Inflammation affects ontogeny of L-carnitine hmeostasis mechanisms in the developing rat

ABSTRACT This thesis research involved investigations into the effects of inflammation on maturation of L-carnitine homeostasis in developing rat neonates. The overall hypothesis was an inflammatory stimulus will alter the ontogeny of L-carnitine homeostasis pathways and this depends upon when the inflammatory stimulus occurs in postnatal development. The objective was to investigate the potential effect of inflammation on carnitine transporter expression in different age groups of neonates and evaluation of effect of inflammation on ontogeny and activity of enzymes involved in carnitine biosynthesis and whether this differs depending upon when in postnatal development the inflammatory stimulus occurs. Rat pups at postnatal day 3, 7, and 14 received an intraperitoneal injection of lipopolysaccharide (LPS) at a dose known to cause a febrile reaction in rat neonates. L-Carnitine homeostasis pathways underwent significant ontogenesis during postnatal development in the rat. LPS administration caused a significant decrease in free L-carnitine levels in serum and heart tissue and a decrease in mRNA expression levels of the high affinity carnitine transporter, Octn2, in kidney, heart and intestine at all postnatal ages. Furthermore, significant decreases in mRNA expression levels of key enzymes involved in carnitine biosynthesis was observed, while an increase in carnitine palmitoyltransferase mRNA levels were observed at all postnatal ages. Reductions in butyrobetaine hydroxylase mRNA expression were paralleled by reductions in enzyme activity only at postnatal day 3 and 7. Heart creatine phosphate levels were deceased significantly in LPS treated groups in all postnatal ages; however, ADP and ATP levels were unaffected. Collectively, this research provided experimental evidence for a significant effect of inflammation on changes in L-carnitine homeostasis maturation in early neonatal stages. The maturation of physiological processes may be altered by external factors in early postnatal life