Increase in the renal damage induced by paracetamol in rats exposed to ethanol translactationally.
Administration of ethanol (8%) or acetone (1%) to nursing dams in the drinking water, for 10 days, increased the nephrotoxicity of paracetamol (APAP) in the 14-day-old lactating offspring. The percentage of proximal tubular cells with evidence of necrotic damage in male rats was higher in those animals that received APAP (500 mg/kg, i.p.) and whose nursing rats were exposed to ethanol (25. 0 +/- 8.4%) or acetone (17.2 +/- 1.2%), than in the group treated with APAP alone (10.6 +/- 1.6%). The activity of urinary N-acetylglucuronidase was also significantly higher in the rats exposed translactationally to ethanol or acetone than in animals treated with the APAP alone. Nephrotoxicity showed a sexual dimorphic pattern with a higher toxicity in male than in female rats. The percentage of necrotic tubules in the male rats not exposed to inductor was 10.6 +/- 1.6%, and in female rats 5.0 +/- 1.4% (p < 0. 05). Animals exposed to ethanol or acetone and treated with APAP showed less weight gain than the group treated only with APAP. Our results suggest that renal toxicity is enhanced in the nursing animals that were exposed, via maternal milk, to ethanol or acetone (inductors of cytochrome P4502E1), than in the control animals. This circumstance may be relevant in alcoholic women while they are lactating.
Llamas
J
J
Physiology and Pharmacology Department, Universidad Autónoma de Aguascalientes, México, D.F., Mexico.
Martínez Ma
C
C
Jaramillo-Juárez
F
F
Muñoz-Fernández
L
L
Bustos
L
L
Reyes
J L
JL
D000082:Acetaminophen / Q000506:poisoning*; D000096:Acetone / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000833:Animals, Suckling; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D005966:Glucuronidase / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007774:Lactation / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics
D000096:Acetone; D000082:Acetaminophen; D000431:Ethanol; D005966:Glucuronidase