Influence of hydrocortisone on gentamicin-induced nephrotoxicity in rats.
Many risk factors associated with aminoglycoside nephrotoxicity have been identified in humans and experimental animals. They include an initial high rate of creatinine clearance, high initial peak levels in serum, age, sex, duration of therapy, liver disease, and renal infection. The concomitant administration of steroids has never been investigated. We evaluated the role of hydrocortisone on gentamicin-induced nephroxicity in a model of infused rats. We showed that hydrocortisone given over 3 days after the infusion did not modify the gentamicin half-life in the renal cortex, gentamicin-induced lysosomal phospholipidosis, or histopathology but did reduce significantly the 3H/DNA ratio on day 4 after gentamicin infusion. We concluded that hydrocortisone interferes with the postnecrotic cellular regeneration process, an important step that is responsible for the recovery of normal kidney structure following toxic injuries associated with aminoglycoside therapy.
Beauchamp
D
D
Service d'Infectiologie, Le Centre Hospitalier de l'Université Laval, Ste.-Foy, Quebec, Canada.
Pettigrew
M
M
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair; D005260:Female; D005839:Gentamicins / Q000493:pharmacokinetics / Q000633:toxicity*; D006651:Histocytochemistry; D006854:Hydrocortisone / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects*; D007672:Kidney Cortex / Q000378:metabolism / Q000648:ultrastructure; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains
D005839:Gentamicins; D004247:DNA; D006854:Hydrocortisone