TY - JOUR
T1 - The protective effect of 1alpha, 25-dihydroxyvitamin d3 and metformin on liver in type 2 diabetic rats
AU - Elattar, Samah
AU - Estaphan, Suzanne
AU - Mohamed, Enas A.
AU - Elzainy, Ahmed
AU - Naguib, Mary
N1 - Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2017/10
Y1 - 2017/10
N2 - There is an accumulating evidence suggesting an immunomodulatory role of 1α,25(OH)2D3. Altered 1α,25(OH)2D3 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 1α,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 1α,25(OH)2D3 (0.5 μg/kg BW, i.p.) 3 times weekly and group 5: supplemented by both 1α,25(OH)2D3 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-α (regulator of lipid metabolism), NF-κB 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. 1α,25(OH)2D3, 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-κB p65 and caspase 3 and increased PPAR-α, and PCNA expression as compared to the untreated group. 1α,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 1α,25(OH)2D3 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-α. Both agents together had a synergistic effect.
AB - There is an accumulating evidence suggesting an immunomodulatory role of 1α,25(OH)2D3. Altered 1α,25(OH)2D3 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 1α,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 1α,25(OH)2D3 (0.5 μg/kg BW, i.p.) 3 times weekly and group 5: supplemented by both 1α,25(OH)2D3 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-α (regulator of lipid metabolism), NF-κB 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. 1α,25(OH)2D3, 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-κB p65 and caspase 3 and increased PPAR-α, and PCNA expression as compared to the untreated group. 1α,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 1α,25(OH)2D3 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-α. Both agents together had a synergistic effect.
KW - 1α,25(OH)D3
KW - Caspase-3
KW - Diabetic liver
KW - Metformin
KW - NFkB
KW - PCNA
KW - PPAR-α
UR - http://www.scopus.com/inward/record.url?scp=85007463466&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2016.11.012
DO - 10.1016/j.jsbmb.2016.11.012
M3 - Article
SN - 0960-0760
VL - 173
SP - 235
EP - 244
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
ER -