Adverse cardiac responses to alpha-lipoic acid in a rat-diabetic model: possible mechanisms?

Abstract

Alpha-lipoic acid (ALA) is widely used as an antioxidant for the treatment of diabetes and its complications; however, the pro-oxidant potential of ALA has recently been reported. This study was designed to investigate whether ALA supplementation could have pro-oxidant effects on cardiac tissues in normal and diabetic rats. Diabetes was induced by a single dose of streptozotocin (STZ; 55 mg/kg (intraperitoneal). Diabetic and normal rats were treated with ALA (100 mg kg(-1) day(-1)) for 45 days. ALA supplementation resulted in oxidative protein damage as evident by significant reduction in the cardiac levels of protein thiol in ALA-treated normal rats (P < 0.01) together with a significant elevation (P < 0.001) in the plasma levels of advanced oxidation protein products in ALA-treated normal rats and in ALA + STZ-diabetic rats compared with the normal control rats. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has emerged as the major source of superoxide anion and enhanced oxidative damage in heart failure. ALA supplementation increased the myocardial immunoreactivity of p47phox subunit of NADPH oxidase in both normal nondiabetic and diabetic rats reflecting its pro-oxidant effect. Data showed that ALA supplementation failed to prevent cardiac complications in diabetic rats and led to cardiac toxicity in normal rats as indicated by pathological changes (cellular infiltration, fibrosis, and degeneration) and by the elevation of serum cardiac biomarkers compared with normal controls. The pro-oxidant effects of ALA suggest that careful selection of appropriate doses of ALA in reactive oxygen species-related diseases are critical.

Possible Regulatory Effects of Application of Alpha Lipoic Acid and Insulin Against Cadmium Exposed Diabetic Rats

“…On the other hand, there is connection with Cd exposure and diabetes as previous reports (4). Some research has demonstrated that the application of exogenous antioxidants can be supportive therapy to treat diabetes in mammals (11). In light of the above insight, the object of our study was to explore the potential influence of insulin and LA which is an antioxidant that has been clinically tested as a treatment for diabetes, against the Cd exposure in type I diabetic rats.…”

“…Lipoic acid (LA), or 1,2-dithiolane-3-pentanoic acid, is a naturally consisting dithiol substance, essential for the functions as a cofactor for some mitochondrial enzymes, cause the manufacture of ATP. It is known that LA has strong antioxidant potency and is influential in both oxidative stress inhibition and management in a number of models or clinical conditions, including diabetes (11). LA is a powerful compound with amphipathic properties, is capable of extinguishing free radical, chelating metal and regenerating other antioxidants (6).…”

Possible protective mechanisms exerted by metformin or metformin and vitamin E in isoproterenol‐induced cardiac injury

“…A mixture of 250 µL of heart homogenate, 1.25 mL Trichloroacetic acid solution, and 0.5 mL thiobarbituric acid solution was heated for 30 min in a boiling water bath, cooled and centrifuged at 4°C, 3000 rpm for 10 min. The absorbance was measured at 535 nm against a reagent blank …”

Alpha-Lipoic Acid Prevents Atrial Electrical and Structural Remodeling via Inhibition of NADPH Oxidase in a Rabbit Rapid Atrial Pacing Model

“…Tissue processing [30] The hearts were excised and washed immediately with buffered saline (pH 7.4) to remove any red blood cells and clots. The tissues were then weighed and homogenized in normal saline (0.9%) for 2 min.…”

“…Histopathological analysis [30] Samples of heart tissues were washed immediately with saline (0.9%) and xed in 10% phosphate buffered formalin solution for 24 h. The tissues were then dehydrated in ascending grades of ethyl alcohol, cleared with xylene, and embedded in para n. Para n blocks were cut by a microtone to prepare 5 µm thick sections. Sections were stained with hematoxylin-eosin (H&E) to stain the nucleus and cytoplasm and with Masson's trichome to stain collagen bers for the detection of brosis.…”