The Serine Protease Inhibitor Camostat Mesilate Attenuates the Progression of Chronic Kidney Disease through its Antioxidant Effects
| Autor: | Yoshikazu Miyasato, Masataka Adachi, Yutaka Kakizoe, Jun Morinaga, Daisuke Kadowaki, Teruhiko Mizumoto, Yoshiki Sakai, Yuki Narita, Manabu Hayata, Miki Ueda, Masashi Mukoyama, Taku Miyoshi, Kenichiro Kitamura, Kohei Uchimura, Naoki Shiraishi |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Serine Proteinase Inhibitors Antioxidant Gabexate medicine.medical_treatment Blood Pressure Pharmacology Kidney Guanidines Antioxidants Rats Sprague-Dawley Fibrosis Camostat mesilate medicine Animals Renal Insufficiency Chronic Antihypertensive Agents Serine protease biology business.industry Esters Free Radical Scavengers Hydralazine Free radical scavenger medicine.disease Rats Sprague dawley Oxidative Stress Creatinine Immunology Disease Progression biology.protein Creatinine blood business Kidney disease |
| Zdroj: | Nephron. 129:223-232 |
| ISSN: | 2235-3186 1660-8151 |
| DOI: | 10.1159/000375308 |
| Popis: | Background/Aims: 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. Methods: 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. Results: 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 systolic blood pressure in HYD group. EPR study revealed that CM and its metabolites have potent hydroxyl radical scavenging activities in vitro. Conclusion: Our findings indicate that CM significantly ameliorates the progression of CKD partly through its antioxidant effect independently from its blood pressure-lowering effect. Our results suggest the possibility that CM could be a new therapeutic agent that could arrest the progression of CKD. |
| Databáze: | OpenAIRE |
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