Tags

Type your tag names separated by a space and hit enter

Amelioration of Renal Inflammation, Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity.
PLoS One. 2016; 11(10):e0164528.Plos

Abstract

Gentamicin is a commonly used aminoglycoside antibiotic. However, its therapeutic use is limited by its nephrotoxicity. The mechanisms of gentamicin-induced nephrotoxicity are principally from renal inflammation and oxidative stress. Since atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, exerts lipid-lowering effects, antioxidant, anti-inflammatory as well as anti-apoptotic effects, this study aimed to investigate the protective effects of atorvastatin against gentamicin-induced nephrotoxicity. Male Sprague Dawley rats were used and nephrotoxicity was induced by intraperitoneal injection of gentamicin, 100 mg/kg/day, for 15 days. Atorvastatin, 10 mg/kg/day, was administered by orally gavage 30 min before gentamicin injection on day 1 to 15 (pretreatment) or on day 10 to15 (delayed treatment). For only atorvastatin treatment group, it was given on day 1 to 15. At the end of the experiment, kidney weight, blood urea nitrogen and serum creatinine as well as renal inflammation (NF-κB, TNFαR1, IL-6 and iNOS), renal fibrosis (TGFβ1), ER stress (calpain, GRP78, CHOP, and caspase 12) and apoptotic markers (cleaved caspase-3, Bax, and Bcl-2) as well as TUNEL assay were determined. Gentamicin-induced nephrotoxicity was confirmed by marked elevations in serum urea and creatinine, kidney hypertrophy, renal inflammation, fibrosis, ER stress and apoptosis and attenuation of creatinine clearance. Atorvastatin pre and delayed treatment significantly improved renal function and decreased renal NF-κB, TNFαR1, IL-6, iNOS and TGFβ1 expressions. They also attenuated calpain, GRP78, CHOP, caspase 12, Bax, and increased Bcl-2 expressions in gentamicin-treated rat. These results indicate that atorvastatin treatment could attenuate gentamicin-induced nephrotoxicity in rats, substantiated by the reduction of inflammation, ER stress and apoptosis. The effect of atorvastatin in protecting from renal damage induced by gentamicin seems to be more effective when it beginning given along with gentamicin or pretreatment.

Authors+Show Affiliations

Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. School of Medicine, Mae Fah Luang University, Chiang Rai, Thailand.Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand.Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27727327

Citation

Jaikumkao, Krit, et al. "Amelioration of Renal Inflammation, Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity." PloS One, vol. 11, no. 10, 2016, pp. e0164528.
Jaikumkao K, Pongchaidecha A, Thongnak LO, et al. Amelioration of Renal Inflammation, Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity. PLoS One. 2016;11(10):e0164528.
Jaikumkao, K., Pongchaidecha, A., Thongnak, L. O., Wanchai, K., Arjinajarn, P., Chatsudthipong, V., Chattipakorn, N., & Lungkaphin, A. (2016). Amelioration of Renal Inflammation, Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity. PloS One, 11(10), e0164528. https://doi.org/10.1371/journal.pone.0164528
Jaikumkao K, et al. Amelioration of Renal Inflammation, Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity. PLoS One. 2016;11(10):e0164528. PubMed PMID: 27727327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amelioration of Renal Inflammation, Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity. AU - Jaikumkao,Krit, AU - Pongchaidecha,Anchalee, AU - Thongnak,La-Ongdao, AU - Wanchai,Keerati, AU - Arjinajarn,Phatchawan, AU - Chatsudthipong,Varanuj, AU - Chattipakorn,Nipon, AU - Lungkaphin,Anusorn, Y1 - 2016/10/11/ PY - 2016/05/24/received PY - 2016/09/27/accepted PY - 2016/10/12/entrez PY - 2016/10/12/pubmed PY - 2017/5/10/medline SP - e0164528 EP - e0164528 JF - PloS one JO - PLoS One VL - 11 IS - 10 N2 - Gentamicin is a commonly used aminoglycoside antibiotic. However, its therapeutic use is limited by its nephrotoxicity. The mechanisms of gentamicin-induced nephrotoxicity are principally from renal inflammation and oxidative stress. Since atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, exerts lipid-lowering effects, antioxidant, anti-inflammatory as well as anti-apoptotic effects, this study aimed to investigate the protective effects of atorvastatin against gentamicin-induced nephrotoxicity. Male Sprague Dawley rats were used and nephrotoxicity was induced by intraperitoneal injection of gentamicin, 100 mg/kg/day, for 15 days. Atorvastatin, 10 mg/kg/day, was administered by orally gavage 30 min before gentamicin injection on day 1 to 15 (pretreatment) or on day 10 to15 (delayed treatment). For only atorvastatin treatment group, it was given on day 1 to 15. At the end of the experiment, kidney weight, blood urea nitrogen and serum creatinine as well as renal inflammation (NF-κB, TNFαR1, IL-6 and iNOS), renal fibrosis (TGFβ1), ER stress (calpain, GRP78, CHOP, and caspase 12) and apoptotic markers (cleaved caspase-3, Bax, and Bcl-2) as well as TUNEL assay were determined. Gentamicin-induced nephrotoxicity was confirmed by marked elevations in serum urea and creatinine, kidney hypertrophy, renal inflammation, fibrosis, ER stress and apoptosis and attenuation of creatinine clearance. Atorvastatin pre and delayed treatment significantly improved renal function and decreased renal NF-κB, TNFαR1, IL-6, iNOS and TGFβ1 expressions. They also attenuated calpain, GRP78, CHOP, caspase 12, Bax, and increased Bcl-2 expressions in gentamicin-treated rat. These results indicate that atorvastatin treatment could attenuate gentamicin-induced nephrotoxicity in rats, substantiated by the reduction of inflammation, ER stress and apoptosis. The effect of atorvastatin in protecting from renal damage induced by gentamicin seems to be more effective when it beginning given along with gentamicin or pretreatment. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/27727327/Amelioration_of_Renal_Inflammation_Endoplasmic_Reticulum_Stress_and_Apoptosis_Underlies_the_Protective_Effect_of_Low_Dosage_of_Atorvastatin_in_Gentamicin_Induced_Nephrotoxicity_ L2 - https://dx.plos.org/10.1371/journal.pone.0164528 DB - PRIME DP - Unbound Medicine ER -