Neonatal animals metabolism

Metabolism may be mediated by intestinal microflora, epithelial enzymes, or liver enzymes preceding entry into the systemic circulation. Chloramphenicol is well absorbed when administered orally to calves less than 1 week old, but it is inactivated by microflora when administered to ruminants. Similar observations have been made after oral administration of amoxicillin, ampicillin, and cephalexin therapy in young calves (11). On the other hand, trimethoprim, which is extensively metabolized in the liver and may undergo some metabolism in the rumen, shows higher systemic availability in the newborn calf and kid, due probably to the lower metabolic activity in the neonatal animal. 

Chemicals that require metabolic activation may be less toxic in neonatal animals as a result of reduced levels of enzyme activity. However levels of protection may also be reduced. 

In the rat, development to adult levels of activity takes about 30 days after which levels decline toward old age. In humans, however, hydroxylase activity increases up to the age of 6 years, reaching levels greater than those in the adult, which only decrease after sexual maturation. Thus the elimination of antipyrine and theophylline was found to be greater in children than in adults. It should be noted, however, that proportions of isoenzymes may be very different in neonates from the adult animal, and the development of the isoenzymes may be different. Thus, in the rat there seem to be four types of development for phase 1 metabolizing enzymes linear increase from birth to adulthood, type A (aniline 4-hydroxylation) low levels until weaning, then an increase to adult levels, type B (N-demethylation) rapid development after birth followed by rapid decline to low levels in adulthood, type C (hydroxylation of 4-methylcoumarin) and rapid increase after birth to a maximum and then decline to adult levels, type D. Patterns of development may be different between sexes as well as between species. For example, in the rat, steroid 16-a-hydroxylase activity toward androst-4-ene-3,17-dione develops in type B fashion in both males and females, but in females, activity starts to disappear at 30 days of age and is undetectable by 40 days. It seems that the monooxygenase system develops largely as a unit, with the rate dependent on species and sex of the animal and the particular substrate. 

A systematic comparison of the available information on age-dependent maturation of metabolic and elimination processes as well as the toxicokinetics of chemicals in developing neonatal and young animals with that in infants and children can be found elsewhere (Gladtke, 1973 Stewart Hampton, 1987 Crom, 1994 Renwick, 1998 Clewell et al., 2002 Alcorn McNamara, 2003 Kearns et al., 2003 de Zwart et al., 2004 Ginsberg et al., 2004c). Table 2 summarizes the age dependency of toxicokinetic processes and determinants in children compared with adults. 

The essentiality of manganese (Mn) for animals was established in 1931 by Orent and McCollum (1) who reported that this element is required for normal reproduction in the rat, and Kemmerer and colleagues (2) who showed that it was necessary for normal growth and reproduction in the mouse. Since then several investigators have verified the critical need of this nutrient for normal development (3). Manifestations of perinatal Mn deficiency in experimental animals include neonatal death, impaired growth, skeletal abnormalities, depressed reproductive function, congenital ataxia, and defects in protein, carbohydrate and lipid metabolism. 

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