[Pathophysiological mechanism of ischemic acute renal failure: protective effect of coenzyme Q10, Ca channel blocker, superoxide dismutase and protease inhibitor against ischemic acute renal failure].
Ischemic insult has been considered a cause of cellular injuries under certain circumstance, such as the disturbance of energy metabolism, the alternation of calcium homeostasis, the production of oxygen radical and the release of lysosomal protease. The present study was designed to clarify the pathophysiological effects of coenzyme Q10 (CoQ10), diltiazem, superoxide dismutase (SOD) and urinastatin on the development and progression of ischemic acute renal failure (IARF) of the rat. At 24 hours after reflow following 45 minutes ischemia, serum urea nitrogen, creatinine and fractional excretion of sodium were 99.3 mg/dl, 3.14 mg/dl, 5.95% respectively, in non-treated IARF rats. Renal ATP content was reduced to 0.91 micrograms/mg. prot. from 10.59 micrograms/mg. prot. at 10 minutes after ischemic insult, and remained at almost the same level throughout the entire 45 minutes ischemia. Although the subsequent blood reflow resulted in the recovery of ATP content, it was up to 50% of normal level at 24 hours after reflow following 45 minutes ischemia. During the ischemic period, the pathological changes were mild, whereas, after reflow, tissue involvement was mainly localized in the S3 segment of the proximal tubule. Major alteration were the loss of brush border, high amplitude swelling of mitochondria with matrical densities and fragmentation of the epithelial cell. At 24 hours after reflow, it was observed that renal function was superior in IARF rats treated with CoQ10, diltiazem, SOD and urinastatin. The treated rats also had higher ATP contents and showed less pathological changes than non-treated rats. Among these inhibitory agents, diltiazem exerted the most reliable effect. From these results, it was concluded that IARF was obviously caused by such pathophysiological mechanisms as mentioned above. Especially, Ca influx into the cells is one of the most important factors on pathogenesis of IARF.
Higuchi
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D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003067:Coenzymes; D004110:Diltiazem / Q000494:pharmacology*; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000494:pharmacology*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
D003067:Coenzymes; D006023:Glycoproteins; D014361:Trypsin Inhibitors; D014451:Ubiquinone; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; D004110:Diltiazem; C024989:coenzyme Q10; C028665:urinastatin; D002118:Calcium