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.

Dietary high-fructose reduces barrier proteins and activates mitogenic signalling in the testis of a rat model: Regulatory effects of kefir supplementation.

There are limited data on the influence of fructose rich diet on the male reproductive system. Kefir may have health beneficial effects, but its mechanism of action remains mostly unclear. Herein, we investigated the impact of dietary high fructose on tight junction proteins and mitogenic pathways in rat testis as well as their modulation by kefir supplementation. Twenty-two male Wistar rats (4 weeks old) were divided into the following three groups: Control; Fructose; Fructose + Kefir. Fructose was added to drinking water at concentration of 20% and administered to the rats for 15 weeks and kefir was supplemented by gavage once a day during final 6 weeks. Dietary fructose-induced testicular degeneration was associated with the downregulation of the blood-testis barrier proteins, claudin-11 and N-cadherin as well as SIRT1 expression in testicular tissue of rats. However, p38MAPK, p-p38MAPK and p-ERK1/2 levels were increased in testis of fructose-fed rats. Interestingly, JNK1 and p-JNK1 protein levels were decreased following this dietary intervention. Raf1, ERK1/2, and caspase 3 and TUNEL staining of the testis reveal the activation of apoptosis due to fructose intake. Kefir supplementation markedly promoted the expression of claudin-11, SIRT1, JNK1 and p-JNK1 but suppressed testicular mitogenic and apoptotic factors in fructose-fed rats.

High-fructose in drinking water initiates activation of inflammatory cytokines and testicular degeneration in rat.

The increased consumption of high-fructose in diet may contribute to high prevalence of metabolic syndrome in the world. The influence of high-fructose diet on male reproductive system has been poorly documented. In this study, we investigated the effects of dietary high-fructose on the expression of inflammatory cytokines in association with certain testicular proteins and sex hormones in the testis of rats. Fructose was given to the rats as 20% solution (7.8 mg/kg) in drinking water for 15 weeks. Dietary high-fructose caused testicular degeneration, also decreased testicular concentration of testosterone and right testis absolute weight. This dietary intervention increased iNOS and TNF-α mRNAs as well as iNOS, NF-κB, and p-NF-κß proteins, but decreased IL-10 and IL-6 mRNAs expressions, in testicular samples of rats. Moreover, testicular TNF-α, IL-1ß, and iNOS and plasma IL-1ß levels were significantly increased in rats fed with fructose. A marked increase in the expression level of IGF-1R protein was considered in testicular tissue of fructose-treated rats. The expression intensities of c-kit, claudin-1, and pan-cadherin were comparable in seminiferous tubules of control and fructose-treated rats. In conclusion, high-fructose intake of rats leads to activation of inflammatory cytokines, which is accompanied by testicular degeneration. These changes could be responsible for hormonal dysfunction with low intra-testicular testosterone level, which could be relevant to male infertility.

Dietary Fructose-Induced Hepatic Injury in Male and Female Rats: Influence of Resveratrol.

Purpose: Relatively little is known about gender-dependent susceptibility to hepatic injury induced by nutritional factors. In the current study, we investigated dietary fructose-induced hepatic degeneration and roles of endothelial nitric oxide synthase (eNOS), insulin receptor (IRß) and substrate-1 (IRS-1) expressions in association with inflammatory markers in male and female rats. Moreover, we examined potential effect of resveratrol on fructose-induced changes. Methods: Male and female rats were divided into 4 groups as control, resveratrol, fructose and resveratrol plus fructose. All rats were fed with a standard diet with or without resveratrol (500 mg/kg). Fructose was given as 10% in drinking waterfor 24 weeks. Results: Long-term dietary fructose caused parenchymal degeneration and hyperemia in association with impaired eNOS mRNA/protein expressions in liver of male and female rats. This dietary intervention also led to increases in hepatic triglyceride content, TNFα and IL-1ß levels in both genders. Gender-related differences to consequence of fructose consumption were not obvious. Resveratrol supplementation markedly attenuated hepatic degeneration, hyperemia and triglyceride content in association with reduced TNFα and IL-1ß levels, but enhanced IRß mRNA and IRS-1 protein, in male and female rats upon fructose feeding. Conclusion: Long-term dietary fructose causes hepatic degeneration possibly via a decrease in eNOS, but increase in TNFα and IL-1ß, in both genders. Resveratrol supplementation improved fructose-induced hepatic injury.