RESUMO
Diabetes is one of the leading causes of endometrial diseases in women. No study has addressed the influence of hydrogen sulphide (H2S) donors on endometrial injury on top of type 1 diabetes. This research was conducted to study either the effect of sodium hydrosulphide (NaHS), the H2S donor, or DL-propargylglycine (PAG), the inhibitor of endogenous H2S production, on the endometrium of diabetic rats. A total of 40 female Wistar rats were separated into control group, diabetic group, diabetic group treated with NaHS and diabetic group treated with PAG. Serum levels of insulin, glucose, total cholesterol (TC) and triglycerides (TG) were assessed. Uterine tissue markers of oxidative stress, inflammation, apoptosis and cell proliferation were analysed. Diabetes-induced endometrial overgrowth associated with oxidative stress, inflammation and inhibition of apoptosis. NaHS administration reversed the previous conditions while PAG administration got them worse. We concluded that H2S prevented endometrial overgrowth in a rat model of type 1 diabetes through modulation of PPARγ/mTOR and Nrf-2/NF-κB pathways.
RESUMO
BACKGROUND: Myocardial necrosis is one of the most common cardiac and pathological diseases. Unfortunately, using the available medical treatment is not sufficient to rescue the myocardium. So that, we aimed in our model to study the possible cardioprotective effect of roflumilast (ROF) in an experimental model of induced myocardial injury using a toxic dose of isoprenaline (ISO) and detecting the role of vascular endothelial growth factor/endothelial nitric oxide synthase (VEGF/eNOS) and cyclic guanosine monophosphate/cyclic adenosine monophosphate/ sirtuin1 (cGMP/cAMP/SIRT1) signaling cascade. MATERIALS AND METHODS: Animals were divided into five groups; control, ISO given group (150 mg/kg) i.p. on the 4th and 5th day, 3 ROF co-administered groups in different doses (0.25, 0.5, 1 mg/kg/day) for 5 days. RESULTS: Our data revealed that ISO could induce cardiac toxicity as manifested by significant increases in troponin I, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), and cleaved caspase-3 with toxic histopathological changes. Meanwhile, there were significant decreases in reduced glutathione (GSH), total antioxidant capacity (TAC), VEGF, eNOS, cGMP, cAMP and SIRT1. However, co-administration of ROF showed significant improvement and normalization of ISO induced cardiac damage. CONCLUSION: We concluded that ROF successfully reduced ISO induced myocardial injury and this could be attributed to modulation of PDE4, VEGF/eNOS and cGMP/cAMP/SIRT1 signaling pathways with antioxidant, anti-inflammatory, and anti-apoptotic properties.
