Renoprotective Effects of Alpha Lipoic Acid on Iron Overload-Induced Kidney Injury in Rats by Suppressing NADPH Oxidase 4 and p38 MAPK Signaling

Background: Myeloperoxidase (MPO) is involved in the initiation, progression, and complications of atherosclerosis in diabetic patients. Objectives: In the current study, the impact of alpha-lipoic acid (LA), a natural antioxidant and a cofactor in the enzyme complexes on MPO, catalase (CAT) and glutathione peroxidase (GPx) activity, glutathione (GSH) and malondialdehyde (MDA) level, histopathology of kidney and expression of antioxidant enzymes, superoxide dismutase (SOD), GPx and CAT which are involved in the detoxification of reactive oxygen species (ROS), was evaluated in alloxan-induced diabetic rats. Materials and Methods: In this study, 30 male Rattus norvegicus rats randomly divided into three groups; control (C), non-treated diabetic (NTD), and LA-treated diabetics (LATD) was induced by alloxan monohydrate (100mg/kg; subcutaneous [SC]). Then treatment was performed with alphaLA (100 mg/kg intraperitoneal (i.p) daily to 6 weeks). Blood sample of animals collected to measure levels of MPO, CAT and GPx activity GSH and MDA. Kidney paraffin sections were prepared to estimate histological studies and to measure quantitative gene expression SOD, GPX and CAT in kidney. Results: Induction of diabetes led to a significant increase in MPO and MDA, reduced GSH level and GPx and CAT activities (P < 0.05). However, treatment with alpha-LA led to a significant elevation in GPx, CAT and GSH levels with a reduction in MPO activities and MDA levels (P < 0.05). Furthermore, the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis results showed increased expressions of GPx, CAT and SOD enzyme in the treatment group compared with the diabetic control group. Histopathological lesions such as increased glomerular volume and lymphocyte infiltration were attenuated in the alpha-LA treated group. Conclusions: Our findings indicated that alpha-LA supplementation is effective in preventing complications induced by oxidative stress and atherosclerosis in diabetic rats.

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

10.21203/rs.3.rs-36814/v2 ◽

2020 ◽

Author(s):

Lei Chen ◽

Wensu Chen ◽

Yao Zhang ◽

Zhirong Wang

Keyword(s):

Oxidative Stress ◽

Nadph Oxidase ◽

Western Blot ◽

Lipoic Acid ◽

Right Atrial ◽

Atrial Pacing ◽

Alpha Lipoic Acid ◽

Model Group ◽

Structural Remodeling ◽

Masson Staining

Abstract Background The pathogenesis of atrial fibrillation(AF) is complex, and the treatment method is still not satisfactory. A rapid atrial pacing (RAP) model was constructed to study the effects of alpha-lipoic acid (ALA) on electrical and structural remodeling, as well as its possible mechanism in rabbits.Methods A total of 30 rabbits were randomly divided into a sham-operated group (SHAM group), a rapid atrial pacing model group (RAP group) and an alpha-lipoic acid+rapid atrial pacing model group (ALA+RAP group). Their right atriums were paced at a speed of 600 beats/min for 12 h in the RAP and ALA+RAP groups, and the atrial effective refractory period (AERP) and AERP frequency adaptability were determined during the pace. In each group, malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS) were detected to observe the effects of oxidative stress. The pathological structure of the atrial tissue was observed through HE and Masson staining. Ultrastructural changes in the atrial myocytes were observed by transmission electron microscopy (TEM), and the expression levels of Nox2 and Nox4 were detected by immunohistochemistry, western blot and ELISA.Results Through testing AERP and AERP frequency adaptability, it was found that in the early stage of rapid atrial pacing, AERP gradually shortened, while ALA injection could remarkably delay this process. Correspondingly, AERP frequency adaptability in the RAP group was reduced, and ALA could enhance it. HE staining showed that pathological changes in the ALA+RAP group were milder than those in the RAP group. And it was found that in the ALA+RAP group, the deposition of collagen in the endomysium was remarkably reduced via Masson staining. Ultrastructure injury in the ALA+RAP group showed various degrees of improvement compared with the RAP group. RAP was accompanied by an increase in oxidative stress levels, and ALA could effectively inhibit RAP-induced oxidative stress in vivo via detecting SOD, MDA and ROS. In addition, Western blot showed that the expression of NOX2 and NOX4 was upregulated in RAP group, but ALA intervention could inhibit their expression. Moreover, immunohistochemistry and ELISA also got similar results as Western blot.Conclusion ALA can inhibit atrial electrical remodeling and structural remodeling by reducing ROS production and alleviating oxidative stress injury induced by rapid right atrial pacing, and its mechanism may be related to inhibiting the activity of NADPH oxidase.

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Effect of alpha-lipoic acid on acute lung injury and acute kidney injury in major postpartum hemorrhage

Ain-Shams Journal of Anaesthesiology ◽

10.4103/1687-7934.182261 ◽

2016 ◽

Vol 9 (2) ◽

pp. 219

Author(s):

RaniaM Ali ◽

MarwaA Khairy ◽

DinaY Mansour

Keyword(s):

Acute Kidney Injury ◽

Acute Lung Injury ◽

Lung Injury ◽

Lipoic Acid ◽

Postpartum Hemorrhage ◽

Kidney Injury ◽

Alpha Lipoic Acid

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Troxerutin down-regulates KIM-1, modulates p38 MAPK signaling, and enhances renal regenerative capacity in a rat model of gentamycin-induced acute kidney injury

Food & Function ◽

10.1039/c8fo01086b ◽

2018 ◽

Vol 9 (12) ◽

pp. 6632-6642 ◽

Cited By ~ 7

Author(s):

Samir A. Salama ◽

Hany H. Arab ◽

Ibrahim A. Maghrabi

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

P38 Mapk ◽

Tissue Regeneration ◽

Rat Model ◽

Tissue Injury ◽

Kidney Injury ◽

Renal Tissue ◽

Mapk Signaling ◽

Regenerative Capacity

Troxerutin enhances renal tissue regeneration, improves renal function, and decreases renal tissue injury in gentamycin-treated rats.

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NADPH oxidase 4 mediates TGF-β1/Smad signaling pathway induced acute kidney injury in hypoxia

PLoS ONE ◽

10.1371/journal.pone.0219483 ◽

2019 ◽

Vol 14 (7) ◽

pp. e0219483 ◽

Cited By ~ 2

Author(s):

Sungkwon Cho ◽

Seong-Lan Yu ◽

Jaeku Kang ◽

Bo Young Jeong ◽

Hoi Young Lee ◽

...

Keyword(s):

Acute Kidney Injury ◽

Nadph Oxidase ◽

Signaling Pathway ◽

Kidney Injury ◽

Smad Signaling ◽

Nadph Oxidase 4 ◽

Smad Signaling Pathway ◽

Tgf Β1

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

10.21203/rs.3.rs-36814/v1 ◽

2020 ◽

Author(s):

Lei Chen ◽

Wensu Chen ◽

Yao Zhang ◽

Zhirong Wang

Keyword(s):

Oxidative Stress ◽

Nadph Oxidase ◽

Lipoic Acid ◽

Right Atrial ◽

Ultrastructural Changes ◽

Atrial Pacing ◽

Alpha Lipoic Acid ◽

Model Group ◽

Stress Injury ◽

Structural Remodeling

Abstract Background The pathogenesis of atrial fibrillation(AF) is complex, and the treatment method is still not satisfactory. A rapid atrial pacing (RAP) model was constructed to study the effects of alpha-lipoic acid (ALA) on electrical and structural remodeling, as well as its possible mechanism in rabbits.Methods A total of 30 rabbits were randomly divided into a sham-operated group (SHAM group), a rapid atrial pacing model group (RAP group) and an alpha-lipoic acid+rapid atrial pacing model group (ALA+RAP group). Their right atriums were paced at a speed of 600 beats/min for 12 h in the RAP and ALA+RAP groups, and the atrial effective refractory period (AERP) and AERP frequency adaptability were determined during the pace. In each group, malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS) were detected to observe the effects of oxidative stress. The pathological structure of the atrial tissue was observed through HE and Masson staining. Ultrastructural changes in the atrial myocytes were observed by transmission electron microscopy (TEM), and the expression levels of Nox2 and Nox4 were detected by immunohistochemistry, western blot and ELISA.Conclusion ALA can inhibit atrial electrical remodeling and structural remodeling by reducing ROS production and alleviating oxidative stress injury induced by rapid right atrial pacing, and its mechanism may be related to inhibiting the activity of NADPH oxidase.

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