Propylthiouracil attenuates acetaminophen-induced renal damage in the rat.
BACKGROUND
To date, there is no specific antidote to acetaminophen poisoning. Propylthiouracil (PTU) has been shown to be protective against acetaminophen (APAP)-induced liver damage in rats; however, the nephroprotective effect of propylthiouracil has not been studied yet.


METHODS
In order to verify this, rats were given different doses of PTU (100, 200 or 400 mg/kg per body weight, orally) 1 h before a nephrotoxic dose of APAP (1,000 mg/kg per body weight, intraperitoneally (i.p.)).


RESULTS
Propylthiouracil pretreatment significantly reduced APAP-induced nephrotoxicity in a dose-dependant manner, as evidenced by reduction in plasma creatinine and by amelioration of renal pathology (interstitial congestion, tubular cell degeneration and necrosis).


CONCLUSIONS
The mechanism of protection by PTU is probably not due to the sparing effect of non-protein thiol (approximately 95% of which is reduced glutathione), as similar depletion of renal glutathione was observed regardless of PTU pretreatment; other mechanisms are suggested.
Abraham
Premila
P
Department of Biochemistry, Christian Medical College, Bagayam, Vellore, India. premilaabraham@yahoo.com
Kanakasabapathy
Indirani
I
Dian
Bondu Joseph
BJ
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D011441:Propylthiouracil / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014508:Urea / Q000097:blood
D008054:Lipid Peroxides; D013438:Sulfhydryl Compounds; D000082:Acetaminophen; D011441:Propylthiouracil; D014508:Urea; D003404:Creatinine