Melatonin enhances captopril mediated cardioprotective effects and improves mitochondrial dynamics in male Wistar rats with chronic heart failure.

Mitochondrial dysfunction is a recent emerging research scope that proved to be involved in many cardiovascular diseases culminating in chronic heart failure (CHF), which remains one of the primary causes of morbidity and mortality. This study investigated the added cardio-protective effects of exogenous melatonin administration to conventional captopril therapy in isoproterenol (ISO) exposed rats with CHF. Five groups of Wistar rats were recruited; (I): Control group, (II): (ISO group), (III): (ISO + captopril group), (IV): (ISO + melatonin group) and (V): (ISO + melatonin/captopril group). Cardiac function parameters and some oxidant, inflammatory and fibrotic markers were investigated. Moreover; mRNA expression of mitochondrial mitophagy [parkin & PTEN induced kinase 1 (PINK1)], biogenesis [Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)], fusion [mitofusin 2 (Mfn2)] and fission [dynamin-related protein 1 (DRP-1)] parameters in rat's myocardium were evaluated. Rats' myocardium was histo-pathologically and immunohistochemically evaluated for Beclin1 and Sirt3 expression. The present study revealed that captopril and melatonin ameliorated cardiac injury, oxidative stress biomarkers, and pro-inflammatory cytokines in ISO-exposed rats. These protective effects could be attributed to mitochondrial dynamic proteins control (i.e. enhanced the mRNA expression of parkin, PINK1, PGC-1α and Mfn2, while reduced DRP-1 mRNA expression). Also, Beclin1 and Sirt3 cardiac immunoreactivity were improved. Combined captopril and melatonin therapy showed a better response than either agent alone. Melatonin enhanced myocardial mitochondrial dynamics and Sirt3 expression in CHF rats and may represent a promising upcoming therapy added to conventional heart failure treatment.

Vagal Stimulation Ameliorates Non-Alcoholic Fatty Liver Disease in Rats.

BACKGROUND: The harmful consequences of non-alcoholic fatty liver disease (NAFLD) are posing an increasing threat to public health as the incidence of diabetes and obesity increases globally. A non-invasive treatment with a range of autonomic and metabolic benefits is transcutaneous vagus nerve stimulation (tVNS). AIM OF THE STUDY: To investigate the possible preventive impacts of VNS against adult rats' NAFLD caused by a high-fat diet (HFD) and to clarify the underlying mechanisms. METHODS: A total of thirty-two adult male rats were split into two groups: the HFD-induced NAFLD group (n = 24) and the control normal group (n = 8). The obesogenic diet was maintained for 12 weeks to induce hepatic steatosis. The HFD-induced NAFLD group (n = 24) was separated into three groups: the group without treatment (n = 8), the group with sham stimulation (n = 8), and the group with VNS treatment (n = 8). VNS was delivered for 30 min per day for 6 weeks after the establishment of NAFLD using a digital TENS device. The subsequent assessments included hepatic triglyceride, cholesterol content, serum lipid profile, and liver function testing. In this context, inflammatory biomarkers (TNF-α, IL-6) and hepatic oxidative stress (MDA, SOD, and GPx) were also assessed. To clarify the possible mechanisms behind the protective benefits of VNS, additional histological inspection and immunohistochemistry analysis of TNF-α and Caspase-3 were performed. RESULTS: In the NAFLD-affected obese rats, VNS markedly decreased the rats' body mass index (BMI) and abdominal circumference (AC). Liver function markers (albumin, ALT, and AST) and the serum lipid profile-which included a notable decrease in the amounts of hepatic triglycerides and cholesterol-were both markedly improved. Additionally, oxidative stress and inflammatory indicators showed a considerable decline with VNS. Notably, the liver tissues examined by histopathologists revealed that there is evidence of the protective impact of VNS on the oxidative and inflammatory states linked to HFD-induced NAFLD while maintaining the architectural and functional condition of the liver. CONCLUSIONS: Our findings suggest that VNS may represent a promising therapeutic candidate for managing NAFLD induced by obesity. It can be considered to be an effective adjuvant physiological intervention for the obese population with NAFLD to spare the liver against obesity-induced deleterious injury.

Effect of Liraglutide on Osteoporosis in a Rat Model of Type 2 Diabetes Mellitus: A Histological, Immunohistochemical, and Biochemical Study.

Diabetic osteoporosis (DOP) is a diabetic complication associated with a significant disability rate. Liraglutide, a glucagon-like peptide-1 receptor agonist, is a promising and innovative drug for type 2 diabetes mellitus (T2DM), with potential therapeutic implications for bone disorders. This investigation examined the impact of liraglutide on osteoporosis in rats with T2DM and studied the influence of vitamin D receptor Bsm1 polymorphism on liraglutide-induced outcomes. Thirty rats were divided into control, T2DM induced by a combination of a high-fat diet and 25 mg/kg streptozotocin, and T2DM-liraglutide (T2DM treated with 0.4 mg/kg/day liraglutide) groups. After 8 weeks of liraglutide treatment, femurs and blood samples were obtained from all rats for subsequent investigations. Diabetes induced a remarkable rise in the serum levels of receptor activator of nuclear factor kappa B ligand (RANKL) and C-telopeptide of type I collagen (CTX-1) associated with a remarkable decline in osteocalcin and osteoprotegerin (OPG). Impaired bone architecture was also demonstrated by light and scanning electron microscopic study. The immune expression of OPG was down-regulated, while RANKL was up-regulated. Interestingly, the administration of liraglutide ameliorated the previous changes induced by diabetes mellitus. In conclusion, liraglutide can prevent DOP, mostly due to liraglutide's ability to increase bone growth, while inhibiting bone resorption.

Cognitive impairment in obese rat model: role of glial cells.

BACKGROUND: Obesity is a worldwide problem. Some studies revealed that it leads to deterioration of the cognitive function, regardless of age. AIM OF THE STUDY: explore the effect of obesity on cognitive function in a rat model of obesity highlighting the role of glial cells. MATERIALS AND METHODS: twenty adult male albino rats were assigned to two groups: group I: consumed normal diet, group II: consumed high-fat diet. Body Mass Index (BMI), serum glucose, insulin, HOMA IR and lipid profile were measured. Also, hippocampal expression of Brain derived neurotrophic factor (Bdnf), synapsin, Ionized calcium binding adaptor molecule 1 (Iba), nuclear factor erythroid -related factor 2 (Nrf2), Myelin basic protein (Mbp) were measured by real-time polymerase chain reaction. The Morris Water Maze is a test used to assess spatial learning and memory capacities of rats. RESULTS: There was a high significant increase in lipid profile, serum glucose, insulin serum levels and HOMA-IR in obese groups with impaired Morris water maze performance compared to control group. There was a significant downregulation in hippocampal Bdnf and synapsin mRNA expression. In addition to decrease in Mbp mRNA expression (P < 0.001). This could be explained by oxidative stress through significant downregulation of Nrf2 mRNA, and inflammation observed in significant upregulation Iba mRNA gene expression in the obese group. CONCLUSION: Many factors contribute to obesity associated cognitive impairment. In our study, we figured out the crucial roles of glial cells including microglial activation and oligodendrocytes affection with other underlying mechanisms including oxidative stress and hippocampal inflammation.