ABSTRACT
Sitagliptin (SIT) is an antidiabetic used worldwide to ameliorate the hyperglycemia and insulin insensitivity induced dysmetabolism. In this study, we investigated the effect of sitagliptin and vitamin E on metabolic dysfunction in high-fat diet (HFD) fed rats. Sixty-four male rats were allocated into 8 groups (n = 8) as follow; control, control + vitamin E, control + sitagliptin, control + sitagliptin + vitamin E, HFD, HFD + vitamin E, HFD + sitagliptin and HFD + sitagliptin + vitamin E. Control groups were fed with chow diet for 15 weeks, while HFD groups were fed with HFD for the same duration. Vitamin E and sitagliptin were administered in the last 4 weeks of the study. At the end of the 15th week, body weight, liver weight/body weight ratio, weight gain, glucose, lipid profile, liver enzymes, adiponectin and pro-inflammatory cytokines as interleukin 6 (IL-6), high sensitive C reactive protein (hs-CRP) and tumour necrosis factor-α (TNF-α) were measured. Additionally, gene expressions of senescence marker protein 30 (SMP30), Bcl-2, and Bax were measured. Total antioxidant capacity (TAC) and thiobaribituric acid reactive substances (TBARS) were assayed. HFD increased TBARS, IL-6, hs-CRP and TNF-α significantly and decreased TAC and adiponectin. Sitagliptin produced a comparable result through increasing adiponectin, sitagliptin alone or in combination with vitamin E increased the TAC, and gene expression of SMP30 and Bcl-2 and decreased TBARS with downregulation of the overexpressed Bax. Vitamin E, as a natural antioxidant, ameliorates the oxidative stress with insignificant change in lipid profile and inflammatory cytokine levels. Concomitant sitagliptin and vitamin E reduced the hepatic dysfunction induced by HFD.
Subject(s)
Adiponectin/metabolism , Inflammation/drug therapy , Sitagliptin Phosphate/pharmacology , Vitamin E/pharmacology , Animals , Antioxidants/administration & dosage , Antioxidants/pharmacology , Biomarkers/metabolism , Cytokines/metabolism , Diet, High-Fat , Disease Models, Animal , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacology , Inflammation/pathology , Inflammation Mediators/metabolism , Male , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , Sitagliptin Phosphate/administration & dosage , Thiobarbituric Acid Reactive Substances/metabolism , Vitamin E/administration & dosageABSTRACT
Multifactorial factors have been involved in atherosclerosis. An association has been shown between osteoporosis and carotid atherosclerosis. This work evaluates the effect of vitamin D on regression of atherosclerosis. Forty-eight male rabbits were divided into: Group Ia: [Standard diet + saline for 4 weeks]; Group I b: [Standard diet + a high dose of vitamin D3 daily for 4 weeks]; Group IIa: [Cholesterolenriched diet for 4 weeks]; Group IIb: [Cholesterolenriched diet + a single high dose of vit D3, daily for 4 weeks. At the end of 4 weeks, the rabbits were sacrificed for assay in serum lipid profile, C reactive protein (CRP), vitamin D3 metabolite, calcium, soluble adhesion molecules (sVCAM and sICAM) and nitrite (NO) and malondialdehyde (MDA) released from isolated aortic rings. Results showed that vitamin D produced a significant reduction in the sera of lipid profile, CRP, and adhesion molecules, associated with a non-significant change in serum calcium and a significant increase in the body level of vitamin D3. Addition of vitamin D to the incubated aortic rings of the atherosclerotic rabbits resulted in a significant increase in NO and decrease in MDA release. It could be concluded that vitamin D has anti-atherosclerotic effects, and may exert these effects by inhibiting lipid peroxidation and stimulation of nitric oxide, resulting in attenuation of the inflammatory atherosclerotic process.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Aorta/drug effects , Aortic Diseases/drug therapy , Atherosclerosis/drug therapy , Cholecalciferol/pharmacology , Animals , Anti-Inflammatory Agents/blood , Aorta/metabolism , Aortic Diseases/blood , Aortic Diseases/etiology , Atherosclerosis/blood , Atherosclerosis/etiology , Biomarkers/blood , C-Reactive Protein/metabolism , Calcium/blood , Cholecalciferol/blood , Cholesterol, Dietary , Disease Models, Animal , Intercellular Adhesion Molecule-1/blood , Lipid Peroxidation/drug effects , Lipids/blood , Male , Malondialdehyde/blood , Nitric Oxide/metabolism , Nitrites/blood , Rabbits , Time Factors , Tissue Culture Techniques , Vascular Cell Adhesion Molecule-1/bloodABSTRACT
Confirmation of tuberculosis in young children is difficult as they seldom expectorate sputum. Gastric aspirates are invasive and stressful and like laryngeal swabs are seldom smear positive. Induction of sputum by nebulised hypertonic saline (3%) was attempted in 30 Malawian children aged 3-15 years and was successful in 29. Four sputa were smear positive and Mycobacterium tuberculosis was cultured from three of them. A further four sputa were culture positive though smear negative. In all, the diagnosis of tuberculosis was confirmed in eight (28%) of 29 children. The presence of polymorphonuclear cells in the specimen was indicative of sputum, in contrast to epithelial cells which originate from saliva. A predominance of polymorphonuclear cells in specimens was more common in older children and these specimens were more likely to be smear positive or culture positive. Sputum induction is a useful method for the confirmation of tuberculosis and is possible in young children.
