The potential antifibrotic impact of apocynin and alpha-lipoic acid in concanavalin A-induced liver fibrosis in rats: Role of NADPH oxidases 1 and 4

Background: Sodium valproate (VPA) is an antiepileptic drug (AED) licensed for epilepsy and used during pregnancy in various indications. Alpha-lipoic acid (ALA) is a natural compound inducing endogenous antioxidant production. Our study aimed to investigate the effect of prenatal administration of VPA on the pancreas of rat offspring and assess the potential protective role of ALA co-administration during pregnancy. Methods: Twenty-eight pregnant female albino rats were divided into four groups: group I (negative control), group II (positive control, ALA treated), group III (VPA-treated), and group IV (VPA-ALA-treated). The pancreases of the rat offspring were removed at the fourth week postpartum and prepared for histological, immune-histochemical, morphometric, molecular, and oxidative stress marker studies. Results: In group III, there were pyknotic nuclei, vacuolated cytoplasm with ballooning of acinar, α, and β cells of the pancreas. Ultrastructural degeneration of cytoplasmic organelles was detected. Additionally, there was a significant increase in oxidative stress, a decrease in insulin-positive cell percentage, and an increase in glucagon positive cells in comparison to control groups. Moreover, VPA increased the gene expression of an apoptotic marker, caspase-3, with a decrease in anti-apoptotic Bcl2 and nuclear factor erythroid 2-related factor 2 (Nrf2) transcriptional factor. Conversely, ALA improved oxidative stress and apoptosis in group VI, and a consequent improvement of the histological and ultrastructure picture was detected. Conclusion: ALA co-administration with VPA significantly improved the oxidative stress condition, histological and morphometric picture of the pancreas, and restored normal expression of related genes, including Nrf2, caspase-3, and Bcl-2. Administration of α-lipoic acid has a protective effect against VPA-induced pancreatic oxidative damage via its cytoprotective antioxidant effect.

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PSXIV-19 Effect of alpha-lipoic acid on productive parameters and ruminal VFA profile in sheep

Journal of Animal Science ◽

10.1093/jas/skz258.866 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 437-438

Author(s):

Carolina Robles ◽

Laura Gonzáles Davalos ◽

Ofelia Mora ◽

Yesmin Hermanadez ◽

Armando Shimada ◽

...

Keyword(s):

Blood Glucose ◽

Lipoic Acid ◽

Insulin Receptors ◽

Daily Weight Gain ◽

Oxidative Decarboxylation ◽

Alpha Lipoic Acid ◽

Randomized Design ◽

Keto Acids ◽

Mechanism Research

Abstract Alpha lipoic acid (LA) is a potent nutritional antioxidant. It is a derivate of octanoic acid containing a cyclic disulfide bond. An LA complex with lysine-lipoamide, functions as a co-factor in the mitochondrial dehydrogenase that catalyzes the oxidative decarboxylation of α-keto acids. In this reaction, LA is reduced to dihydrolipoic acid (DHLA), which interacts with reactive oxygen species, and LA can also inactivate free radicals. Another important role of DHLA is in signal transduction by activating insulin receptors, which causes glucose transporters translocation from cytoplasm to the cell surface. Due to its potential antioxidant effect at ruminal level, the aim of this study was to evaluate the effect of fed LA on productive parameters, ruminal fatty volatile fatty acid (VFA) concentration and blood glucose of sheep. Sixty-four, two-months-old, crossbred lambs were penned in groups of four, divided into four treatments: 0, 40, 80, and 120 ppm LA in diet. During 84 days, every 28 days on two consecutive days, animals were weighed (to determine average daily weight gain, DWG), blood and ruminal fluid were taken for glucose and VFA quantification, respectively. All variables were analyzed in a completely randomized design. DWG was statistically higher in those animals receiving 80 ppm (250 g) as compared to the rest (200, 188, 180 g for 120, 40, 0 ppm, respectively) (P < 0.0001). No differences in blood glucose or ruminal VFA were found (P > 0.1). LA could improve the productive performance of sheep; however, it would be necessary to study the role of LA and its effects on the ruminal microbiome and its action mechanism. Research support by Project PAPIIT-UNAM IN211518

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