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Tetradecylthioacetic acid (TTA) is a novel thio-fatty acid which cannot undergo beta-oxidation. It induces apoptosis in IPC-81 leukemia cells via depolarization of mitochondrial membrane potential and inhibits glioma cell proliferation. TTA completely prevents high-fat diet induced insulin resistance and adiposity in Wistar rats. Activates rodent PPARs with rank order PPAR α > PPAR Δ > PPAR γ.
Tetradecylthioacetic acid (TTA) which can not be β-oxidized, lowers plasma VLDL-triacylglycerol (TG) and LDL-cholesterol (Chol). Increased mitochondrial β-oxidation with a concomitant decrease in TG synthesis and secretion, seems to be the primary mechanism underlying the hypotriglyceridemic effect not only of TTA but also of w-3 fatty acids as well as fibrates in rats, rabbits, dogs and possibly also in humans. TTA is an inhibitor of HMG-CoA reductase. We have generated results both in vivo and in vitro that present evidence that TTA besides being a lipid-lowering agent, also possesses antioxidant properties. First, TTA inhibits the oxidative modification of LDL, which is considered as the key step in the formation of foam cells and in initiation and progression of atherosclerotic plaque.
Also TTA changes the antioxidant defense system in a beneficial way i.e. glutathion (GSH) is increased, the total antioxidant status is elevated and TBARS are decreased. Second, TTA has an alive oil-effect since the plasma was enriched with oleic acid (18:1 n-9) and a 2-desaturated metabolite of TTA. This was due to upregulation of the hepatic enzyme 2-desaturase gene expression. Third, TTA lowers the plasma homocysteine level and inhibits restenosis. Fourth, TTA reduces the proliferation of smooth muscle cells. In conclusion, TTA is a hypolipidemic drug but also a new antioxidant. This novel bioactive compound is promising as a new therapeutic drug against atherosclerosis as it changes the plasma profile from atherogenic to cardioprotective.
Tetradecylthioacetic acid (TTA) which can not be β-oxidized, lowers plasma VLDL-triacylglycerol (TG) and LDL-cholesterol (Chol). Increased mitochondrial β-oxidation with a concomitant decrease in TG synthesis and secretion, seems to be the primary mechanism underlying the hypotriglyceridemic effect not only of TTA but also of w-3 fatty acids as well as fibrates in rats, rabbits, dogs and possibly also in humans. TTA is an inhibitor of HMG-CoA reductase. We have generated results both in vivo and in vitro that present evidence that TTA besides being a lipid-lowering agent, also possesses antioxidant properties. First, TTA inhibits the oxidative modification of LDL, which is considered as the key step in the formation of foam cells and in initiation and progression of atherosclerotic plaque.
Also TTA changes the antioxidant defense system in a beneficial way i.e. glutathion (GSH) is increased, the total antioxidant status is elevated and TBARS are decreased. Second, TTA has an alive oil-effect since the plasma was enriched with oleic acid (18:1 n-9) and a 2-desaturated metabolite of TTA. This was due to upregulation of the hepatic enzyme 2-desaturase gene expression. Third, TTA lowers the plasma homocysteine level and inhibits restenosis. Fourth, TTA reduces the proliferation of smooth muscle cells. In conclusion, TTA is a hypolipidemic drug but also a new antioxidant. This novel bioactive compound is promising as a new therapeutic drug against atherosclerosis as it changes the plasma profile from atherogenic to cardioprotective.