Renal and hepatic nucleic acid metabolism in neonates: relation to experimental duration, chlorphentermine dose as well as subsequent withdrawal.
Daily oral administration of either 20, 40 or 60 mg/kg chlorphentermine for 7 days significantly increased liver and kidney DNA levels, which were not elevated further even after a 3 week treatment period. Although cessation of drug administration for 3 weeks resulted in a return of hepatic DNA levels to control values, a rise in renal DNA was still observed after this withdrawal period. Whereas 20 mg/kg chlorphentermine for 7 days failed to markedly alter the incorporation of thymidine into kidney and liver DNA, significant enhancement was noted in neonates receiving 40 or 60 mg/kg drug and quantitatively greater incorporation occurred when the agent was given for 21 days. While a signficant augmentation in nucleic acids synthesis was seen 1 week after animals were removed from 40 or 60 mg/kg anorectic, a restoration to control levels occurred after a 3 week abstinence period. Treatment with 20 mg/kg for 1 week followed by withdrawal resulted in a significant rise in the incorporation of thymidine into renal and hepatic DNA. In contrast, drug administration for 3 weeks followed by 21 days abstinence resulted in a return to control levels in the incorporation of thymidine into kidney and liver DNA, except for renal tissue removed from 20 mg/kg. Our data demonstrate that the chlorphentermine-induced alterations in renal and hepatic DNA metabolism are dose-dependent, related to duration of exposure as well as reversible.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002745:Chlorphentermine / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010645:Phentermine / Q000031:analogs & derivatives*; D011247:Pregnancy; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D004247:DNA; D010645:Phentermine; D002745:Chlorphentermine; D013936:Thymidine