الفهرس 
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Abstract
In this study, the role of vitamin D in prevention of dexamethasone undesirable adverse effects focusing on metabolic disturbance and gastric ulceration was studied. We also evaluated the mechanisms by which dexamethasone induced these side effects and how vitamin D prevented them.
Materials & Methods:
Intervention was performed twice with 2 months interval. In each one, 24 adult male wistar albino rats were included. Animals were randomly allocated into 4 groups each one contains 6 rats and they were housed six per cage.
1- group 1: (the control group) which was given distilled water for 2 weeks.
2- group 2: (1,25dihydroxycholecalciferol (Vit D) group) which was given 1,25dihydroxycholecalciferol only as 1.25 μg /kg /day intraperitoneally for 2 weeks.
3- group 3: (Dexamethasone (Dexa) group) which was given dexamethasone as 1mg/kg/day IP for 2 weeks.
4- group 4: (Dexamethasone + 1,25dihydroxycholecalciferol( Dexa+vit D) group) which was given dexamethasone as 1 mg/kg/day combined with 1,25-(OH)2D3 (1.25 μg /kg /day) i.p for 2 weeks.
Body weight and blood pressure were measured at the beginning and at the end of the study. At the end of the study, rats were fasted for 12 hours and samples were taken for biochemical and histopathological analysis.
In order to study the beneficial effects of vitamin D on prevention of dexamethasone induced side effects, we measured body weight, assessed CHO metabolism by evaluation of fasting serum glucose, insulin, HOMA-IR, HOMA-B and glucose uptake in gastrocnemius muscle. For lipid metabolism, serum triglycerides, cholesterol, LDL and HDL were measured. For protein metabolism, gastrocnemius muscle weight and protein content were measured. We also measured BP, NO, markers for oxidative stress (serum SOD and MDA), AT1gene expression in aorta and serum electrolytes (Na+, K+ and Ca++). For gastric ulceration, we evaluated ulcer index, gastric oxidative stress (SOD, GSH and MDA) and histopathological examination of stomachs was performed.
Results:
Administration of dexamethasone in the 2 stages resulted in significant decrease of body weight, metabolic disturbance represented in significant increase of fasting serum glucose, insulin, HOMA-IR and significant decrease of HOMA-B and glucose uptake in muscle as compared to control (P>0.05). It also caused dyslipidemia in the form of significant increase of serum triglycerides, cholesterol, LDL and significant decrease of HDL (P>0.05). It decreased gastrocnemius muscle weight and protein content as compared to control (P>0.05). It caused significant elevation of BP, decrease of NO, SOD and increased MDA (P>0.05) showing increased oxidative stress. There was increased AT1 gene expression reflecting activation of renin angiotensin system (P>0.05). No change of Na+ or K+ level was found but significant hypocalcemia was detected. Regarding gastric ulcer, dexamethasone caused significant elevation of ulcer index, gastric oxidative stress (decreased SOD, GSH and increased MDA) and showed gastric mucosal ulcers in histopathological examination.
Giving vitamin D with dexamethasone resulted in partial protection against dexamethasone metabolic disturbance and gastric ulcer in most of parameters. Vitamin D caused significant increase of body weight, decrease of fasting serum glucose, insulin, HOMA-IR and significant increase of HOMA-B and glucose uptake in muscle as compared to dexa group (P>0.05). It also prevented dyslipidemia in the form of significant decreasing serum triglycerides, cholesterol, LDL and significant increase of HDL as compared to dexa group (P>0.05). It also increased gastrocnemius muscle weight and protein content as compared to dexa group (P>0.05).
There was significant decrease of BP, increase of NO, SOD and decreased MDA showing decreased oxidative stress in rats given vitamin D + Dexa as compared to dexa group (P>0.05). Vitamin D also decreased AT1 gene expression as compared to dexa group (P>0.05). No change of Na+ or K+ level was found but significant increase of Ca++ level was detected and reached the control value in Vitamin D+Dexa group as compared to dexa group (P>0.05).
Regarding gastric ulcer, vitamin D caused significant decrease of ulcer index, gastric oxidative stress (increased SOD, GSH and decreased MDA) as compared to dexa group and improved the histopathological examination of stomach showing only gastric mucosal focal erosions.
Conclusion:
from the results of the present study, the following can be concluded:
Giving vitamin D with dexamethasone helped in prevention of dexamethasone induced metabolic disturbance and gastric ulceration with significant improvement of parameters measured for CHO, lipid and protein metabolism besides, BP, electrolytes, ulcer index, oxidative stress and histopathological examination of stomach in vitamin D + Dexa group when compared to the rats given dexamethasone only.
This protection against dexamethasone induced adverse effects can be explained mainly by the antioxidant properties of vitamin D and its role in inhibition of renin angiotensin system.
Recommendations:
Vitamin D is recommended to be given with larger dose or longer duration with monitoring of calcium level in trial of obtaining complete protection against dexamethasone side effects without hypercalcemia. More parameters are needed to be measured to give more explanation about the mechanisms of dexamethasone induced side effects and vitamin D protection. The trial will be needed to be performed on human being to see if vitamin d will give the same protection against dexamethasone induced adverse effects.