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AuthorTan, Yong Chia
AuthorAbdul Sattar, Munavvar
AuthorAhmeda, Ahmad F
AuthorAbdul Karim Khan, Nurzalina
AuthorMurugaiyah, Vikneswaran
AuthorAhmad, Ashfaq
AuthorHassan, Zurina
AuthorKaur, Gurjeet
AuthorAbdulla, Mohammed Hadi
AuthorJohns, Edward James
Available date2020-04-26T06:21:19Z
Publication Date2020
Publication NamePLoS ONEen_US
Identifierhttp://dx.doi.org/10.1371/journal.pone.0231472
CitationTan YC, Abdul Sattar M, Ahmeda AF, Abdul Karim Khan N, Murugaiyah V, Ahmad A, et al. (2020) Apocynin and catalase prevent hypertension and kidney injury in Cyclosporine A-induced nephrotoxicity in rats. PLoS ONE 15(4): e0231472. https://doi.org/10.1371/journal.pone.0231472
ISSN1932-6203
URIhttp://hdl.handle.net/10576/14495
AbstractOxidative stress is involved in the pathogenesis of a number of diseases including hypertension and renal failure. There is enhanced expression of nicotinamide adenine dinucleotide (NADPH oxidase) and therefore production of hydrogen peroxide (H2O2) during renal disease progression. This study investigated the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on Cyclosporine A (CsA) nephrotoxicity in Wistar-Kyoto rats. Rats received CsA (25mg/kg/day via gavage) and were assigned to vehicle, apocynin (2.5mmol/L p.o.), catalase (10,000U/kg/day i.p.) or apocynin plus catalase for 14 days. Renal functional and hemodynamic parameters were measured every week, and kidneys were harvested at the end of the study for histological and NADPH oxidase 4 (NOX4) assessment. Oxidative stress markers and blood urea nitrogen (BUN) were measured. CsA rats had higher plasma malondialdehyde (by 340%) and BUN (by 125%), but lower superoxide dismutase and total antioxidant capacity (by 40%, all P<0.05) compared to control. CsA increased blood pressure (by 46mmHg) and decreased creatinine clearance (by 49%, all P<0.05). Treatment of CsA rats with apocynin, catalase, and their combination decreased blood pressure to near control values (all P<0.05). NOX4 mRNA activity was higher in the renal tissue of CsA rats by approximately 63% (P<0.05) compared to controls but was reduced in apocynin (by 64%), catalase (by 33%) and combined treatment with apocynin and catalase (by 84%) compared to untreated CsA rats. Treatment of CsA rats with apocynin, catalase, and their combination prevented hypertension and restored renal functional parameters and tissue Nox4 expression in this model. NADPH inhibition and H2O2 scavenging is an important therapeutic strategy during CsA nephrotoxicity and hypertension.
Languageen
PublisherPublic Library of Science
SubjectApocynin
Subjectcatalase
SubjectCyclosporine A-induced nephrotoxicity
SubjectNADPH oxidase
SubjectOxidative Stress
TitleApocynin and catalase prevent hypertension and kidney injury in Cyclosporine A-induced nephrotoxicity in rats.
TypeArticle
Issue Number4
Volume Number15


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