Hepatic Biotransformation Rate in Calves Fed Food Ra Tions with Protein or Carbohydrate Supplements

Janus K .. Z. Muszczyriski, W. F. Skrzypczak: HepaticBiotralls!ormationRate in Call'esjed Food Rations with Protein or Carbohydrate Slipplemellls. Acta vet. Brno 1996, 65: 123-13 I. The purpose of the study was to evaluate (on the basis of pharmacokinetics of antipyrine) the hepatic biotransformation rate in calves in neonatal period. The calves received supplementary casein or glucose in their food ration. It was found that an increased protein content in the diet significantly increased the hepatic biotransformation rate as indirectly indicated by the monooxygenase activity linked to cytochrome P450. Increased carbohydrate content in the diet produced an opposite effect upon the activity of the system. From these results it can also be concluded that a high-protein diet would increase whereas a high-carbohydrate diet would decrease the metabolism of other of drugs in calves, provided they would undergo the same biotransformation process as antipyrine does. AllIipyrine. neonatal period. casein. glucose. liver. MFO system The liver is responsible for the greater part of the metabolism of a number of drugs and endogenous substrates via the cytochrome P-450 dependent hepatic microsomal monooxygenase(MFO)system(Oanhof and Teunissen 1984; Poulsen and Loft 1988; Viktorov and Rybak 1990; Hartleb 1991). Antipyrine is widely used as a model substrate for cytochrome PA50 dependent metabolism (P 0 u I sen and Loft 1988; Loft 1990). Antipyrine is eliminated primarily via hepatic metabolism. has a low intrinsic clearance and is negligibly bound to tissue and plasma proteins (0 a n h 0 f and T e u n iss e n 1984; Loft 1990; Jan u s et al. 1991). The compound is almost completely metabolized in the liver by at least three oxidative reactions with rapid renal elimination of thesemetabolites(Viktorov and Rybak a1.1990; Hartleb 1991).Estimatesofhalflife and metabolic clearance of antipyrine have therefore been used to assess the drug metabolizing activity of the liver in man and animals and its modification by genetic and multiple environmental factors (penno and Vesel I 1983; Oanhof and Teunissen 1984; Vesel I 1984; Kalow 1987; Poulsen and Loft 1988; Loft 1990). The effects of changes in dietary macronutrient composition on the hepatic microsomal enzymes have been studied extensively in man and laboratory animals (Campbell and Hayes 1976; Campbell 1977; Anderson et al. 1979; Krishnaswamy et al. 1984; Alvares etal. 1986; Bidlack etal. 1986; Young and Yoo 1988; Pantuck et al. 1989; But I e rand 0 aut e r man n 1990; Pan t u c k et al. 1991). These studies show that protein and carbohydrate content in diet influence the activities of these enzymes. The aim of this study was to determine hepatic biotransformation rate in neonatal calves that received supplementary casein or glucose in their food ration. On the basis of antipyrine test an attempt is made to explain whether, and if so, to what extent the increase of protein or carbohydrate content in the diet influenced the activity of hepatic microsomal monooxygenases in young calves.