Nitrooleic Acid Protects against Cisplatin Nephropathy: Role of COX-2/mPGES-1/PGE2 Cascade

Nitrooleic acid (OA-NO2) is an endogenous lipid product which has novel signaling properties, particularly the activation of peroxisome proliferator-activated receptors. The current study aimed to evaluate the protective effects of OA-NO2 against cisplatin-induced kidney injury in mice. Mice were pr...

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Main Authors: Haiping Wang, Zhanjun Jia, Jing Sun, Liang Xu, Bing Zhao, Kezhou Yu, Meng Yang, Tianxin Yang, Rong Wang
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2015/293474
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author Haiping Wang
Zhanjun Jia
Jing Sun
Liang Xu
Bing Zhao
Kezhou Yu
Meng Yang
Tianxin Yang
Rong Wang
author_facet Haiping Wang
Zhanjun Jia
Jing Sun
Liang Xu
Bing Zhao
Kezhou Yu
Meng Yang
Tianxin Yang
Rong Wang
author_sort Haiping Wang
collection DOAJ
description Nitrooleic acid (OA-NO2) is an endogenous lipid product which has novel signaling properties, particularly the activation of peroxisome proliferator-activated receptors. The current study aimed to evaluate the protective effects of OA-NO2 against cisplatin-induced kidney injury in mice. Mice were pretreated with OA-NO2 for 48 h before cisplatin administration, and the cisplatin-caused nephrotoxicity was evaluated. After the cisplatin treatment (72 h), the vehicle-treated mice displayed renal dysfunction, as evidenced by the elevated plasma urea and creatinine, which was consistent with the histological damage, such as tubular necrosis, dilation, protein cast, and desquamation of epithelial cells. In contrast, the severity of the renal dysfunction and histological change were reduced in the OA-NO2 pretreated mice. The renal COX-2 and mPGES-1 mRNAs and their respective proteins expression, together with the renal PGE2 amounts, were induced by the cisplatin treatment, but their initiation was reduced by OA-NO2. Moreover, the circulating TNF-α, renal TNF-α, IL-1β, MCP-1, ICAM-1, and VACAM-1 mRNA levels were higher in the cisplatin-treated mice, compared with the controls, but they were attenuated in the OA-NO2 pretreatment group. In summary, the pretreatment with OA-NO2 remarkably ameliorated the cisplatin-induced kidney injury in mice, possibly via the inhibition of the inflammatory response, associated with the COX-2/mPGES-1/PGE2 cascade.
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spelling doaj-art-ca293a0d389045dfb505e9d82884b7e52025-08-20T02:20:01ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/293474293474Nitrooleic Acid Protects against Cisplatin Nephropathy: Role of COX-2/mPGES-1/PGE2 CascadeHaiping Wang0Zhanjun Jia1Jing Sun2Liang Xu3Bing Zhao4Kezhou Yu5Meng Yang6Tianxin Yang7Rong Wang8Department of Nephrology, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong 250013, ChinaDepartment of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT 84112, USADepartment of Nephrology, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong 250013, ChinaDepartment of Nephrology, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong 250013, ChinaDepartment of Nephrology, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong 250013, ChinaDepartment of Nephrology, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong 250013, ChinaDepartment of Nephrology, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong 250013, ChinaDepartment of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT 84112, USADepartment of Nephrology, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong 250013, ChinaNitrooleic acid (OA-NO2) is an endogenous lipid product which has novel signaling properties, particularly the activation of peroxisome proliferator-activated receptors. The current study aimed to evaluate the protective effects of OA-NO2 against cisplatin-induced kidney injury in mice. Mice were pretreated with OA-NO2 for 48 h before cisplatin administration, and the cisplatin-caused nephrotoxicity was evaluated. After the cisplatin treatment (72 h), the vehicle-treated mice displayed renal dysfunction, as evidenced by the elevated plasma urea and creatinine, which was consistent with the histological damage, such as tubular necrosis, dilation, protein cast, and desquamation of epithelial cells. In contrast, the severity of the renal dysfunction and histological change were reduced in the OA-NO2 pretreated mice. The renal COX-2 and mPGES-1 mRNAs and their respective proteins expression, together with the renal PGE2 amounts, were induced by the cisplatin treatment, but their initiation was reduced by OA-NO2. Moreover, the circulating TNF-α, renal TNF-α, IL-1β, MCP-1, ICAM-1, and VACAM-1 mRNA levels were higher in the cisplatin-treated mice, compared with the controls, but they were attenuated in the OA-NO2 pretreatment group. In summary, the pretreatment with OA-NO2 remarkably ameliorated the cisplatin-induced kidney injury in mice, possibly via the inhibition of the inflammatory response, associated with the COX-2/mPGES-1/PGE2 cascade.http://dx.doi.org/10.1155/2015/293474
spellingShingle Haiping Wang
Zhanjun Jia
Jing Sun
Liang Xu
Bing Zhao
Kezhou Yu
Meng Yang
Tianxin Yang
Rong Wang
Nitrooleic Acid Protects against Cisplatin Nephropathy: Role of COX-2/mPGES-1/PGE2 Cascade
Mediators of Inflammation
title Nitrooleic Acid Protects against Cisplatin Nephropathy: Role of COX-2/mPGES-1/PGE2 Cascade
title_full Nitrooleic Acid Protects against Cisplatin Nephropathy: Role of COX-2/mPGES-1/PGE2 Cascade
title_fullStr Nitrooleic Acid Protects against Cisplatin Nephropathy: Role of COX-2/mPGES-1/PGE2 Cascade
title_full_unstemmed Nitrooleic Acid Protects against Cisplatin Nephropathy: Role of COX-2/mPGES-1/PGE2 Cascade
title_short Nitrooleic Acid Protects against Cisplatin Nephropathy: Role of COX-2/mPGES-1/PGE2 Cascade
title_sort nitrooleic acid protects against cisplatin nephropathy role of cox 2 mpges 1 pge2 cascade
url http://dx.doi.org/10.1155/2015/293474
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