Heat shock protein 70 induction and its urinary excretion in a model of acetaminophen nephrotoxicity.
Acetaminophen (APAP) is an analgesic-antipyretic drug widely used in children. In the present study, we used an in vivo model of APAP-induced nephrotoxicity in male Wistar rats. We analyzed whether toxic doses of APAP could induce heat shock protein 70 (HSP70) in the kidney and whether HSP70 could be detected in urine. Renal function and histological evaluation of the kidneys were performed at different times after APAP administration (1,000 mg/kg body weight i.p.). Cellular injury was assessed by Triton X-100 solubilization of Na(+)/K(+) ATPase. Renal and hepatic glutathione levels were also measured. Urinary N-acetyl-beta-D glucosaminidase (NAG) excretion increased 4 h after intoxication. At this time, urea and creatinine were at control levels and a slight degree of histological alteration was detected. Kidney microscopic evaluation, Na(+)/K(+) ATPase solubility, creatinine, and urea levels and NAG excretion did not differ from those of controls 48 h after APAP administration. HSP70 was detected in urine obtained from 4 to 24 h after APAP administration. HSP70 abundance in renal cortex was increased at early time points and 48 h after APAP administration. Urinary HSP70 excretion would be a marker of its renal induction combined with the loss of tubule integrity. NAG would be a suitable early biomarker of APAP-induced nephrotoxicity.
Molinas
Sara M
SM
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rosario, Argentina.
Rosso
Marina
M
Wayllace
Nahuel Z
NZ
Pagotto
Melina A
MA
Pisani
Gerardo B
GB
Monasterolo
Liliana A
LA
Trumper
Laura
L
D000082:Acetaminophen / Q000633:toxicity*; D000118:Acetylglucosaminidase / Q000652:urine; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007677:Kidney Function Tests; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014508:Urea / Q000097:blood
D018712:Analgesics, Non-Narcotic; D018840:HSP70 Heat-Shock Proteins; D000082:Acetaminophen; D014508:Urea; D003404:Creatinine; D000118:Acetylglucosaminidase; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione