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Ahmet Sahan Cem Akbal Hasan Huseyin Tavukcu Ozge Cevik Sule Cetinel Cagrı Akın Sekerci Tarik Emre Sener Goksel Sener Yiloren Tanidir 《Andrologia》2020,52(9):e13639
A review of the literature indicated that sirtuin-1 expression, a regulator of nitric oxide bioavailability in erectile dysfunction (ED) after melatonin therapy, has not yet been investigated. The objective of this study was to evaluate the protective effects of melatonin for erectile function with sirtuin-1 protein expression in type 1 diabetic rat models. Fifty male Sprague Dawley rats were placed into five groups. Except for those in the control group (C), each animal received a single dose (60 mg/kg) of streptozotocin to induce diabetes. The animals were placed into the diabetes (D) group, insulin (I) group (6 U/kg/day), melatonin (Mel) group (10 mg kg−1 day−1) and combined treatment (I + Mel) group. Ten weeks later, the serum testosterone levels, intracavernosal pressure (ICP), mean arterial pressure (MAP), malondialdehyde (MDA), cyclic guanosine monophosphate (c-GMP), 8-hydroxydeoxyguanosine (8-OHdG), nitric oxide synthase (NOS), caspase-3 activity, sirtuin-1 and endothelial nitric oxide synthase (eNOS) protein expression and histological findings were assessed. The mean ICP/MAP ratio for the D group was lower than the mean ratios for the other groups. The treatment groups, particularly the I + Mel group, exhibited lower 8-OHdG and MDA levels and caspase-3 activity than the D group. The sirtuin-1 and eNOS expression and cavernosal tissue (CT) histology seemed to have been preserved by the melatonin and/or insulin therapy. These results were indicative of a profound protective effect of melatonin by the activation of sirtuin-1 protein expression against hyperglycemia-induced oxidative CT injury. 相似文献
3.
Summary In mice, an experimental autoimmune diabetes can be induced by multiple injections with low doses of streptozotocin. Since different mouse strains show a varying susceptibility towards this treatment, we have examined whether the experimental autoimmune diabetes is under the genetic control of the major histocompatibility complex (H-2 complex). Mice of five congenic resistant strains, differing in their genome only at the H-2 region, were identically treated on five consecutive days with 40 mg streptozotocin/kg body weight. Genes at the H-2 complex were found to determine the susceptibility towards the diabetogenic effect of streptozotocin: mice of H-2 haplotype k (B10.BR) developed persistent and strong hyperglycaemia (blood glucose approximately 17 mmol/1), mice of strain B10.A (H-2a), C57BL/10 (H-2b) and B10.D2 (H-2d) reacted with moderate hyperglycaemia (between 11.5 and 15.5 mmol/1), whereas mice of strain B10.S (H-2s) were resistant to the diabetogenic effect of low-dose streptozotocin except for a small and transient rise of blood glucose levels. It is concluded that genes within the major histocompatibility complex affect the diabetogenic response to multiple low-dose streptozotocin treatment. 相似文献
4.
Cerebrolysin reverses hippocampal neural atrophy in a mice model of diabetes mellitus type 1 下载免费PDF全文
Lizzette Sanchez‐Vega Ismael Juárez Maria De Jesus Gomez‐Villalobos Gonzalo Flores 《Synapse (New York, N.Y.)》2015,69(6):326-335
The animal model of streptozotocin‐induced diabetes mellitus type 1 (DM1) is used to study neuronal and behavioral changes produced by an increase in blood‐glucose levels. Our previous report showed that chronic streptozotocin administration induced atrophy of dendritic morphology of pyramidal neurons of the CA1 dorsal hippocampus. In addition, we showed that Cerebrolysin (Cbl), a neurotrophic peptide mixture, reduces the dendritic atrophy in animal models of aging. This study aimed to determine whether Cbl was capable of reducing behavioral and neuronal alterations, after 6 weeks of hyperglycemia in mice (streptozotocin‐induced DM1). The levels of glucose in the blood were evaluated before and after streptozotocin administration and only animals with more than 240 mg/dL of blood‐levels of glucose were used. After streptozotocin treatment, the mice received 6 weeks of Cbl, locomotor activity was measured and dendritic morphological changes were evaluated using Golgi‐Cox stain procedure, and analyzed by the Sholl method. In mice treated with streptozotocin there was a clear reduction in the dendritic length of pyramidal neurons of the CA1 and granular cells of the dental gyrus of the dorsal hippocampus. Interestingly, Cbl reversed the morphological changes induced by streptozotocin. Our results extend the list of abnormal morphological changes detected in this model of DM, and support the possibility that Cbl may have beneficial effects in the management of brain alterations induced by DM. Synapse 69:326–335, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
5.
T Walter B van Brakel C Vercherat V Hervieu J Forestier J-A Chayvialle Y Molin C Lombard-Bohas M-O Joly J-Y Scoazec 《British journal of cancer》2015,112(3):523-531
Background:
O6-Methylguanine-DNA methyltransferase (MGMT) loss of expression has been suggested to be predictive of response to temozolomide in neuroendocrine tumours (NETs), but so far, only limited data are available. We evaluated the prognostic and predictive value of MGMT status, assessed by two molecular methods and immunohistochemistry, in a large series of NETs of different origins.Methods:
A total of 107 patients, including 53 treated by alkylants (temozolomide, dacarbazine or streptozotocin), were retrospectively studied. In each case, we used methyl-specific PCR (MS-PCR) and pyrosequencing for evaluation of promoter methylation and immunohistochemistry for evaluation of protein status.Results:
MGMT promoter methylation was detected in 12 out of 99 (12%) interpretable cases by MS-PCR and in 24 out of 99 (24%) by pyrosequencing. O6-Methylguanine-DNA methyltransferase loss of expression was observed in 29 out of 89 (33%) interpretable cases. Status of MGMT was not correlated with overall survival (OS) from diagnosis. Progression-free survival and OS from first alkylant use (temozolomide, dacarbazine and streptozotocin) were higher in patients with MGMT protein loss (respectively, 20.2 vs 7.6 months, P<0.001 and 105 vs 34 months, P=0.006) or MGMT promoter methylation assessed by pyrosequencing (respectively, 26.4 vs 10.8 months, P=0.002 and 77 vs 43 months, P=0.026).Conclusions:
Our results suggest that MGMT status is associated with response to alkylant-based chemotherapy in NETs. 相似文献6.
ObjectiveDiabetic kidney disease (DKD) is the leading cause of death and disability of diabetes mellitus. However, there is still a lack of specific drugs for the treatment of DKD. The chief aim of this research is to investigate the role and mechanism of 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) for DKD.MethodsWild type and TLR4 knockout mice were induced to diabetes. After 4-week treatment with DMDD, blood sugar, renal function, blood lipid and pathological changes were assessed. Real-time PCR, western blotting, and immunohistochemistry were employed to detect the expressions of TLR4, TGFβ1 and Smad2/3 in the renal tissue.ResultsDMDD improved the serum lipid and decreased fasting blood glucose levels in diabetic mice. CysC and urinary albumin levels increased markedly in the diabetic group, and they were obviously decreased after 4 weeks of DMDD treatment. Compared with the WT diabetic mice, the urinary albumin and CysC in the TLR4-/- mice were expressed at lower levels. HE and Masson’s staining revealed that DMDD clearly ameliorated pathological changes and renal fibrosis. When TLR4 gene was knock out, the pathological was improved. Mechanistically, TLR4, TGF-β1 and Smad2/3 were obvious up-regulation in the renal tissues of diabetic mice. The expressions of these proteins were significantly down-regulated after DMDD treatment (p < 0.05). In the TLR4-/- mice, mRNA and protein levels of TGF-β1 and Smad2/3 were obviously lower than those in the WT mice. In addition, IHC revealed that a strong in situ expressions of TLR4, TGF-β1 and Smad2/3 were seen in the kidney tissues of diabetic mice, which were distinctly weakened in the DMDD-treated mice. In the TLR4-/- mice, however, expressions of TGF-β1 and Smad2/3 were not remarkable increase in the diabetic mice compared with normal mice.ConclusionsThese results strongly indicate that TLR4 is essential for DMDD protection against renal dysfunction in diabetic mice. Its hypoglycemic and anti-fibrosis effects were likely mediated by the TLR4/TGFβ signaling pathway. 相似文献
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Matthew W McDonald Michael R Murray Katharine E Hall Earl G Noble CW James Melling 《Islets》2014,6(2)
Regular exercise has been shown to improve many complications of Type 1 diabetes mellitus (T1DM) including enhanced glucose tolerance and increased cardiac function. While exercise training has been shown to increase insulin content in pancreatic islets of rats with T1DM, experimental models were severely hyperglycemic and not undergoing insulin treatment. Further, research to date has yet to determine how exercise training alters glucagon content in pancreatic islets. The purpose of the present investigation was to determine the impact of a 10-week aerobic training program on pancreatic islet composition in insulin-treated rats with T1DM. Second, it was determined whether the acute, exercise-mediated reduction in blood glucose experienced in rats with T1DM would become larger in magnitude following aerobic exercise training. Diabetes was induced in male Sprague-Dawley rats by multiple low dose injections of streptozotocin (20mg/kg i.p.) and moderate intensity aerobic exercise training was performed on a motorized treadmill for one hour per day for a total of 10 weeks. Rats with T1DM demonstrated significantly less islet insulin, and significantly more islet glucagon hormone content compared with non-T1DM rats, which did not significantly change following aerobic training. The reduction in blood glucose in response to a single exercise bout was similar across 10 weeks of training. Results also support the view that different subpopulations of islets exist, as small islets (<50 μm diameter) had significantly more insulin and glucagon in rats with and without T1DM. 相似文献
9.
Yuki Kato Koichi Masuno Kae Fujisawa Noriko Tsuchiya Mikinori Torii Atsuko Hishikawa Takeshi Izawa Mitsuru Kuwamura Jyoji Yamate 《Experimental and toxicologic pathology》2017,69(7):413-423
We herein investigated the histopathological features, including proliferative activity and immunoexpression, of pancreatic islet cell tumors (ICTs) in male SD rats induced by streptozotocin (STZ) and nicotinamide (NA), and discussed their relevance to biological behaviors and prognoses. A total of 70 and 43% of rats developed ICTs 37–45 weeks after the treatment with STZ (50 or 75 mg/kg, i.v.) and NA (350 mg/kg, twice, p.o.), respectively. Among the islet tumors observed in the STZ/NA-treated groups, 75% were adenomas, while 25% were carcinomas. Most STZ/NA-induced carcinomas were characterized by well-differentiated tumor cells with/without local invasion into the surrounding tissues, and weak proliferative activity. No outcome such as distance metastasis and death was noted. All of the ICTs strongly expressed insulin, part of which had hormone productivity; however there were no hypoglycemia-related clinical signs such as convulsion in these rats 36 weeks after the treatment. These results suggested that rat ICTs induced STZ/NA have small impact on biological activity or prognosis. STZ/NA treatment significantly increased of focal proliferative lesions in the kidney, liver and adrenal glands other than pancreatic islets. Of the STZ/NA-induced kidney tumors, more than 60% were renal cell adenomas, and many of them were basophilic type. The incidence of eosinophilic or clear cell type of tumors was less than 10%, respectively. Immunohistochemical analyses revealed that many of the STZ/NA-induced basophilic type of renal tumors were derived from proximal tubules, whereas the clear cell and eosinophilic types were derived from collecting tubules. 相似文献
10.
Naohiro Iwata Mari Okazaki Meiyan Xuan Shinya Kamiuchi Hirokazu Matsuzaki Yasuhide Hibino 《Nutrients》2014,6(4):1554-1577
Diabetes mellitus is known to exacerbate cerebral ischemic injury. In the present study, we investigated antiapoptotic and anti-inflammatory effects of oral supplementation of ascorbic acid (AA) on cerebral injury caused by middle cerebral artery occlusion and reperfusion (MCAO/Re) in rats with streptozotocin-induced diabetes. We also evaluated the effects of AA on expression of sodium-dependent vitamin C transporter 2 (SVCT2) and glucose transporter 1 (GLUT1) after MCAO/Re in the brain. The diabetic state markedly aggravated MCAO/Re-induced cerebral damage, as assessed by infarct volume and edema. Pretreatment with AA (100 mg/kg, p.o.) for two weeks significantly suppressed the exacerbation of damage in the brain of diabetic rats. AA also suppressed the production of superoxide radical, activation of caspase-3, and expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) in the ischemic penumbra. Immunohistochemical staining revealed that expression of SVCT2 was upregulated primarily in neurons and capillary endothelial cells after MCAO/Re in the nondiabetic cortex, accompanied by an increase in total AA (AA + dehydroascorbic acid) in the tissue, and that these responses were suppressed in the diabetic rats. AA supplementation to the diabetic rats restored these responses to the levels of the nondiabetic rats. Furthermore, AA markedly upregulated the basal expression of GLUT1 in endothelial cells of nondiabetic and diabetic cortex, which did not affect total AA levels in the cortex. These results suggest that daily intake of AA attenuates the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to anti-apoptotic and anti-inflammatory effects via the improvement of augmented oxidative stress in the brain. AA supplementation may protect endothelial function against the exacerbated ischemic oxidative injury in the diabetic state and improve AA transport through SVCT2 in the cortex. 相似文献