Hyperthyroidism-induced cardiac disease is an evolving health, economic, and social problem affecting well-being. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2-I) have been proven to be cardio-protective when administered in cases of heart failure. This study intended to investigate the potential therapeutic effect of SGLT2-I on hyperthyroidism-related cardiopulmonary injury, targeting the possible underlying mechanisms. The impact of the SGLT2-I, dapagliflozin (DAPA), (1 mg/kg/day, p.o) on LT4 (0.3 mg/kg/day, i.p)-induced cardiopulmonary injury was investigated in rats. The body weight, ECG, and serum hormones were evaluated. Also, redox balance, DNA fragmentation, inflammatory cytokines, and PCR quantification in heart and lung tissues were employed to investigate the effect of DAPA in experimentally induced hyperthyroid rats along with histological and immunohistochemical examination. Coadministration of DAPA with LT4 effectively restored all serum biomarkers to nearly average levels, improved ECG findings, and reinstated the redox balance. Also, DAPA could improve DNA fragmentation, elevate mtTFA, and lessen TNF-α and IGF-1 gene expression in both organs of treated animals. Furthermore, DAPA markedly improved the necro-inflammatory and fibrotic cardiopulmonary histological alterations and reduced the tissue immunohistochemical expression of TNF-α and caspase-3. Although further clinical and deep molecular studies are required before transposing to humans, our study emphasized DAPA’s potential to relieve hyperthyroidism-induced cardiopulmonary injury in rats through its antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as via antagonizing the sympathetic over activity.

The current study was designed to investigate the anti-hyperglycemic and antioxidant effects of berberine (BBR) in high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic rats, focusing on the role of adipose tissue peroxisome proliferator activated receptor gamma (PPARγ), resistin and inflammatory cytokines. Type 2 diabetes was induced by feeding rats with HFD for 4 weeks followed by a single intraperitoneal injection of 35 mg/kg body weight STZ. Diabetic rats were supplemented with 50 and 100 mg/kg BBR orally for 4 weeks. HFD/STZ-induced diabetic rats showed a significant increase in serum glucose and fructoseamine, and significant decrease in body weight and serum insulin. Serum pro-inflammatory cytokines were significantly increased in serum of the diabetic rats. BBR significantly ameliorated body weight, and serum glucose, insulin and pro-inflammatory cytokines. In addition, diabetic rats exhibited a significant increase in liver lipid peroxidation and nitric oxide levels, and declined antioxidant defenses, an effect that was reversed following treatment with BBR. Adipose tissue PPARγ mRNA was significantly down-regulated while resistin mRNA was markedly up-regulated in diabetic rats. BBR treatment significantly ameliorated both PPARγ and resistin mRNA expression. In conclusion, BBR attenuates hyperglycemia and its associated oxidative stress and inflammation, possibly through potentiation of the antioxidant defenses and up-regulation of PPARγ expression.

Background: High fat-fructose diet is a proinflammatory diet that increases risk of hepatocytes and myocytes steatosis and fibrosis. Finding anti-inflammatory strategies to fight these harmful effects is paid attention to nowadays. This study compared the effects of two widely anti-inflammatory interventions—metformin and intermittent fasting on myocytes and hepatocyte injury induced by proinflammatory diet and tracking possible underlying mechanisms. In this work, rats fed high fat-fructose diet were subdivided into untreated group, treated by metformin, and/or intermittent fasting. Results: Metformin (300 mg/kg/day) and intermittent fasting (3 days/week) specially their combination for 4 weeks showed significant improvement in insulin resistance, lipid profile, antioxidants (p < 0.05), as well as enhanced hepatocytes and myocytes repair and reduced collagen deposition through upregulation of mitophagy-related genes: PINK1, PARKIN, LAMP2, and PPAR-α (p < 0.05). Conclusions: Intermittent fasting has beneficial metabolic and molecular therapeutic effects against proinflammatory diet-induced injury. Their results are like those of metformin sparing its adverse effects. Their combination showed additional effects against diet-induced myocytes and hepatocyte injury by upregulation of mitophagy-related genes without the need of increasing the dose of metformin. Graphic