title: NQDI 1, an inhibitor of ASK1 attenuates acute ischemic renal injury by modulating oxidative stress and cell death.
abstract: Apoptosis signal-regulating kinase 1 (ASK1) is among the signaling events that lead to postischemic cell death. Inhibition of ASK1 pathway protected hearts from ischemic damage. The present study evaluated the renal protective effects of NQDI 1, an inhibitor of ASK1, in an animal model of acute ischemic renal failure. Male Wistar rats were subjected to right nephrectomy and clamping of left renal pedicle for 45 min, or sham operation. The administration of NQDI 1 attenuated renal dysfunction and histological changes characteristic for renal ischemia/reperfusion injury (IRI). Apoptosis of renal tissues, as detected by TUNEL staining, was also reduced together with p53 protein expression, and renal levels of MDA and SOD with NQDI 1 administration and BCL2 was up regulated. In conclusion, inhibition of ASK1 is of therapeutic potential against acute ischemic renal injury. Its protective effects are mediated via inhibition of apoptosis and oxidative stress.
authors: Physiology Department, Medical College & King Khalid University Hospital, King Saud University, P.O.BOX 2925(29), Riyadh 11461, Saudi Arabia. emaneleter@yahoo.com.
authors: Eman
authors: E
authors: El Eter
mesh_terms: D000818:Animals; D001060:Aporphines / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D048848:MAP Kinase Kinase Kinase 5 / Q000037:antagonists & inhibitors*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology*
chemical_list: C000592751:2,7-dioxo-2,7-dihydro-3H-naphtho(1,2,3-de)quinoline-1-carboxylate; D001060:Aporphines; D004791:Enzyme Inhibitors; D011804:Quinolines; D048848:MAP Kinase Kinase Kinase 5