BACKGROUND: In a prior study the 21-aminosteroid (lazaroid) U74389F provided in vivo protection from oxidative stress when used as a preventive therapy in ischemia-reperfusion injury in the kidney. As the cell membrane is the principal site for lipoperoxidation, in the current study the very lipophilic 2-methylaminochroman U83836E, a recently developed lazaroid, was administered to rats at 3 mg/kg before renal ischemia-reperfusion. In addition to the biochemical parameters, the renal function and the histological appearance were carefully evaluated. METHODS: Glutathione, adenine nucleotides and lipid peroxidation products were determined in kidneys reperfused for 2 and 24 hours after 90 minutes of ischemia. Renal function was assessed by plasma creatinine, and renal injury by histological examination. RESULTS: Reperfusion-induced glutathione oxidation, expressed as an oxidized-to-total glutathione ratio, was significantly attenuated both after 2 and 24 hours of reperfusion by treatment with U83836E. Adenosine triphosphate (ATP) was still significantly depleted after 24 hours in the control group, while at the same time treated animals had already recovered to baseline values. Lipid peroxidation products were significantly lower in lazaroid-groups both after 2 and 24 hours of reperfusion. Renal function after 24 hours of reperfusion was notably better in the treated rats. Histological examination confirmed the protective action of the drug. After 24 hours the control group showed large areas of parenchymal hemorrhage and necrosis with dilated tubules and blood vessel thrombosis, while treated animals showed small necrotic areas with a background of mild interstitial inflammatory cells. CONCLUSIONS: Our results suggest that there is a protective effect of U83836E in ischemia-reperfusion injury, in that tissue damage due to oxidative stress is reduced, thus ameliorating renal function impairment.
BACKGROUND: In a prior study the 21-aminosteroid (lazaroid) U74389F provided in vivo protection from oxidative stress when used as a preventive therapy in ischemia-reperfusion injury in the kidney. As the cell membrane is the principal site for lipoperoxidation, in the current study the very lipophilic 2-methylaminochromanU83836E, a recently developed lazaroid, was administered to rats at 3 mg/kg before renal ischemia-reperfusion. In addition to the biochemical parameters, the renal function and the histological appearance were carefully evaluated. METHODS:Glutathione, adenine nucleotides and lipid peroxidation products were determined in kidneys reperfused for 2 and 24 hours after 90 minutes of ischemia. Renal function was assessed by plasma creatinine, and renal injury by histological examination. RESULTS: Reperfusion-induced glutathione oxidation, expressed as an oxidized-to-total glutathione ratio, was significantly attenuated both after 2 and 24 hours of reperfusion by treatment with U83836E. Adenosine triphosphate (ATP) was still significantly depleted after 24 hours in the control group, while at the same time treated animals had already recovered to baseline values. Lipid peroxidation products were significantly lower in lazaroid-groups both after 2 and 24 hours of reperfusion. Renal function after 24 hours of reperfusion was notably better in the treated rats. Histological examination confirmed the protective action of the drug. After 24 hours the control group showed large areas of parenchymal hemorrhage and necrosis with dilated tubules and blood vessel thrombosis, while treated animals showed small necrotic areas with a background of mild interstitial inflammatory cells. CONCLUSIONS: Our results suggest that there is a protective effect of U83836E in ischemia-reperfusion injury, in that tissue damage due to oxidative stress is reduced, thus ameliorating renal function impairment.
Authors: Hazel H Szeto; Shaoyi Liu; Yi Soong; Dunli Wu; Shaun F Darrah; Feng-Ying Cheng; Zhihong Zhao; Michael Ganger; Clara Y Tow; Surya V Seshan Journal: J Am Soc Nephrol Date: 2011-05-05 Impact factor: 10.121