Vitamin D Ameliorates the Hepatic Oxidative Damage and Fibrotic Effect Caused by Thioacetamide in Rats

Abstract

Vitamin D3 (VD3) is a sunshine hormone that regulates cellular proliferation, differentiation, apoptosis, and angiogenesis related to liver parenchyma. We used a thioacetamide (TAA)-induced hepatic fibrosis rat model in our study to investigate the beneficial roles of VD3 to overcome extensive liver fibrosis. Randomly, four equal groups (eight rats per group) underwent therapy for eight successive weeks: a control group, a group treated with TAA 100 mg/kg BW IP every other day, a group treated with VD3 1000 IU/kg BW IM every day, and a TAA+VD group treated with both therapies. Treatment with VD3 after TAA-induced hepatic fibrosis was found to alleviate elevated liver function measures by decreasing ALT, AST, and ALP activity; decreasing total bilirubin, direct bilirubin, cholesterol, and triglyceride levels; and increasing glucose and 25[OH]D3. Rats treated with VD3 showed marked decreases in MDA and increased SOD, CAT, and GSH levels. In addition, CD34 and FGF23 gene expressions were reduced after dual therapy. Liver sections from the TAA+VD group showed markedly decreased hepatic lesions, and Masson’s trichrome stain showed a marked decrease in dense bluish-stained fibrous tissue. The immunohistochemical expression of TGF-β and α-SMA showed markedly decreased positive brown cytoplasmic expression in a few hepatocytes, clarifying the antifibrotic effect of VD3 in hepatic fibrosis. In conclusion, VD3 alleviates hepatotoxicity and fibrosis caused by TAA.

Effects of Vitamin D on Asprosin Immunoreactivity Against Cyclophosphamide-Induced Liver Injury in Rats

“…Notably, TAS levels exhibited a significant increase. Similar findings to our results were reported in the previous studies regarding the impact of Vit D exposure on MDA and TOS levels [ 30 ]. As observed in this study, Vit D supplementation results in a reduction of ROS formation, an increase in the activity of antioxidant enzymes, and inhibition of lipid peroxidation [ 30 ].…”

The Combined Antioxidant Effects of N-Acetylcysteine, Vitamin D3, and Glutathione from the Intestinal–Neuronal In Vitro Model

“…Indeed, antioxidants are necessary to inhibit the generation of new free radicals to stop oxidative stress, and the administration of exogenous antioxidant chemicals can prevent ROSs from exerting their harmful effects [ 55 ]. For instance, several studies have reported the antioxidant effects of NAC [ 13 , 56 ], VitD3 [ 57 , 58 ], and Glut [ 59 , 60 ], highlighting their significant contributions to enhancing the mechanisms responsible for maintaining body homeostasis and safeguarding the health of body tissues. The data collected in this study demonstrate that the combination of NAC, VitD3, and Glut exerts a cooperative effect in all body districts analysed, indicating a possible new strategy to restore oxidative homeostasis of the body.…”

An update on animal models of liver fibrosis

“…TAA is a classic liver toxin and also a potent carcinogen and mutagen, which can induce oxidative stress and sterile inflammation, leading to acute and chronic liver injury ( 28 , 29 ). TAA induces hepatotoxicity in mice and rats at doses ≥100 mg/kg.…”

“…It is converted to metabolites TAA S-oxide and S, S-dioxide by cytochrome P450 enzymes and S, S-dioxide initiates toxicity by binding to lipids and proteins ( 24 ). TAA-induced liver injury is mainly caused by reaction metabolites secreted by TAA, which not only activate HSC, but also produce fibrinogen and growth factors, aiming to promote acute liver injury and chronic liver fibrosis ( 29 ).…”