Influence of genistein and diadizine on regularity of estrous cycle in cyclic female Wistar rat: interaction with estradiol receptors and vascular endothelial growth factor.

Background: Isoflavones are estrogenic compounds that exist in soy, clover, and peanuts. They are selective estrogen receptor modulators. Aim: The study was planned to explain the interactions of isoflavones with estrogen receptors alpha (ERα), beta (ERß), and vascular endothelial growth factor (VEGF) expressions in ovarian and uterine tissues during different stages of the estrous cycle of regular cyclic female Wistar rats. Methods: Thirty-two regular cyclic females were divided equally into control group: fed casein-based diet and isoflavones group: fed casein-based diet and gavaged 50 mg/kg/day soy isoflavones extract 40%. The regularity of estrus cycles was monitored. Final body weight (FBW), weight gain (BWG), and ovarian and uterine weights were estimated. Histopathology and immunohistochemistry for ERα, Erß, and VEGF in ovarian and uterine tissues were performed. Results: All females (100%, n = 16) in control group showed regularity in estrous cycle compared to 62.5% (n = 10) in isoflavones group. Estrus and diestrus phases revealed prolongation and shortening in isoflavones rats than control, respectively. Nonsignificant variation was noted in the duration of the whole cycle of both groups. FBW and BWG significantly decreased however, ovarian and uterine weights increased significantly in all estrous phases of isoflavones group than control. Histopathology demonstrated an increase in number of follicles/ovaries besides, hyperplasia and proliferation of luminal epithelium with hydropic degeneration in the isoflavones group. Also, uterine connective tissue stroma showed edema in the isoflavones group during all estrous phases. Immunostaining percentages of ERα, Erß, and VEGF protein expression were significantly elevated in the isoflavones group during all estrous phases. Conclusion: Isoflavones induced irregularity of the estrous cycle that was encountered by increased and altered ERα, Erß, and VEGF expressions in ovarian and uterine tissues.

Neuroprotective effect of duloxetine in a mouse model of diabetic neuropathy: Role of glia suppressing mechanisms.

AIMS: Painful diabetic neuropathy (PDN) is one of the most frequent complications of diabetes and the current therapies have limited efficacy. This study aimed to study the neuroprotective effect of duloxetine, a serotonin noradrenaline reuptake inhibitor (SNRI), in a mouse model of diabetic neuropathy. MAIN METHODS: Nine weeks after developing of PDN, mice were treated with either saline or duloxetine (15 or 30 mg/kg) for four weeks. The effect of duloxetine was assessed in terms of pain responses, histopathology of sciatic nerve and spinal cord, sciatic nerve growth factor (NGF) gene expression and on the spinal expression of astrocytes (glial fibrillary acidic protein, GFAP) and microglia (CD11b). KEY FINDINGS: The present results highlighted that duloxetine (30 mg/kg) increased the withdrawal threshold in von-Frey test. In addition, both doses of duloxetine prolonged the licking time and latency to jump in the hot-plate test. Moreover, duloxetine administration downregulated the spinal expression of both CD11b and GFAP associated with enhancement in sciatic mRNA expression of NGF. SIGNIFICANCE: The current results highlighted that duloxetine provided peripheral and central neuroprotective effects in neuropathic pain is, at least in part, related to its downregulation in spinal astrocytes and microglia. Further, this neuroprotective effect was accompanied by upregulation of sciatic expression of NGF.

Metformin enhancing the antitumor efficacy of carboplatin against Ehrlich solid carcinoma grown in diabetic mice: Effect on IGF-1 and tumoral expression of IGF-1 receptors.

Diabetes has been listed as a risk factor for various types of cancer. Cancer cell development can be promoted by increased levels of IGF-1 and hyperinsulinemia that are associated with diabetes type II. Metformin is an anti-diabetic agent and its potential antitumor impact has become the objective of numerous studies. In this vein, we hypothesize that using metformin in diabetes type II mice may synergistic with carboplatin for reducing the risk of cancer. Therefore, the study aimed to evaluate the in vivo antitumor activity of metformin against solid EAC tumor growth in female diabetic mice and its potential pro-apoptotic and anti-proliferative effects with clarification of its inconclusive biological mechanisms. Mice were assigned into nine groups; normal control, diabetic control, diabetic plus EAC control, EAC control, and treated groups received carboplatin and/or metformin (100, 200mg/kg). Metformin administration especially with high dose potentiated the antitumor activity of carboplatin displayed by increased pro-apoptotic activators "caspase-3 and bax" and reduced anti-apoptotic protein bcl-2. This was confirmed by the histopathological scores. Moreover, the combination therapy was effective in attenuating the expression of the pro-angiogenic mediator "VEGF" and the microvessel density as revealed by the CD34. Additionally, this combination down-regulated the high levels of the mutagenic element "IGF-1" and its receptor expression, and attenuated the intensity of inflammatory mediators. In conclusion, it was found that metformin therapy could enhance apoptotic marker, and suppress the neovascularization and proliferation process. This clarified the ability of metformin to support carboplatin activity in reducing tumor progression in type II diabetes.

Ameliorating effects of green tea extract on cadmium induced reproductive injury in male Wistar rats with respect to androgen receptors and caspase- 3.

Cadmium is one of the potent environmental endocrine disruptors that has adverse effects on male fertility. This study was conducted to investigate the protective role of green tea extract (GTE) on cadmium chloride (CdCl2) induced reproductive toxicities in male Wistar rats. Thirty-six male Wistar rats were divided to 4 groups, each one contained 9 rats. Control group, they were gavaged distilled water, meanwhile the treated groups gavaged CdCl2 (3mg/kg), GTE (70mg/kg) and CdCl2+GTE (3mg/kg and 70mg/kg) for 63days. In GTE+ CdCl2 treated rats, the final body weight, relative testicular weight, epididymal weight, seminal and prostate glands weights were significantly (P<0.05) increased compared to CdCl2 intoxicated rats. Sperm cell concentration was significantly (P<0.05) increased in CdCl2+GTE group, while sperm morphological abnormalities were significantly (P<0.05) decreased than CdCl2 group. The levels of superoxide dismutase (SOD) and reduced glutathione (GSH) were elevated significantly (P<0.05) in CdCl2+GTE group, meanwhile catalase activity was significantly (P<0.05) declined than CdCl2 group. Hypercholesterolemia was observed in CdCl2 group than control one while GTE+CdCl2 group revealed significant (P<0.05) reduction in cholesterol level than CdCl2 treated group. Testicular androgen receptors and caspase-3 protein expression showed marked reduction and increase (P<0.05) in CdCl2 group than control, respectively. Treatment with GTE with CdCl2 significantly (P<0.05) increased androgen receptors, while decreased caspase-3 protein than CdCl2 group. In conclusion, GTE exhibited protective effect on testes by inhibiting CdCl2 induced oxidative damage and cellular apoptosis.