Myricetin May Improve Cardiac Dysfunction Possibly Through Regulating Blood Pressure and Cellular Stress Molecules in High-Fructose-Fed Rats.

BACKGROUND: The aim of this study was to examine the effect of myricetin on cardiac dysfunction caused by high fructose intake. METHODS: Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Myricetin was administered by oral gavage for the last 6 weeks. Systolic blood pressure was measured by tail-cuff method. The effects of isoprenaline, phenylephrine, and acetylcholine on cardiac contractility and rhythmicity were recorded in the isolated right atrium and left ventricular papillary muscles. In addition to biochemical measurements, the cardiac expressions of cellular stress-related proteins were determined by western blotting. RESULTS: Myricetin improved systolic blood pressure but did not affect body weight, plasma glucose, and triglyceride levels in fructose-fed rats. The impairment of isoprenaline- and phenylephrine-mediated increases in atrial contraction and sinus rate in fructose-fed rats was restored by myricetin treatment. Isoprenaline, phenylephrine, and acetylcholine-mediated papillary muscle contractions were not changed by fructose or myricetin administration. The expression of the mitochondrial fission marker dynamin-related protein 1 and the mitophagic marker PTEN-induced kinase 1 (PINK1) was enhanced in the fructose-fed rat, and myricetin treatment markedly attenuated PINK1 expression. High-fructose intake augmented phosphorylation of the proinflammatory molecule Nuclear factor kappa B (NF-κB) and the stress-regulated kinase JNK1, but myricetin only reduced NF-κB expression. Moreover, myricetin diminished the elevation in the expression of the pro-apoptotic Bax. CONCLUSION: Our results imply that myricetin has a protective role in cardiac irregularities induced by a high-fructose diet through reducing systolic blood pressure, improving cardiac adrenergic responses, suppressing PINK1, NF-κB, and Bax expression, and thus reflecting a potential therapeutic value.

High-fructose consumption suppresses insulin signaling pathway accompanied by activation of macrophage and apoptotic markers in rat testis.

Dietary high-fructose may cause metabolic disturbances; however, its effect on the reproductive system is little understood. The insulin signaling pathway is critical in testicular development, maintenance of microcirculation and spermatogenesis. Therefore, in this study, we aimed to investigate the impact of dietary high-fructose on insulin signaling pathway as well as macrophage and apoptotic markers in testicular tissue of rats. Fructose was administered to male Wistar rats as a 20% solution in drinking water for fifteen-week. Gene expression of ir-ß, irs-1, irs-2, pi3k, akt, mtor, and enos in the testicular samples was determined by real-time PCR. Protein expression of IR, IRS-1, IRS-2, PI3K, Akt, phospho-Akt (p-Akt), mTOR, eNOS, phospho-eNOS (p-eNOS), and GLUT5 was established by analysis of Western Blot. Testicular expression of occludin, CD163, CD68, caspase-8, and caspase-3 was analyzed by using immunohistochemical assay. Testicular level of fructose was measured by colorimetric method. Dietary high-fructose decreased mRNA expressions of irs-1, irs-2, pi3k, and mtor in the testicular tissue of rats. Also, this dietary intervention impaired protein expressions of IR, IRS-1, IRS-2, PI3K, p-Akt, mTOR, eNOS, and p-eNOS as well as p-Akt/Akt and p-eNOS/eNOS ratios in the testis of rats. However, a high-fructose diet increased the expression of CD163, CD68, caspase-8 and caspase-3, but decreased that of occludin, in the testicular tissue of rats. The high-fructose consumption in rats suppresses testicular insulin signaling but activates macrophages-related factors and apoptotic markers. These changes induced by dietary fructose could be related to male reproductive dysfunction.

The impact of dietary fructose on gut permeability, microbiota, abdominal adiposity, insulin signaling and reproductive function.

The excessive intake of fructose in the regular human diet could be related to global increases in metabolic disorders. Sugar-sweetened soft drinks, mostly consumed by children, adolescents, and young adults, are the main source of added fructose. Dietary high-fructose can increase intestinal permeability and circulatory endotoxin by changing the gut barrier function and microbial composition. Excess fructose transports to the liver and then triggers inflammation as well as de novo lipogenesis leading to hepatic steatosis. Fructose also induces fat deposition in adipose tissue by stimulating the expression of lipogenic genes, thus causing abdominal adiposity. Activation of the inflammatory pathway by fructose in target tissues is thought to contribute to the suppression of the insulin signaling pathway producing systemic insulin resistance. Moreover, there is some evidence that high intake of fructose negatively affects both male and female reproductive systems and may lead to infertility. This review addresses dietary high-fructose-induced deteriorations that are obvious, especially in gut permeability, microbiota, abdominal fat accumulation, insulin signaling, and reproductive function. The recognition of the detrimental effects of fructose and the development of relevant new public health policies are necessary in order to prevent diet-related metabolic disorders.

Epithelial and Endothelial Expressions of ACE2: SARS-CoV-2 Entry Routes.

Angiotensin converting enzyme 2 (ACE2) is a main receptor for SARS-CoV-2 entry to the host cell. ACE2 is one of the key enzymes in renin-angiotensin system and plays a vital role in the maintenance of cardiovascular function. ACE/ACE2 balance is critical in the regulation of blood pressure, electrolyte homeostasis, vascular and cardiac remodeling and inflammation. ACE2 was shown to be abundantly present in human epithelial cells of the lung and enterocytes of the small intestine as well as in endothelial cells of the arterial and venous vessels. ACE2 and TMPRSS2 are colocalized on the cell surface and produced a critical step host cell entry of SARS-CoV-2. TMPRSS2-cleaved ACE2 permits SARS-CoV-2 host cell entry however, ADAM17-cleaved ACE2 produces protective effects in several organs. Differently, basigin (CD147) was suggested as a putative alternate receptor for SARS-CoV-2 entry into endothelial cells. The intestinal ACE2 receptor is associated with the neutral amino acid transporter B0AT1 and ACE2 is necessary for the expression of this transporter on the luminal surface of intestinal epithelial cells. There is a good association between the localization of SARS-CoV-2 binding receptor ACE2 and the disease target organs in respiratory, cardiovascular and gastrointestinal systems. Decreased expression of ACE2, being a receptor for coronavirus, would prevent cellular entry of the virus thereby reducing progression of the infection. However, increased ACE2 expression produces beneficial health effects. Further studies are needed to clarify this conflicting situation. Currently, it is recommended to continue the therapy with ACE2-increasing drugs in patients with COVID-19.