Abstract
There is an accumulating evidence suggesting an immunomodulatory role of 1 alpha,25(OH)(2)D3. Altered 1 alpha,25(OH)(2)D3 level may play a role in the development of T2DM and contribute to the pathogenesis of liver diseases. Our study was designed to study and compare the effect of metformin and lot,25(OH)2D3 supplementation on liver injury in type 2 diabetic rat.
Sixty male Albino rats were divided into 5 groups; group 1: control rats. the remaining rats were fed high fat diet for 2 weeks and injected with streptozotocin (35 mg/kg BW, i.p.) to induce T2DM and were divided into: group 2: untreated diabetic rats, group 3: diabetic rats treated by metformin (100 mg/kgBW/d, orally), group 4: diabetic rats supplemented by 1 alpha,25(OH)(2)D3 (0.5 mu g/kg BW, i.p.) 3 times weekly and group 5: supplemented by both 1 alpha,25(OH)(2)D3 and metformin. Eight weeks later, serum glucose and insulin levels were measured, HOMA IR was calculated, lipid profile, Ca2+, ALT and AST were estimated. Liver specimens were taken to investigate PPAR-alpha (regulator of lipid metabolism), NF-KB p65, caspase 3 and PCNA (proliferating cell nuclear antigen) and for histological examination.
The liver enzymes were elevated in the diabetic rats and the histological results revealed an injurious effect of diabetes on the liver. 1 alpha,25(OH)(2)D3, metformin and both drugs treatment significantly improved liver enzymes as compared to the untreated rats. The improvement was associated with a significant improvement in the glycemic control, lipid profile and serum Ca2+ with a significant reduction in NF-KB p65 and caspase 3 and increased PPAR-alpha, and PCNA expression as compared to the untreated group. 1 a,25(OH)2D3 induced a slightly better effect as compared to metformin. Both agents together had a synergistic action and almost completely protected the liver. Histological results confirmed the biochemical findings.
Our results showed a protective effect of 1 alpha,25(OH)(2)D3 and metformin on liver in diabetic rats as indicated by an improvement of the level of the liver enzymes, decreased apoptosis and increased proliferation and this was confirmed histologically, with modulating NFKB and PPAR-alpha. Both agents together had a synergistic effect. (C) 2016 Elsevier Ltd. All rights reserved.