Prevention by L-arginine and polyamines of delayed development and embryotoxicity caused by chemically-induced diabetes in rats

Diabetes mellitus induction with alloxan at a dose of 110 mg/kg i.p. in rat s on Day 4 of pregnancy causes delayed development and resorptions as signs of embryotoxicity. In the present study, the administration of human NPH i nsulin at doses of 1 to 5 U/d to rats or 1.0 mL of 10 mM L-arginine for 8 d , starting the day following diabetes induction, prevented embryotoxicity a nd delayed development. Similar results were obtained when the polyamines p utrescine, spermidine, or spermine were administered at doses of 1.0 mt of a 10 mu M solution to each rat daily. However, even though L-arginine and p olyamines prevented adverse effects of severe diabetes on the conceptus, an d caused normalization of glucose, beta-hydroxybutyrate levels remained ele vated. These results support the hypothesis that the mechanisms of normal a nd altered development could be mediated by the action of polyamines. (C) 1 999 Elsevier Science Inc. All rights reserved.