Evaluation of lipoic acid topical application on rats skin wound healing

PURPOSE: To evaluate the effects of lipoic acid (thioctic acid) topical application on wound healing on rats skin, and the consequences of lipoic acid nanoencapsulation on this process. METHODS: The model used was the healing activity on wounds induced by surgical incision on rats skin (n = 44). The parameters analyzed (11 days) were wound healing rate and histology (vascular proliferation, polymorphonuclear or mononuclear cells, and collagen synthesis or reepithelialization), after application of free lipoic acid or lipoic acid- loaded nanocapsules. The antioxidant activity of these formulations was evaluated by lipid peroxidation test. RESULTS: It was demonstrated for the first time that the topical application of lipoic acid improves wound healing. On the seventh day after surgery, the animals treated with lipoic acid showed increased healing rate (60.7 ± 8.4%) compared to the negative control group (43.0 ± 17.4%), as so improvement of histological parameters. The nanoencapsulation reverted the pro-oxidant activity presented in vitro by lipoic acid, whereas diminished wound repair. CONCLUSIONS: The topical application of lipoic acid produced an increase in the skin wound healing, which may be related to its pro-oxidant activity. On the other hand, the nanoencapsulation of the lipoic acid reversed the pro-oxidant activity, although presented minor healing activity.

Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients

To examine the effects of alpha-lipoic acid [ALA] treatment over a period of 2 months on fasting blood glucose [FBG], insulin resistance [IR], and glutathione peroxidase [GH-Px] activity in type 2 diabetes [T2DM] patients. This study took place in Motahari Clinic, Shiraz, Iran, which is affiliated to Shiraz University of Medical Sciences from May to October 2006. Type 2 DM patients [n=57] were divided into 2 groups to receive either ALA [300 mg daily] or placebo by systematic randomization, and were followed-up for 8 weeks. After an overnight fasting and 2 hours after breakfast, patients' blood samples were drawn and tested for FBG, 2 hours PPG, serum insulin level, and GH-Px activity. The result of the study showed a significant decrease in FBG and PPG levels, IR-Homeostasis Model Assessment [IR-HOMA index] and GH-Px level in the ALA group. The comparison of differences between FBG and IR at the beginning and at the end of study in the ALA treated group and the placebo group were also significant. This study supports the use of ALA as an antioxidant in the care of diabetic patients

Lipoic acid restores antioxidant system in tissues of hyperinsulinaemic rats.

BACKGROUND & OBJECTIVES: Feeding rats with high fructose induces insulin resistance, hyperinsulinaemia, elevation of blood glucose level and impaired glucose tolerance. Oxidative stress plays a vital role in pathology associated with insulin resistance. The present study was to investigate the effects of alpha-lipoic acid (LA) on the oxidant-antioxidant balance in liver and kidney of high fructose-fed rats. METHODS: Male Wistar rats (170-180 g) were divided into six groups. The control group received diet containing starch; the fructose group was given a high fructose diet (>60% of total calories); the third and fourth groups were given fructose diet and administered with two different doses of lipoic acid as low dose (35 mg/kg body weight) and high dose (70 mg/kg bw) intraperitoneally using olive oil as vehicle; the fifth group received control diet and was administered with lipoic acid (70 mg/kg bw); the sixth group received the control diet and olive oil. The rats were maintained in their respective dietary regimen for 20 days. Lipid peroxidation indices and antioxidant status in liver and kidney were quantitated. RESULTS: The rats fed fructose showed increased levels of lipid hydroperoxides, thiobarbituric acid reactive substances (TBARS), conjugated dienes, and impaired antioxidant defence potential as evidenced by a decrease in the levels of non-enzymatic and enzymatic antioxidants. Treatment with LA to the fructose-fed rats mitigated these alterations and LA was effective uniformly at both the closes. Increased lipid peroxidation and inadequate antioxidant system are observed in the high dose fructose-fed rats. INTERPRETATION & CONCLUSION: LA administration restored the antioxidant potential and lowered lipid peroxidation. These findings strengthen the utility of LA in the management of insulin resistance and associated pathology.

Efeito da metformina e do ácido lipóico nas reservas de glicogênio de músculos denervados e de ratos diabéticos / The effect of metformin and lipoic acid on glycogen reserves of denervated and diabetic rat muscles

As açöes da insulina ocorrem após sua ligaçäo ao receptor e conseqüente ativaçäo de seus substratos citoplasmáticos. Tecidos de indivíduos resistentes à insulina, incluindo adipócitos, músculo e fígado mostraram diminuiçäo na atividade do receptor, enquanto estudos realizados com tecidos de pacientes com diabetes mellitus, näo dependentes de insulina, mostraram diminuiçäo na açäo da insulina, quando comparados com indivíduos normais. Muitos trabalhos sugerem que concentraçöes terapêuticas de metformina (MET) estimulam a atividade de substratos ligados aos receptores de insulina. Recentes estudos têm sugerido que o ácido tióctico (TA), substância antioxidante, usada no tratamento do diabetes, também exerce efeito periférico, melhorando o transporte e metabolismo da glicose. No presente estudo, foi avaliado o efeito metabólico do ácido tióctico (0,1 mg.ml-û) em estados de resistência à insulina, induzido pelo diabetes ou denervaçäo muscular. Observou-se que a denervaçäo e o diabetes promoveram a reduçäo no conteúdo muscular de glicogênio (GLY), atingindo 60 por cento no sóleo e 40 por cento no gastrocnêmio. A MET induziu elevaçäo nas reservas de GLY dos músculos normais, atingindo 297 por cento no sóleo e 393 por cento no gastrocnêmio. Foi observada, nos músculos de ratos diabéticos, reduçäo no GLY, atingindo 50 por cento no sóleo e 24 por cento no gastrocnêmio. Por sua vez, MET e TA induziram elevaçäo no conteúdo de GLY nos músculos de ratos diabéticos, atingindo 84 por cento no sóleo e 44 por cento no gastrocnêmio e 573 por cento no sóleo e 296 por cento no gastrocnêmio, respectivamente. No entanto, o tratamento com TA näo apresentou efeito significativo sobre o conteúdo muscular de GLY de ratos normais ou denervados. Este estudo mostra que, nos músculos denervados, o tratamento com MET restabeleceu a capacidade de sintetizar glicogênio, apontando para a melhora no metabolismo das fibras. Por outro lado, nos músculos denervados, o tratamento com TA näo promoveu efeito benéfico. Estes dados mostram que o estado de resistência à insulina, observado no diabetes, difere do estado de resistência observado nos músculos denervados.

Inactivation of Trypanosoma cruzi dihydrolipoamide dehydrogenase by leukocyte myeloperoxidase systems: role of hypochloride and nitrite related radicals

Dihydrolipoamide dehydrogenase (LADH) from Trypanosoma cruzi, the causative agent of Chagas' disease, was inactivated by treatment with myeloperoxidase (MPO)-dependent systems. LADH lipoamide reductase and diaphorase activities decreased as a function of incubation time and composition of the MPO/H2O2/halide system, a transient increase preceding the loss of diaphorase activity. Iodide, bromide, thiocyanide and chloride were effective components of MPO/H2O2 or MPO/NADH systems. Catalase prevented LADH inactivation by the MPO/NADH/halide systems in agreement with H2O2 production by NADH-supplemented LADH. Thiol compounds (L-cysteine, N-acetylcysteine, penicillamine, N-(2-mercaptopropionylglycine) and Captopril prevented LADH inactivation by the MPO/H2O2/NaCl system and by NaOCl, thus supporting HOCl as agent of the MPO/H2O2/NaCl system. MPO/H2O2/NaNO2 and MPO/NADH/NaNO2 inactivated LADH, the reaction being prevented by MPO inhibitors and thiol compounds. T. cruzi LADH was affected by MPO-dependent systems like myocardial LADH, allowance being made for the variation of the diaphorase activity and the greater sensitivity of the T. cruzi enzyme to MPO/H2O2/halide systems.