Newborn liver and kidney metabolism as influenced by oxygen toxicity and anorectic drugs

Abstract

Treatment of neonatal rats with 60 mg/kg·d chlorphentermine for 1 wk significantly increased the incorporation of thymidine into renal and hepatic DNA, while a 20 mg/kg·d dose had no marked effect. Both doses of phentermine produced a significant decrease in thymidine incorporation into liver and kidney DNA. In kidney, both anorectics increased the concentration of cyclic AMP, whereas a decrease or no change was noted in liver, suggesting that in this study cyclic AMP may not play a role as a modulator of DNA synthesis. Hyperoxia produced a reduction in the incorporation of thymidine into renal and hepatic DNA accompanied by a rise in cyclic AMP. In general, oxidant exposure of drug‐pretreated animals also resulted in decreased incorporation of thymidine into DNA and elevated cyclic AMP levels. Whereas phentermine and 60 mg/kg chlorphentermine administration to oxidant‐exposed newborns produced a fall in incorporation of thymidine into renal and hepatic DNA, a rise was seen in the case of 20 mg/kg chlorphentermine and oxygen. Prior oxygen exposure followed by 60 mg/kg chlorphentermine increased kidney and liver cyclic AMP, whereas a decrease or no change occurred with phentermine and oxidant. Hyperoxia followed by air resulted in increased incorporation of thymidine into renal and hepatic DNA as well as a fall in cyclic AMP, suggesting that the oxidant‐inflicted alterations were reversible. The evidence indicates that in addition to lung, liver and kidney metabolism of newborns is also subject to oxygen toxicity and that these tissues respond to anorectic drugs in a manner different from that seen in adults.