Alpha-lipoic acid treatment ameliorates metabolic parameters, blood pressure, vascular reactivity and morphology of vessels already damaged by streptozotocin-diabetes.
The present study investigated the effects of alpha-lipoic acid treatment (50 mg/kg/day) on the metabolism and vascular condition already damaged by streptozotocin (STZ)-diabetes in rats. Carbohydrate and lipid metabolism, oxidative stress and antioxidant status were assessed in non-diabetic controls, 12-week untreated diabetic and 12-week treated diabetic (untreated for 6 weeks and then treated with alpha-lipoic acid for the last 6 weeks) rats. Blood pressures of rats were measured by tail-cuff method. Vascular reactivity was evaluated in isolated aortic rings. Morphology of aorta was examined by electron microscopy technique. Alpha-lipoic acid treatment effectively reversed body weight, blood glucose, plasma insulin, cholesterol, triglycerides and lipid peroxidation levels of diabetic animals. STZ-diabetes resulted in increased blood pressure, which was partially improved by alpha-lipoic acid treatment. Although the superoxide dismutase (SOD) activity in aortic homogenates was not changed by diabetes or antioxidant treatment, catalase or glutathione peroxidase (GPx) activity significantly increased in untreated diabetic rats. Alpha-lipoic acid treatment improved catalase activity in diabetic aorta. The contractile effect of phenylephrine markedly increased in diabetic rings, which was completely reversed by alpha-lipoic acid treatment. The maximum vasorelaxant response of pre-contracted aortic rings exposed to cumulatively increased concentrations of acetylcholine was unaffected by diabetes or antioxidant treatment. Sodium nitroprusside-induced endothelium-independent relaxations were similar in all experimental groups. Various alterations caused by STZ-diabetes in aorta structure were partially ameliorated by alpha-lipoic acid treatment. The potency of alpha-lipoic acid on the reversal of hypertension by affecting vascular reactivity and morphology as well as general metabolism of diabetic rats confirms the importance of hyperglycemia-induced oxidative stress in the development of diabetes-induced vascular complications and suggests a potential therapeutic approach.
Koçak G
，Aktan F
，Canbolat O
，Ozoğul C
，Elbeğ S
，Yildizoglu-Ari N
，Karasu C
，ADIC Study Group--Antioxidants in Diabetes-Induced Complications
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《diabetes nutrition & metabolism》
Effects of alpha lipoic acid, ascorbic acid-6-palmitate, and fish oil on the glutathione, malonaldehyde, and fatty acids levels in erythrocytes of streptozotocin induced diabetic male rats.
In this research, it has been aimed to evaluate the improvement effects of alpha lipoic acid (ALA), ascorbic acid-6-palmitate (AA6P), fish oil (FO), and their combination (COM) on some biochemical properties in erythrocytes of streptozotocin (STZ)-induced diabetic male rats. According to experimental results, glutathione (GSH) level in erythrocytes decreased in diabetes (P < 0.01), D + ALA, and D + AA6P groups (P < 0.001). Malonaldehyde (MA) level increased in diabetes (P < 0.05), D + FO, and D + COM groups (P < 0.001), but its level in D + AA6P and D + ALA groups was lower in diabetes group (P < 0.01). Total lipid level in diabetes and diabetes plus antioxidant administered groups were higher than control. Total cholesterol level was high in diabetes and D + ALA groups (P < 0.05), but its level reduced in D + FO compared to control and diabetes groups, P < 0.05, < 0.001, respectively. Total triglyceride (TTG) level was high in the D + ALA (P < 0.05) and D + COM (P < 0.001) groups. In contrast, TTG level in blood of diabetes group was higher than diabetes plus antioxidant and FO administered groups (P < 0.001). According to gas chromatography analysis results, while the palmitic acid raised in diabetes group (P < 0.05), stearic acid in D + FO, D + ALA, and diabetes groups was lower than control (P < 0.05), oleic acid reduced in D + COM and D + FO groups, but its level raised in D + AA6P and D + ALA groups (P < 0.01). As the linoleic acid (LA) elevated in ALA + D, D + AA6P, and diabetes groups, linolenic acid level in diabetes, D + AA6P, and D + FO groups was lower than control (P < 0.001). Arachidonic acid (AA) decreased in D + ALA, D+ AA6P, and diabetes groups (P < 0.01), but its level in D + COM and D + FO was higher than control (P < 0.05). Docosahexaenoic acid (DHA) increased in D + AA6P and D + COM (P < 0.05). While the total saturated fatty acid level raised in diabetes group, its level reduced in D + ALA and D + FO groups (P < 0.05). In contrast, total unsaturated fatty acid level in D + ALA and D + FO groups was higher than control (P < 0.05). In conclusion, present data have confirmed that the combination of the ALA, AA6P, and FO have improvement effects on the recycling of GSSG to reduced GSH in erythrocytes of diabetic rats, and in addition to this, oxidative stress was suppressed by ALA and AA6P, and unsaturated fatty acid degree was raised by the effects of ALA and FO.
Yilmaz O
，Ozkan Y
，Yildirim M
，Oztürk AI
，Erşan Y
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《JOURNAL OF CELLULAR BIOCHEMISTRY》
Alpha-lipoic acid treatment prevents the diabetes-induced attenuation of the afferent limb of the baroreceptor reflex in rats.
Autonomic neuropathies, common complications of prolonged diabetes, may result from diabetes-induced increased oxidative stress. Recently, we found that the afferent component of the baroreceptor reflex is attenuated in streptozotocin-induced diabetic rats. This study sought to determine the influence of the anti-oxidant, alpha-lipoic acid on the diabetes-induced deficits of the afferent limb of the baroreceptor reflex and on plasma malondialdehyde (a measure of lipid peroxidation). The number of c-Fos-ir neurons in the nucleus tractus solitarius in response to phenylephrine-induced baroreceptor activation was used as an index of the integrity of the afferent limb of the baroreceptor reflex. Groups of streptozotocin-induced diabetic and non-diabetic control rats, maintained from 8 to 16 weeks, were treated with alpha-lipoic acid (100 mg kg(-1) IP, 5x/week), or vehicle for the last 4 weeks prior to the experimental procedure. Vehicle-treated diabetic rats had elevated plasma malondialdehyde levels when compared to non-diabetic rats. alpha-Lipoic acid-treated diabetic rats had plasma malondialdehyde levels similar to those seen in non-diabetic rats and less than those of vehicle-treated diabetic rats at both the 8- and 16-week time points.alpha-Lipoic acid treatment did not affect the baseline (absence of baroreceptor activation) presence of c-Fos-ir in the nucleus tractus solitarius. In response to phenylephrine and regardless of treatment, the diabetic and control rats displayed increases in blood pressure and reflex bradycardia. As previously reported, phenylephrine-induced baroreceptor activation resulted in significantly fewer c-Fos-ir neurons in the nucleus tractus solitarius (commissural and caudal subpostremal regions) of diabetic rats when compared to non-diabetic rats at both 8- and 16-week time points. Four weeks of alpha-lipoic acid treatment reversed the diabetes-induced decrement in the numbers of c-Fos-ir neurons in the nucleus tractus solitarius in response to baroreceptor activation. alpha-Lipoic acid-treated diabetic rats showed the same phenylephrine-induced c-Fos response in the nucleus tractus solitarius as those of alpha-lipoic-acid- and vehicle-treated control rats at both 8- and 16-week time points. These data suggest that diabetes-induced oxidative stress plays a role in diabetes-induced baroreceptor dysfunction and that the alpha-lipoic acid may have a beneficial effect in treatment of diabetic autonomic neuropathy.
Gouty S
，Regalia J
，Cai F
，Helke CJ
... -
《AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL》
The effect of alpha-lipoic acid on NOS dispersion in the lung of streptozotocin-induced diabetic rats.
Oxidative stress and impaired bioactivity of nitric oxide (NO) play an important role in the organ pathogenesis and angiopathic complications of diabetes mellitus. In this study, we evaluated the effects of alpha-lipoic acid (ALA) on nitric oxide synthase (NOS) in lung tissues. ALA is a strong antioxidant. We wonder how it can affect oxidative stress and NO in the lung cells and vessels of diabetic rats. Wistar rats were divided into four groups; control, diabetic [65 mg/kg streptozotocin (STZ) for 15 days], STZ+ALA-treated (65 mg/kg ALA every 2 days for 15 days), and ALA-only-treated animals. At the end of the experimental period, lipid peroxidation, superoxide dismutase (SOD), and inducible NOS (iNOS) and endothelial NOS (eNOS) distribution were evaluated. Oxidative stress decreased with ALA in diabetic animals, and SOD also increased with ALA. iNOS and eNOS increased in diabetic animals, and ALA prevented iNOS increment in lung tissues. As a result, ALA can prevent some diabetic effects on the lungs and can also protect from vascular damages.
Hürdağ C
，Uyaner I
，Gürel E
，Utkusavas A
，Atukeren P
，Demirci C
... -
《JOURNAL OF DIABETES AND ITS COMPLICATIONS》
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