka KakizoeKenichiro Kitamura
May 28, 2016·Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine·Kenichiro Kitamura
Mar 11, 2021·Journal of Pharmaceutical Investigation·Doaa A GhareebMaha A El-Demellawy

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