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Öğe Dietary high-fructose reduces barrier proteins and activates mitogenic signalling in the testis of a rat model: Regulatory effects of kefir supplementation(John Wiley and Sons Inc, 2021) Akar, Fatma; Yıldırım, Onur Gökhan; Yücel Tenekeci, Gözde; Tunç, Arda Selin; Demirel, Murşide Ayşe; Sadi, Gökhanhere 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.Öğe High-fructose consumption suppresses insulin signaling pathway accompanied by activation of macrophage and apoptotic markers in rat testis(Elsevier B.V., 2023) Yıldırım, Onur Gökhan; Güney, Ceren; Alcigir, Mehmet Eray; Akar, FatmaDietary 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-β, 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.Öğe High-fructose in drinking water initiates activation of inflammatory cytokines and testicular degeneration in rat(Taylor & Francis Inc, 2019) Yıldırım, Onur Gökhan; Sumlu, Esra; Aslan, Esra; Koca, Halit Buğra; Pektaş, Mehmet Bilgehan; Sadi, Gökhan; Akar, FatmaThe increased consumption of high-fructose in diet may contribute to high prevalence of metabolicsyndrome in the world. The influence of high-fructose diet on male reproductive system has beenpoorly documented. In this study, we investigated the effects of dietary high-fructose on the expres-sion of inflammatory cytokines in association with certain testicular proteins and sex hormones in thetestis of rats. Fructose was given to the rats as 20% solution (7.8 mg/kg) in drinking water for15 weeks. Dietary high-fructose caused testicular degeneration, also decreased testicular concentrationof testosterone and right testis absolute weight. This dietary intervention increasediNOSandTNF-amRNAs as well as iNOS, NF-jB, and p-NF-jbproteins, but decreasedIL-10andIL-6mRNAs expressions,in testicular samples of rats. Moreover, testicular TNF-a, IL-1b, and iNOS and plasma IL-1blevels weresignificantly increased in rats fed with fructose. A marked increase in the expression level of IGF-1Rprotein 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-treatedrats. In conclusion, high-fructose intake of rats leads to activation of inflammatory cytokines, which isaccompanied by testicular degeneration. These changes could be responsible for hormonal dysfunc-tion with low intra-testicular testosterone level, which could be relevant to male infertility.Öğe Lactobacillus helveticus and Lactobacillus plantarum modulate renal antioxidant status in a rat model of fructose-induced metabolic syndrome(Inst Bioloska Istrazivanja Sinisa Stankovic, 2019) Korkmaz, Ömer Adil; Sadi, Gökhan; Kocabaş, Aytaç; Yıldırım, Onur Gökhan; Sumlu, Esra; Koca, Halit Buğra; Nalbantoğlu, Barbaros; Pektaş, Mehmet Bilgehan; Akar, FatmaHigh dietary fructose intake causes a metabolic disorder and augments the risk of chronic kidney disease most likely due to oxidative stress. Probiotics could have antioxidant, antiinflammatory and immunoregulatory properties. The present study examined the influence of Lactobacillus helveticus and Lactobacillus plantarum supplementation on dietary fructose-induced metabolic changes and renal antioxidant/oxidant status of rats. Male Wistar rats were divided into four groups as follows: control; fructose; fructose plus L. helveticus; fructose plus L. plantarum. Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. The probiotic supplementation was applied by gastric gavage once a day for six weeks. Several metabolic parameters in the plasma, gene and protein expressions of the main antioxidant enzymes in renal tissues of rats were measured. Dietary fructose-induced elevations in plasma insulin, triglyceride, VLDL, creatinine as well as renal urea levels were alleviated after treatment with L. helveticus and L. plantarum. Moreover, L. helveticus and L. plantarum supplementation recovered the changes in renal protein expression level of SOD1, SOD2 and CAT. In conclusion, supplementation with L. helveticus and L. plantarum has an improving effect on specific metabolic parameters and renal antioxidative enzymes in a fructose-induced metabolic disorder.Öğe Lactobacillus plantarum and Lactobacillus helveticus modulate SIRT1, Caspase3 and Bcl-2 in the testes of high-fructose-fed rats(Istanbul Univ, 2020) Yıldırım, Onur Gökhan; Sadi, Gökhan; Akar, FatmaBackground and Aims: The influence of a high-fructose diet and probiotics on the male reproductive system and the testicular apoptotic pathway has been poorly documented. In this study, we aimed to investigate the influence of Lactobacillus plantarum and Lactobacillus helveticus supplementation on apoptotic factors such as sirtuin1, caspase3 and bcl-2 on the testicular tissue of high-fructose-fed rats. Methods: Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Gene expressions were established by real-time PCR. Protein levels were determined by Western blot analysis. Results: Fructose consumption did not change mRNA expression of SIRT1, but did resulted in a decreased protein level. Dietary fructose reduced bcl-2 mRNA and protein expressions, whereas no changes were observed in the gene and protein expression levels of factor caspase-3. Both Lactobacillus supplementations increased SIRT1 protein expression without changing the mRNA levels in fructose-fed rats. The supplementations with both probiotics produced a significant downregulation on caspase3 mRNA and protein levels. Bcl-2 proetin level increases with both probiotics supplementation while, mRNA level did not show difference in L.plantarum, but increased in L. helveticus supplementation. Conclusion: Treatments with L.plantarum and L.helveticus can reduce testicular apoptosis induced by dietary high-fructose in rats via suppressing caspase3 and promoting sirt1 and bcl-2 protein expressions.Öğe Myricetin may improve cardiac dysfunction possibly through regulating blood pressure and cellular stress molecules in high-fructose-fed rats(Turkish Society of Cardiology, 2024) Bal, Nur Banu; Güney, Ceren; Yıldırım, Onur Gökhan; Akar, Fatma; Demirel Yılmaz, EmineBackground: The aim of this study was to examine the effect of myricetin on cardiac dys- function 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 ace- tylcholine 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 acetylcho- line-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-?B) and the stress-regulated kinase JNK1, but myricetin only reduced NF-?B 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 irregulari- ties induced by a high-fructose diet through reducing systolic blood pressure, improving cardiac adrenergic responses, suppressing PINK1, NF-?B, and Bax expression, and thus reflecting a potential therapeutic value.
