Alterations in renal cortex cation homeostasis during mercuric chloride and gentamicin nephrotoxicity.
To help better understand the role of changes in cellular cation homeostasis in the pathogenesis of renal tubular cell injury, the alterations in cation content of renal cortex and isolated renal cortical mitochondria occurring during models of nephrotoxicity secondary to gentamicin and HgCl2 were determined both during a developing phase of injury prior to the appearance of cell necrosis and after advanced injury when cell necrosis was present. At 3 hr after 5 mg/kg HgCl2 or after 4 daily doses of 100 mg/kg gentamicin, tubular cell integrity was still intact but mitochondrial functional changes were present. There were no alterations of renal cortex tissue electrolytes at this stage in the HgCl2 model but tissue K+, and more prominently, tissue Mg2+ were decreased in the gentamicin model. K+ and Mg2+ contents of isolated mitochondria were slightly reduced after HgCl2. Only K+ content was slightly reduced after gentamicin. No evidence for tissue or mitochondrial Ca2+ overload was present in either model. At 12 hr after 5 mg/kg HgCl2 or after 10 daily 100 mg/kg doses of gentamicin, widespread areas of tubular cell necrosis were present and the function of isolated mitochondria was severely compromised. Tissue electrolytes at this stage of injury in both models were characterized predominantly by a twofold increase in Na+ content and five- to sixfold increases in Ca2+. Isolated mitochondria showed marked decreases in K+ content and marked increases in content of Na+ and Ca2+. These data suggest that neither cellular and mitochondrial Ca2+ overload nor substantial changes in cellular Na+ and K+ homeostasis can be implicated in the early stages of renal tubular cell injury produced by gentamicin and HgCl2.
D000818:Animals; D001806:Blood Urea Nitrogen; D001834:Body Water / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D005839:Gentamicins / Q000633:toxicity*; D006706:Homeostasis / Q000187:drug effects*; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride; D008628:Mercury / Q000633:toxicity*; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D005839:Gentamicins; D011506:Proteins; D008627:Mercuric Chloride; D012964:Sodium; D008628:Mercury; D008274:Magnesium; D011188:Potassium; D002118:Calcium