Hepatoprotective potential of taxifolin in type 2 diabetic rats: modulation of oxidative stress and Bcl2/Bax/Caspase-3 signaling pathway

• Published in: Molecular biology reports 2024-12, Vol.51 (1), p.897, Article 897
• Main Authors: Khadrawy, Sally M., Altoom, Naif G., Alotaibi, Abdullah G., Othman, Sarah I.
• Format: Article
• Language: English
• Subjects: Adiponectin; Animal Anatomy; Animal Biochemistry; Animals; Apoptosis; Apoptosis - drug effects; BAX protein; Bcl-2 protein; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Beta cells; Biomedical and Life Sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase-3; Cytochrome c; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Enzymatic activity; Hemoglobin; Histology; Hyperglycemia; Inflammation; Insulin; Insulin - metabolism; Interleukin 6; Life Sciences; Lipid peroxidation; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Morphology; Nicotinamide; Original Article; Oxidative stress; Oxidative Stress - drug effects; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Quercetin - analogs & derivatives; Quercetin - pharmacology; Quercetin - therapeutic use; Rats; Signal transduction; Signal Transduction - drug effects; Streptozocin; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-024-09805-x

Background Diabetes mellitus (DM) is a global metabolic problem. Several factors including hyperglycemia, oxidative stress, and inflammation play significant roles in the development of DM complications. Apoptosis is also an essential event in DM pathophysiology, -with B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) determining apoptotic susceptibility. The present study aimed to elucidate the protective effects of two doses of taxifolin (TXF) on liver damage in diabetic rats and explore the possible mechanisms of action. Methods and results DM was induced in eighteen rats through intraperitoneal injections of 50 mg/kg streptozotocin and 110 mg/kg nicotinamide. Diabetic rats received daily oral intubation of 25 and 50 mg/kg TXF for 3 months. In the untreated diabetic group, there was a significant increase in fasting and postprandial glucose levels, glycosylated hemoglobin A1C (HbA1c), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), while insulin and adiponectin levels decreased significantly. Both TXF doses mitigated hyperglycemia, regulated cytokine production, and increased insulin level. Gene expressions and protein levels of Bax, caspase 3, and cytochrome c were significantly increased, while Bcl-2 was significantly decreased in the livers of diabetic rats, effects that were significantly ameliorated after TXF treatment. The results of the TUNEL assay supported the apoptotic pathway. Additionally, TXF significantly decreased lipid peroxidation and enhanced antioxidant enzyme activity in diabetic rats. Liver enzymes and histopathological changes also showed improvement. Conclusions TXF mitigated diabetes-associated hepatic damage by reducing hyperglycemia, oxidative stress, inflammation, and modulating anti-/pro-apoptotic genes and proteins. A dose of 50 mg/kg TXF was more effective than 25 mg/kg and is recommended for consumption.