IMPAIRMENT OF CELLULAR REDOX STATUS AND MEMBRANE-PROTEIN ACTIVITIES IN KIDNEYS FROM RATS WITH ISCHEMIC ACUTE-RENAL-FAILURE

Cellular redox status and membrane protein activities were analyzed in kidneys from rats with ischemic acute renal failure (ARF). ARF was in duced by clamping the left renal artery for 50 min. A parallel group o f control animals was processed. In the ischemic group urea plasma lev els were statistically increased as compared with the control group. S tudies employing whole kidney homogenates revealed that ischemia produ ces an increment in lipid peroxidation levels and a reduction in gluta thione concentration and in superoxide dismutase and glutathione perox idase activities. Since lipid peroxidation may alter the function of m embrane proteins we determined succinate cytochrome c reductase (SuccR ), sodium-potassium ATPase (Na-K-ATPase), glucose-6-phosphatase (G-6-P ase) and alkaline phosphatase (ALP) activities in whole renal homogena tes. Only G-6-Pase and ALP activities were modified by ischemia. Since ALP is a brush border membrane (BBM) enzyme and BBM is one of the mai n target structures in ARF, we assessed some parameters of BBM functio nality. ALP, gamma-glutamyl transferase (gamma-GT) and 5'-nucleotidase (5'-NT) showed diminished activities in BBM from ischemic kidneys. Is chemia also modified the V-max of paraaminohippuric acid (PAH) uptake without altering K-m. An increment of lipid peroxidation and membrane fluidity in BBM was observed after the treatment. Total membrane prote ins and protein recoveries in BBM were similar in both experimental gr oups. Sialic acid and sulfhydryl levels were similar in BBM from ische mic kidney and control ones. In summary, ARF induced by renal artery c lamping for 50 min takes place with a significant increase in urea pla sma levels. A decrease in the antioxidant defense system is detected. This induces lipid peroxidation in whole renal tissue, which may justi fy the diminished activities of some membrane enzymes such as G-6-Pase and ALP. A specific analysis of BBM function reveals a significant in crement of lipid peroxidation which may be the cause of an increased m embrane fluidity. This latter parameter might be, at least in part, re sponsible for the damaged function of apical ALP, 5'-NT, gamma-GT and PAH carrier. (C) 1998 Elsevier Science B.V. All rights reserved.