The action of n-propyl gallate on gluconeogenesis and oxygen uptake in the rat liver

Abstract

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.

Propyl gallate and butylated hydroxytoluene influence the accumulation of saturated fatty acids, omega-3 fatty acid and carotenoids in thraustochytrids

“…Acetyl-CoA is required as a precursor for fatty acid synthase and HMGCoA synthase, and acetyl-CoA supply depends on pyruvate (Ratledge, 2004). Propyl gallate is reported to block the transport of pyruvate from the cytoplasm to mitochondria (Eler et al, 2009). Propyl gallate is also reported to slow respiration in the cell (Eler et al, 2009).…”

“…Propyl gallate is reported to block the transport of pyruvate from the cytoplasm to mitochondria (Eler et al, 2009). Propyl gallate is also reported to slow respiration in the cell (Eler et al, 2009). However, higher doses of propyl gallate (up to 2 mM) will completely block the transport of pyruvate from the cytoplasm to mitochondria, causing cellular ATP depletion and cell death (Nakagawa, Moldéus, & Moore, 1996;Nakagawa & Tayama, 1998).…”

“…Propyl gallate, a well-known antioxidant used in the food industry as a preservative, is also reported to block pyruvate transport into mitochondria and is also a non-competitive inhibitor of Δ5 and Δ6 desaturase enzymes, potentially changing the fatty acid profile in microorganisms including thrautochytrids (Eler, Peralta, & Bracht, 2009;Kawashima, Akimoto, Shirasaka, & Shimizu, 1996).Therefore, we chose to study of effects of propyl gallate, and the antioxidant butylated hydroxytoluene (BHT), on thraustochytrids fermentation to determine the impact on DHA productivity, using the strain designated Schizochytrium sp. S31 (Chang, Luo, Gu, Wu, & Wang, 2013).…”

Effect ofN-Propyl Gallate on Lipid Peroxidation in Heterogenous Model Membranes

“…As highlighted above, nPG is recognized as a powerful antioxidant and added to foods (especially oils and fats), cosmetics and hair products (8). Besides its antioxidant activity, nPG displays pharmacological effects such as anti-inflamatory (11) and anti-tumor activities (20).…”

“…its radical scavenging effect is due to gallic acid (3,4,5-trihydroxybenzoic acid), which is a natural component of many plants (2,8). nPG as well as other synthetic derivatives of the galic acid are commonly used as antioxidants in the food industry (28,29,35).…”