Impact of Alpha-Lipoic Acid Chronic Discontinuous Treatment in Cardiometabolic Disorders and Oxidative Stress Induced by Fructose Intake in Rats

Abstract

Insulin resistance (IR) and cardiometabolic disorders are the main consequences of today's alimentary behavior. This study evaluates the effects of a chronic-discontinuous treatment with alpha-lipoic acid (AL), an antioxidant substance that improves glycemic control associated with diabetes mellitus, on metabolic disorders and plasma oxidative stress induced by fructose intake, in rats. Sprague-Dawley rats (48 animals) were randomized into two series (n = 24): rats fed with standard chow or with standard chow supplemented with 60% fructose. In each of the two series, for 2 weeks/month over 12 weeks, a group of rats (n = 12) was intraperitoneally injected with NaCl 0.9%, and a second group (n = 12) received AL 50 mg/kg/day. Body weight, glycemia, and systolic blood pressure were monitored throughout the study. After 12 weeks, IR, plasma lipoproteins, uric acid, transaminase activities, and oxidative stress markers were assessed. The high fructose-enriched diet induced cardiometabolic disorders (hypertension, hyperglycemia, IR and dyslipidemia), an increase in uric acid concentration, transaminase activities and C-reactive protein level. This diet also enhanced plasma products of lipid and protein oxidation, homocysteine level, and decreased GSH/GSSG ratio. In this field, there is evidence to indicate that oxidative stress plays an important role in the etiology of diabetic complications. AL discontinuous treatment prevents the metabolic disorders induced by fructose intake, reduced plasma lipid and protein oxidation-products, and restored the GHS/GSSG ratio. Our study proves a promising potential of the chronic-discontinuous treatment of AL and highlights the pleiotropic effects of this antioxidant substance in metabolic disorders such as diabetes.

An Exploratory Research of 18 Years on the Economic Burden of Diabetes for the Romanian National Health Insurance System

“…The DM leads to a diminution of life quality due to both acute and chronic consequences, reduces life expectancy and leads to higher mortality [3][4][5][6]. DM caused 4.0 million deaths in 2017.…”

Protective Effects of a Discontinuous Treatment with Alpha-Lipoic Acid in Obesity-Related Heart Failure with Preserved Ejection Fraction, in Rats

“…Because obesity is difficult to assess in animals, abdominal fat accumulation can confirm the obesity status [42], which was also reported in our study. Additionally, the presence of fructose in the diet inhibits fatty acids oxidation and amplifies hypertriglyceridemia, peripheral insulin resistance and visceral adiposity [17,42,49,50]. Although a hypercaloric diet generates carbohydrate and lipid metabolism disruptions and systolic blood pressure increase, Vileigas et al show that cardiac function impairment appears only in the western diet with higher fat predominance (high fat western diet) [47], emphasizing the effect of diet composition on cardiac risk.…”

“…Additionally, metabolic and cardiovascular disorders associated with obesity are characterized by significant increases in ROS production and the breakdown of endogenous antioxidant systems. This creates a vicious circle which amplifies the pre-existing disturbances [17][18][19][20][21].…”

“…Moreover, its safety profile is well characterized [23] and its specific amphiphilic properties could allow for a better intra-cellular and extra-cellular distribution [22]. Consequently, multiple studies have reported the benefits of ALA treatment in metabolic syndrome (hyperglycemia, tissue insulin resistance and dyslipidemia) [17], hypertension [17,24] and obesity [25][26][27].…”

Oxidative Stress and Obesity- and Type 2 Diabetes-Induced Heart Failure

“…In their study, Kar et al [12] show that this beneficial effect is related to a change in the antioxidant hydrogen sulfide in the heart and a modulation of pyroptosis. A second study [13] describes the effects of the antioxidant alpha-lipoic acid given as chronic discontinuous treatment on several markers of insulin resistance, plasma oxidative stress and inflammation. The investigators reveal that the type of treatment given has beneficial actions on several of the studied parameters.…”