The action of n-propyl gallate on gluconeogenesis and oxygen uptake in the rat liver.
In the present study the metabolic actions of n-propyl gallate on hepatic gluconeogenesis, oxygen uptake and related parameters were investigated. Experiments were done in the isolated perfused rat liver. n-Propyl gallate inhibited gluconeogenesis and stimulated oxygen uptake at concentrations up to 200 microM. The inhibitory effects on lactate gluconeogenesis (ED(50) 86.4 microM) and alanine gluconeogenesis were considerably more pronounced than those on glycerol and fructose gluconeogenesis. n-Propyl gallate also stimulated oxygen uptake in both the mitochondrial (63%) and microsomal (37%) electron transport chains. The first one is due mainly to the oxidation of n-propanol, as a metabolite of the first step of n-propyl gallate transformation. The second one results from a direct stimulation of the microsomal electron transport chain. n-Propyl gallate inhibited pyruvate carboxylation (ED(50) 142.2 microM) in consequence of an inhibition of pyruvate transport into the mitochondria an effect not found for gallic acid. This is probably the main cause for glucose output inhibition. Secondary causes are (1) deviation of intermediates for the production of NADPH to be used in microsomal electron transport; (2) deviation of glucose 6-phosphate for glucuronidation reactions; (3) gluconeogenesis inhibition by n-propanol, produced intracellularly from n-propyl gallate. Inhibition of mitochondrial energy metabolism is not significant in the range up to 200 microM, as indicated by the very small effect on the cellular ATP levels (5% decreased). n-Propyl gallate can be considered a kind of metabolic effector, whose actions on the liver metabolism are relatively mild although they can become harmful for the organ and the whole organism at high doses and concentrations.
Eler
Gabrielle Jacklin
GJ
Department of Biochemistry, University of Maringá, 87020900 Maringá, Brazil.
Peralta
Rosane Marina
RM
Bracht
Adelar
A
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005943:Gluconeogenesis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D011435:Propyl Gallate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D011435:Propyl Gallate; D010100:Oxygen