Exploring novel pharmacological approaches to attenuate ischemia reperfusion induced renal injury

Abstract

The current study explored the pharmacological approaches to reveal the newlinerenoprotective mechanism of Troxerutin, Quinazoline, and PD146176 using novel newlinepharmacological approaches. newlineThe research design involved the introduction of renal ischemia (60 min.) and newlinereperfusion (24 hr.). Troxerutin, Quinazoline, and PD146176 were administered for 10 newlinemin. before renal ischemia for 60 min. and 24hrs of reperfusion to animals separated newlineinto several groups, so that the Pharmacological treatments would be in the systemic newlinecirculation at the time of onset of reperfusion. LY294002 (a specific inhibitor of newlinePhosphatidyl inositol-3 kinase (PI3K), and 666-15 (a specific inhibitor of cAMP newlineresponse element binding protein (CREB) was administered for elucidating the role of newlineseveral signaling pathways modulated by Pharmacological agents. Numerous kidney newlinefunction tests, biochemical markers, and histopathological alterations were evaluated to newlineobserve the outcome of these Pharmacological treatments. It was demonstrated that newlinePharmacological interventions with the above-mentioned agents reduced the destructive newlineeffects of I/R injury as assessed with regard to various kidney function tests (BUN, newlineSCr, Plasma uric acid, and CrCl), biochemical markers of lipid peroxidation and newlineoxidative stress (TBARS, SAG, 15-HETE, SOD and GSH), inflammation (MPO), and newlineinflammatory markers (TNF-and#593;, IL-1and#946;, IL-6, and NF-and#1179;B), apoptotic markers (proapoptotic newlineproteins like Bcl-2 and apoptotic proteins like caspase 3 and Bax), and newlinehistopathological alterations. We conclude that induced renoprotective benefits with newlinePD146176, Troxerutin, and Quinazoline in all probability, may be the consequence of newlineinhibition of the 15-LOX pathway, activation of PI3K pathway and cAMP/CREB newlinepathway and these treatments could be considered, for further research, as probable newlinedrug inducing renoprotection under clinical conditions. newline