ArticleDiabetology & metabolic syndrome2022
Targeting hepatic sulfane sulfur/hydrogen sulfide signaling pathway with α-lipoic acid to prevent diabetes-induced liver injury via upregulating hepatic CSE/3-MST expression.
Article in Diabetology & metabolic syndrome, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 22 citations in OpenAlex.
- Mechanisms of probiotic action in poultry gut: Colonization resistance, bioactive metabolites, quorum sensing activity, and immunomodulation.Poultry science · 2026Review
- Toxicological profile of anti-diabetic drugs and emerging measures to reduce the toxic burden.Toxicology reports · 2026Review
- Beyond Antibiotics: Therapeutic Strategies Utilizing Probiotics and Bacteriophages Against Drug-ResistantMicroorganisms · 2026Review
- Molecular Biology: Navigating the Landscape.Current issues in molecular biology · 2026Article
- Anti-Inflammatory Effects of Alpha-Lipoic Acid Modulate Cystathionine-γ-Lyase Expression in RAW 264.7 Macrophages.International journal of molecular sciences · 2026Article
- Comprehension of the Function of Antioxidants in Targeting Different Signaling Pathways to Cure Oxidative Stress-induced Hepatotoxicity.Current topics in medicinal chemistry · 2026Review
- Therapeutic Potential of Alpha-Lipoic Acid: Unraveling Its Role in Oxidative Stress and Inflammatory Conditions.Current issues in molecular biology · 2025Review
- Review
- Type 1 diabetes mellitus and non-alcoholic fatty liver disease: a two-sample Mendelian randomization study.Frontiers in endocrinology · 2024Article
- The effect of alpha-lipoic acid supplementation on anthropometric, glycemic, lipid, oxidative stress, and hormonal parameters in individuals with polycystic ovary syndrome: a systematic review and meta-analysis of randomized clinical trials.Obstetrics & gynecology science · 2024Article
- Alpha-lipoic acid: A promising pharmacotherapy seen through the lens of kidney diseases.Current research in pharmacology and drug discovery · 2024Review
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7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDiabetes-induced liver injury is a complication of diabetes mellitus of which there are no approved drugs for effective treatment or prevention. This study investigates possible hepatoprotective effect of alpha-lipoic acid (ALA), and sulfane sulfur/hydrogen sulfide pathway as a novel protective mechanism in a rat model of type 2 diabetes-induced liver injury.
methodsThirty Sprague-Dawley rats underwent fasting for 12 h after which fasting blood glucose was measured and rats were randomly assigned to diabetic and non-diabetic groups. Type 2 diabetes mellitus (T2DM) was induced in diabetic group by administration of nicotinamide (110 mg/kg) and streptozotocin (55 mg/kg). Diabetic rats were treated daily with ALA (60 mg/kg/day p.o.) or 40 mg/kg/day DL-propargylglycine (PPG, an inhibitor of endogenous hydrogen sulfide production) for 6 weeks and then sacrificed. Liver, pancreas and blood samples were collected for analysis. Untreated T2DM rats received distilled water.
resultsHypoinsulinemia, hyperglycemia, hepatomegaly and reduced hepatic glycogen content were observed in untreated T2DM rats compared to healthy control group (p < 0.001). Also, the pancreas of untreated T2DM rats showed severely damaged pancreatic islets while liver damage was characterized by markedly increased hepatocellular vacuolation, sinusoidal enlargement, abnormal intrahepatic lipid accumulation, severe transaminitis, hyperbilirubinemia, and impaired hepatic antioxidant status and inflammation compared to healthy control rats (p < 0.01). While pharmacological inhibition of hepatic sulfane sulfur/hydrogen sulfide with PPG administration aggravated these pathological changes (p < 0.05), ALA strongly prevented these changes. ALA also significantly increased hepatic expression of hydrogen sulfide-producing enzymes (cystathionine γ-lyase and 3-mecaptopyruvate sulfurtransferase) as well as hepatic sulfane sulfur and hydrogen sulfide levels compared to all groups (p < 0.01).
conclusionsTo the best of our knowledge, this is the first experimental evidence showing that ALA prevents diabetes-induced liver injury by activating hepatic sulfane sulfur/hydrogen sulfide pathway via upregulation of hepatic cystathionine γ-lyase and 3-mecaptopyruvate sulfurtransferase expressions. Therefore, ALA could serve as a novel pharmacological agent for the treatment and prevention of diabetes-induced liver injury, with hepatic sulfane sulfur/hydrogen sulfide as a novel therapeutic target.
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