Cellular Senescence and Vitamin D Deficiency Play a Role in the Pathogenesis of Obesity-Associated Subclinical Atherosclerosis: Study of the Potential Protective Role of Vitamin D Supplementation.

The exact link between obesity, vitamin D deficiency, and their relation to cellular senescence in the pathogenesis of subclinical atherosclerosis is still under debate. Therefore, the current study aims to verify the possible role of vitamin D deficiency and cellular senescence in the pathogenesis of obesity-related subclinical atherosclerosis. Moreover, it aims to investigate the possible protective role of vitamin D supplementation. Fifty-seven male albino rats were enrolled in the study and classified into four groups: negative (10) and positive control groups (10), an obese model group (24), and a vitamin-D-supplemented obese group (13). Aortic tissue samples and fasting blood samples were collected. The following biochemical investigations were performed: serum cholesterol, triglycerides, HDL-C, LDL-C, ALT, AST, CPK, CK-MB, and hs-cTnt. HOMA-IR was calculated. Moreover, serum SMP-30, 25 (OH)Vitamin D3, and eNOS were determined by the ELISA technique. Aortic gene expression of eNOS, SMP-30, and P53 was estimated by real-time qRT-PCR. Serum 25(OH) D3 and SMP-30 were lower in the obese group. In addition, the obese group showed higher serum lipid profile, HOMA-IR, eNOS, ALT, AST, CPK, CK-MB, and hs-cTnt than the control groups, while decreased levels were found in the vitamin-D-treated obese group. Gene expression of eNOS and SMP-30 were in accordance with their serum levels. A positive correlation was found between vitamin D level and SMP-30. In conclusion, obesity is associated with vitamin D deficiency and enhanced cellular senescence. They could play a role in the pathogenesis of obesity-associated subclinical atherosclerosis and endothelial dysfunction. Vitamin D supplements could play a protective role against such obesity-related comorbidity.

Study of Cellular Senescence and Vitamin D Deficiency in Nonalcoholic Fatty Liver Disease and The Potential Protective Effect of Vitamin D Supplementation.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a pathological process characterized by excessive hepatic fatty deposition with possible involvement of vitamin D deficiency and cellular senescence. The aim of this study is to investigate the pathophysiologic role of vitamin D deficiency and cellular senescence in NAFLD development. Moreover, it aims to investigate the potential protective role of vitamin D supplementation. METHODS: This is an experimental Case/Control study. Forty-five male albino rats were enrolled in this study. Animals were divided into four groups: negative and positive control groups (10 for each group), a model of NAFLD (11) and vitamin D-treated NAFLD groups (14). At the end of the experiment, all rats were subjected to the following investigation; biochemical estimation of serum 25 hydroxycholecalciferol, senescence marker protein-30 (SMP-30), lipid profile and calculation of homeostatic model of insulin resistance (HOMA-IR). RESULTS: NAFLD group shows a significant increase in glucose, insulin levels, and HOMA- IR compared with both normal controls. This finding indicates the intimate association between insulin resistance and NAFLD pathogenesis. Moreover, it was found that NAFLD group shows a significant decrease in SMP-30 level compared with normal controls. While vitamin D-treated NAFLD group shows significant increased SMP-30 and decrease in HOMA-IR in comparison with nontreated NAFLD group. CONCLUSION: Vitamin D deficiency and increased cellular senescence are key features of NAFLD. Vitamin D supplementation could play a protective role, which needs further investigation including clinical human study.

The Protective Role of Prenatal Alpha Lipoic Acid Supplementation against Pancreatic Oxidative Damage in Offspring of Valproic Acid-Treated Rats: Histological and Molecular Study.

BACKGROUND: Sodium valproate (VPA) is an antiepileptic drug (AED) licensed for epilepsy and used during pregnancy in various indications. Alpha-lipoic acid (ALA) is a natural compound inducing endogenous antioxidant production. Our study aimed to investigate the effect of prenatal administration of VPA on the pancreas of rat offspring and assess the potential protective role of ALA co-administration during pregnancy. METHODS: Twenty-eight pregnant female albino rats were divided into four groups: group I (negative control), group II (positive control, ALA treated), group III (VPA-treated), and group IV (VPA-ALA-treated). The pancreases of the rat offspring were removed at the fourth week postpartum and prepared for histological, immune-histochemical, morphometric, molecular, and oxidative stress marker studies. RESULTS: In group III, there were pyknotic nuclei, vacuolated cytoplasm with ballooning of acinar, α, and ß cells of the pancreas. Ultrastructural degeneration of cytoplasmic organelles was detected. Additionally, there was a significant increase in oxidative stress, a decrease in insulin-positive cell percentage, and an increase in glucagon positive cells in comparison to control groups. Moreover, VPA increased the gene expression of an apoptotic marker, caspase-3, with a decrease in anti-apoptotic Bcl2 and nuclear factor erythroid 2-related factor 2 (Nrf2) transcriptional factor. Conversely, ALA improved oxidative stress and apoptosis in group VI, and a consequent improvement of the histological and ultrastructure picture was detected. CONCLUSION: ALA co-administration with VPA significantly improved the oxidative stress condition, histological and morphometric picture of the pancreas, and restored normal expression of related genes, including Nrf2, caspase-3, and Bcl-2. Administration of α-lipoic acid has a protective effect against VPA-induced pancreatic oxidative damage via its cytoprotective antioxidant effect.

Effects of 17ß-estradiol and antioxidant administration on oxidative stress and insulin resistance in ovariectomized rats.

The prevalence of insulin resistance syndrome increases during menopause with the overproduction of reactive oxygen species and impairment of the free radical scavenger function. Therefore, we investigated the effects of 17ß-estradiol (E(2)) and vitamin E, as an antioxidant, on lipid peroxidation and antioxidant levels in the brain cortex and liver of ovariectomized rats as well as on insulin resistance in those rats. Forty female Sprague-Dawley rats, 3 months of age and weighing 231.5 ± 9.4 g, were divided into 4 groups: sham, ovariectomized (OVX), OVX treated with E(2) (40 µg/kg subcutaneously), and OVX treated with E(2) and vitamin E (100 mg/kg intraperitoneally). The 4 groups received the appropriate treatment every day for 8 weeks. Levels of glutathione, glutathione peroxidase, superoxide dismutase , catalase, and malondialdehyde in the brain cortex and liver of ovariectomized rats were measured. Also, fasting plasma insulin, glucose, and homeostatis model assessment of insulin resistance (HOMA-IR) were determined. Malondialdehyde increased and antioxidants (glutathione, glutathione peroxidase, catalase, superoxide dismutase) decreased in the brain cortex and liver of OVX rats. Also, fasting glucose, insulin, and HOMA-IR increased in OVX rats. E(2) and E(2) plus vitamin E decreased malondialdehyde and increased antioxidants in the brain cortex and liver of OVX rats. Moreover, they decreased fasting glucose, insulin, and HOMA-IR in ovariectomized rats. This study demonstrates that E(2) and E(2) plus vitamin E supplementation to OVX rats may improve insulin resistance, strengthen the antioxidant system, and reduce lipid peroxidation.