Alpha-Lipoic Acid Prevents Endotoxic Shock and Multiple Organ Dysfunction Syndrome Induced by Endotoxemia in Rats

Abstract

Alpha-lipoic acid (ALA), a naturally occurring disulfide derivative of octanoic acid, serves as a strong antioxidant and has been reported to possess anti-inflammatory effects. The aim of the present study is to investigate the preventive and therapeutic effects of ALA on multiple organ dysfunction syndrome (MODS) caused by endotoxemia in rats. Male Wistar rats were intravenously infused with lipopolysaccharide (LPS) (10 mg/kg) to induce endotoxemia. Alpha-lipoic acid 10, 20, or 40 mg/kg was administered intravenously 60 min before (pretreatment) LPS challenge, and ALA 40 mg/kg was administered intravenously 30 min after (posttreatment) LPS challenge. Pretreatment and posttreatment with ALA significantly improved the deleterious hemodynamic changes 8 h after LPS challenge, including hypotension and bradycardia. Alpha-lipoic acid reduced the plasma levels of glutamic pyruvic transaminase, blood urea nitrogen, lactate dehydrogenase, tumor necrosis factor-α, nitric oxide metabolites, and thrombin-antithrombin complex, which increased markedly after LPS challenge. The induction of inducible nitric oxide synthase both in the liver and the lung and vascular superoxide anion production were also significantly suppressed by ALA. Moreover, ALA significantly attenuated LPS-induced caspase-3 activation in cardiomyocytes and improved survival rate. In conclusion, ALA effectively attenuated LPS-induced acute inflammatory response and improved MODS. The antioxidant and anti-inflammatory effects of ALA may contribute to these beneficial effects. Alpha-lipoic acid might be considered as a novel therapeutic strategy in the prevention of sepsis-induced MODS and inflammatory vascular diseases.

Protective Effects of Antioxidant Peptide SS-31 Against Multiple Organ Dysfunctions During Endotoxemia

“…Consistently, antioxidants have been demonstrated to attenuate mortality or prevent organ dysfunctions in endotoxemic animal models and are helpful in protecting against MODS in patients with septic shock [4][5][6]. During endotoxemia, the inflammatory cells have the potential to produce large amounts of ROS and RNS by various mechanisms [5,6], which in turn can lead to amplified inflammatory responses. Oxidative stress induces peroxidation of membrane lipids, affecting the biological properties of the cellular membrane and impairing normal cellular function [5,6].…”

“…The burst of ROS can trigger the opening of the mitochondrial permeability transition pore, resulting in mitochondrial depolarization, decreased ATP synthesis, and increased ROS production [9]. Consistently, antioxidants have been demonstrated to attenuate mortality or prevent organ dysfunctions in endotoxemic animal models and are helpful in protecting against MODS in patients with septic shock [4][5][6]. During endotoxemia, the inflammatory cells have the potential to produce large amounts of ROS and RNS by various mechanisms [5,6], which in turn can lead to amplified inflammatory responses.…”

“…Sepsis represents an exaggerated inflammatory response and oxidative stress to infection that can progress to multiorgan dysfunction syndromes (MODS), which is characterized by a massive deregulated inflammatory response, overproduction of reactive oxygen species (ROS), and reactive nitrogen species (RNS) in the circulation and the affected organs [4][5][6]. However, current therapeutic options for sepsis-associated organ dysfunctions are limited, thus the development of new drug is urgently needed.…”

Effect of -Lipoic Acid on Proteasomal Induction: Protection against Oxidative Damage in Human Skin Fibroblasts Cell Line NHDF

“…Here, we elucidated a third mechanism for the antioxidant capacity of LA in skin cells, which is the stimulation of inner detoxification mechanisms in order to eliminate unwanted oxidative products. Although it has been previously described in IPEC-J2 cell lines [1] that LA shows pre-protective effects towards oxidative stress, our study brings a whole new approach of the prophylactic potential of LA against human skin aging through the induction of the 20S proteasome leading to the decrease of oxidative damage.…”

“…Also called "the universal antioxidant", lipoic acid is a disulfide derivative of octanoic acid produced by human body [1]. Currently, it is attracting attention as a nutritional supplement because of its unique antioxidant properties and broad spectra of cellular functions.…”