Alpha-Lipoic Acid Exerts Anti-Inflammatory Effects on Lipopolysaccharide-Stimulated Rat Mesangial Cells via Inhibition of Nuclear Factor Kappa B (NF-κB) Signaling Pathway

Abstract

Sepsis is often initiated by invasive infection, characterized by overwhelming induction of pro-inflammatory cytokines. The incidence and mortality of sepsis and the associated development of acute kidney injury (AKI) remain high, and lines of research into potential treatments are needed. This study was conducted to investigate effects of alpha-lipoic acid (ALA) on septic AKI in vitro. ALA of 200 or 400 μM was used to pretreat rat HBZY-1 mesangial cells before commencement of 1 μg/mL lipopolysaccharide (LPS). Our data indicated that ALA pretreatment reduced LPS-stimulated release of inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1 beta (IL-1β), as well as IL-6, in HBZY-1 cell supernatant. Moreover, LPS-induced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was inhibited by ALA pretreatment, and consequently, the secretion levels of their respective enzymatic products prostaglandin E2 (PGE2) and nitric oxide (NO) were significantly decreased. LPS-enhanced phosphorylation of nuclear factor kappa B (NF-κB) inhibitor alpha (IκBα) and IκB kinase alpha/beta (IKKα/β) and nuclear translocation of NF-κB subunit p65 in HBZY-1 cells were inhibited by ALA pretreatment. Additionally, the NF-κB inhibitor N-acetylcysteine (NAC) exerted similar inhibitory effects as ALA on COX-2 and iNOS expression. In summary, our study demonstrates that ALA mitigates LPS-induced inflammatory responses in rat mesangial cells probably via inhibition of NF-κB signaling pathway, suggesting a therapeutic potential of ALA in AKI related to sepsis.

Alpha-Lipoic Acid Suppresses Extracellular Histone-Induced Release of the Infammatory Mediator Tumor Necrosis Factor-α by Macrophages

“…We confirmed that extracellular histone-induced TNF-α release was mediated via the MAPK and NF-κB pathways and that ALA can significantly reduce TNF-α release in parallel with the suppression of the MAPK and NF-κB pathways. These effects on the phosphorylation (activation) of ERK, p38, and NF-κB p65 are consistent with previous studies in human aortic endothelial cells [44] and LPS-stimulated rat mesangial cells [36]. Notably, ALA reduced this pro-inflammatory response at doses that did not markedly affect cell viability.…”

“…Zhang et al found that ALA reduces lipopolysaccharide (LPS)-induced inflammatory responses in human monocytes by activating the PI3K/AKT signaling pathway [35]. Moreover, ALA prolongs survival and attenuates inflammatory responses in a rat model of sepsis by blocking the activation of the NF-κB pathway [36]. However, the signaling pathways via which extracellular histones mediate inflammation and those underlying the anti-inflammatory effects of ALA are unclear.…”

A carvacrol–thymol blend decreased intestinal oxidative stress and influenced selected microbes without changing the messenger RNA levels of tight junction proteins in jejunal mucosa of weaning piglets

“…Among the ingredients in the antioxidant blend used in that study, both tea polyphenols and lipoic acid exert antiinflammatory effects via inhibition of the nuclear factor-κB (NF-κB) signaling pathway (Goraca et al, 2015;Li et al, 2015;Marinovic et al, 2015). Therefore, the antioxidant blend used in that study might also have reduced weaning-induced intestinal inflammation effectively.…”

Immunomodulatory activities of alpha lipoic acid with a special focus on its efficacy in preventing miscarriage

“…A similar decrease was detected in the secretion levels of prostaglandin E2 (PGE2) and nitric oxide (NO), due to cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) inhibition by ALA pretreatment [78]. ALA also inhibits the expression of the inflammatory cytokine IL-8 [79], inflammatory response [81].…”