Effects of taurine supplementation in parenteral nutrition-associated hepatosteatosis and lidocaine metabolism. A study using isolated rat liver perfusion.
The effects of taurine in parenteral nutrition (PN)-related hepatic dysfunction are controversial. The aims of the present study were to evaluate the effects of taurine on hepatic function and on lidocaine metabolism, using two strengths of taurine (15 and 50 mg/dl) that are present in commercially available preparations. Animals (N > or = 4) were randomly assigned to one of the four 7-day treatment groups: chow-fed (CF); dextrose/amino acids (PN); dextrose/amino acids and taurine, 15 mg/dl (T15); dextrose/amino acids and taurine, 50 mg/dl (T50). Between 40-75% of the animals treated with PN developed steatosis. The origin of steatosis was zonal specific and dependent on taurine treatment. All livers in the CF group had a normal cellular architecture. Lidocaine metabolism was found to be impaired in groups PN, T15, and T50. This was indicated by a significant reduction in the intrinsic clearance values: 70%, 76%, and 85% in groups PN, T15, and T50, respectively (p < 0.05). Metabolites-to-drug ratios indicated that N-dealkylation, m-hydroxylation, and aryl methyl hydroxylation were significantly reduced in all treatment groups; the most pronounced effect was observed in the T50 group. These findings suggest that PN infusion results in impaired liver function, and the reduction of drug elimination rate is exacerbated by the addition of taurine.
Zaman
N
N
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Tam
Y K
YK
Jewell
L D
LD
Coutts
R T
RT
D000596:Amino Acids / Q000032:analysis / Q000097:blood; D000818:Animals; D005234:Fatty Liver / Q000209:etiology* / Q000473:pathology; D005526:Food, Formulated; D008012:Lidocaine / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D010288:Parenteral Nutrition / Q000009:adverse effects*; D010477:Perfusion; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000008:administration & dosage / Q000494:pharmacology*
D000596:Amino Acids; D013654:Taurine; D008012:Lidocaine