Atorvastatin improves renal organic anion transporter 3 and renal function in gentamicin-induced nephrotoxicity in rats

© 2016 The Authors. New Findings: What is the central question of this study? This study was designed to determine the renoprotective effects of atorvastatin treatment in an experimental model of gentamicin-induced nephrotoxicity through modulating the Nrf2 pathway by decreasing the oxidative stress...

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Main Authors: Krit Jaikumkao, Anchalee Pongchaidecha, Nipon Chattipakorn, Varanuj Chatsudthipong, Sasivimon Promsan, Phatchawan Arjinajarn, Anusorn Lungkaphin
Format: Journal
Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/55198
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spelling th-cmuir.6653943832-551982018-09-05T02:53:00Z Atorvastatin improves renal organic anion transporter 3 and renal function in gentamicin-induced nephrotoxicity in rats Krit Jaikumkao Anchalee Pongchaidecha Nipon Chattipakorn Varanuj Chatsudthipong Sasivimon Promsan Phatchawan Arjinajarn Anusorn Lungkaphin Biochemistry, Genetics and Molecular Biology © 2016 The Authors. New Findings: What is the central question of this study? This study was designed to determine the renoprotective effects of atorvastatin treatment in an experimental model of gentamicin-induced nephrotoxicity through modulating the Nrf2 pathway by decreasing the oxidative stress. What is the main finding and its importance? Atorvastatin exerts a nephroprotective effect by attenuating oxidative stress, protecting renal function and renal organic anion transporter 3 function from the effects of gentamicin. Atorvastatin might protect the tissues via its antioxidant property and by modulating the antioxidant enzymes through the Nrf2 signalling pathway, which may be the underlying mechanisms of these protective effects. Recent evidence demonstrates that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, exert not only lipid-lowering effects but also antioxidant, anti-inflammatory and anti-apoptotic effects. Nephrotoxicity, a serious side-effect of gentamicin, is related to an increase in reactive oxygen species in the kidney. This study was designed to determine the renoprotective effects of atorvastatin treatment in an experimental model of gentamicin-induced nephrotoxicity. Male Sprague-Dawley rats were used. Nephrotocixity was induced by i.p. injection of gentamicin, 100 mg kg-1day-1, for 15 days. Atorvastatin, 10 mg kg-1day-1, was administered by gavage 30 min before gentamicin injection (pretreatment) for 15 days or only on days 10-15 (post-treatment). Renal function and renal organic anion transporter 3 (Oat3) function and expression were examined. Gentamicin-treated rats demonstrated impaired renal function by attenuation of creatinine clearance and increased oxidative stress. Gentamicin treatment also decreased renal Oat3 function and expression as shown by decreased [3H]estrone sulfate uptake into renal cortical slices and decreased expression. The protein expressions of protein kinase C, Nrf2, NAD(P)H:quinone oxidoreductase 1, haeme oxygenase 1 and glutamate-cysteine ligase were markedly increased in gentamicin-treated rats, indicating the increase in oxidative stress. Administration of atorvastatin improved renal function and alleviated oxidative stress, and atorvastatin pretreatment had a greater ability to decrease oxidative stress than atorvastatin post-treatment. These effects helped to preserve renal function and Oat3 function and expression. These results indicate that atorvastatin has a renoprotective effect against gentamicin-induced nephrotoxicity by decreasing overoxidation in the kidney, and might be used in conjunction with gentamicin to protect against renal damage. 2018-09-05T02:53:00Z 2018-09-05T02:53:00Z 2016-06-01 Journal 1469445X 09580670 2-s2.0-84965166758 10.1113/EP085571 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84965166758&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/55198
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Biochemistry, Genetics and Molecular Biology
spellingShingle Biochemistry, Genetics and Molecular Biology
Krit Jaikumkao
Anchalee Pongchaidecha
Nipon Chattipakorn
Varanuj Chatsudthipong
Sasivimon Promsan
Phatchawan Arjinajarn
Anusorn Lungkaphin
Atorvastatin improves renal organic anion transporter 3 and renal function in gentamicin-induced nephrotoxicity in rats
description © 2016 The Authors. New Findings: What is the central question of this study? This study was designed to determine the renoprotective effects of atorvastatin treatment in an experimental model of gentamicin-induced nephrotoxicity through modulating the Nrf2 pathway by decreasing the oxidative stress. What is the main finding and its importance? Atorvastatin exerts a nephroprotective effect by attenuating oxidative stress, protecting renal function and renal organic anion transporter 3 function from the effects of gentamicin. Atorvastatin might protect the tissues via its antioxidant property and by modulating the antioxidant enzymes through the Nrf2 signalling pathway, which may be the underlying mechanisms of these protective effects. Recent evidence demonstrates that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, exert not only lipid-lowering effects but also antioxidant, anti-inflammatory and anti-apoptotic effects. Nephrotoxicity, a serious side-effect of gentamicin, is related to an increase in reactive oxygen species in the kidney. This study was designed to determine the renoprotective effects of atorvastatin treatment in an experimental model of gentamicin-induced nephrotoxicity. Male Sprague-Dawley rats were used. Nephrotocixity was induced by i.p. injection of gentamicin, 100 mg kg-1day-1, for 15 days. Atorvastatin, 10 mg kg-1day-1, was administered by gavage 30 min before gentamicin injection (pretreatment) for 15 days or only on days 10-15 (post-treatment). Renal function and renal organic anion transporter 3 (Oat3) function and expression were examined. Gentamicin-treated rats demonstrated impaired renal function by attenuation of creatinine clearance and increased oxidative stress. Gentamicin treatment also decreased renal Oat3 function and expression as shown by decreased [3H]estrone sulfate uptake into renal cortical slices and decreased expression. The protein expressions of protein kinase C, Nrf2, NAD(P)H:quinone oxidoreductase 1, haeme oxygenase 1 and glutamate-cysteine ligase were markedly increased in gentamicin-treated rats, indicating the increase in oxidative stress. Administration of atorvastatin improved renal function and alleviated oxidative stress, and atorvastatin pretreatment had a greater ability to decrease oxidative stress than atorvastatin post-treatment. These effects helped to preserve renal function and Oat3 function and expression. These results indicate that atorvastatin has a renoprotective effect against gentamicin-induced nephrotoxicity by decreasing overoxidation in the kidney, and might be used in conjunction with gentamicin to protect against renal damage.
format Journal
author Krit Jaikumkao
Anchalee Pongchaidecha
Nipon Chattipakorn
Varanuj Chatsudthipong
Sasivimon Promsan
Phatchawan Arjinajarn
Anusorn Lungkaphin
author_facet Krit Jaikumkao
Anchalee Pongchaidecha
Nipon Chattipakorn
Varanuj Chatsudthipong
Sasivimon Promsan
Phatchawan Arjinajarn
Anusorn Lungkaphin
author_sort Krit Jaikumkao
title Atorvastatin improves renal organic anion transporter 3 and renal function in gentamicin-induced nephrotoxicity in rats
title_short Atorvastatin improves renal organic anion transporter 3 and renal function in gentamicin-induced nephrotoxicity in rats
title_full Atorvastatin improves renal organic anion transporter 3 and renal function in gentamicin-induced nephrotoxicity in rats
title_fullStr Atorvastatin improves renal organic anion transporter 3 and renal function in gentamicin-induced nephrotoxicity in rats
title_full_unstemmed Atorvastatin improves renal organic anion transporter 3 and renal function in gentamicin-induced nephrotoxicity in rats
title_sort atorvastatin improves renal organic anion transporter 3 and renal function in gentamicin-induced nephrotoxicity in rats
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84965166758&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/55198
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