Oxygen uptake in neonatal rats: a developmental study with particular reference to the effects of chloramphenicol.

Abstract

Extract: Chloramphenicol (CHL) treatment in rats begun 0–2 hr after birth inhibited the increase in oxygen uptake, particularly the metabolic response to cold, during the first neonatal days. In rats treated for 5 days with CHL, a few hours after elimination of the drug from the body the tissue levels of ADP and Pi were significantly higher and the levels of ATP significantly lower than in controls. Furthermore, the presence of more than 0.2 mM free CHL in serum and liver caused a decrease in oxygen consumption and ATP levels and an increase in Pi levels. These changes, progressive with increasing CHL concentrations, appeared to be due to direct interference of CHL with mitochondrial electron transport.Oxygen uptake, as measured in liver slices, increased during the first 2 neonatal days, whereas in slices obtained from adults uptake was lower than in 2–5-day-old animals. In liver slices obtained from rats treated with CHL for 5 days, antimycin-sensitive oxygen consumption was deficient both in the presence of excess ADP and in a hypoxic environment.Oxygen consumption and the steady state reduction levels of cytochrome c were measured in isolated mitochondria with succinate as substrate. According to these studies, the rate-limiting point of oxygen uptake in mitochondria obtained after 5 days of CHL treatment was a deficient phosphorylation site at cytochrome oxidase. On the basis of the previous evidence this was due to selective inhibition of intra-mitochondrial protein synthesis by CHL.Speculation: In rats a rate-limiting point in the neonatal increase in capacity for oxygen uptake is the activity of mitochondrial oxidative phosphorylation. From the resemblances between newborn animals and human infants both in the detrimental effects of CHL and in oxygen uptake in vivo, it seems that the present results can be applied to human development.