| First Author | Jia Z | Year | 2011 |
| Journal | Kidney Int | Volume | 79 |
| Issue | 1 | Pages | 77-88 |
| PubMed ID | 20844471 | Mgi Jnum | J:186895 |
| Mgi Id | MGI:5433471 | Doi | 10.1038/ki.2010.331 |
| Citation | Jia Z, et al. (2011) Amelioration of cisplatin nephrotoxicity by genetic or pharmacologic blockade of prostaglandin synthesis. Kidney Int 79(1):77-88 |
| abstractText | Nephrotoxicity is a common complication of cisplatin chemotherapy that limits its clinical use. Here, we determined whether arachidonic acid metabolism has a role in the pathogenesis of cisplatin nephrotoxicity in mice. Three days following cisplatin injection, wild-type mice displayed renal functional and structural abnormalities consistent with nephrotoxicity accompanied by elevated circulating and renal levels of TNF-alpha and renal levels of IL-1beta, subunits of NADPH oxidase, thiobarbituric acid-reactive substances, and PGE(2). These indices of kidney injury, inflammation, oxidative stress, and arachidonate metabolism were all diminished in microsomal prostaglandin E synthase-1 (mPGES-1) null mice; a phenotype recapitulated by treatment of wild-type mice with the COX-2 inhibitor celecoxib. Following cisplatin administration, there was paralleled induction of COX-2 and mPGES-1 in renal parenchymal cells. Interestingly, mPGES-1 null mice were not protected from acute kidney injury caused by ischemia-reperfusion or endotoxin. Hence, our results suggest the activation of COX-2/mPGES-1 pathway in renal parenchymal cells may selectively mediate cisplatin-induced renal injury. This may offer a novel therapeutic target for management of the adverse effect of cisplatin chemotherapy. |
