Mohamed Refaat Mahdi

Introduction: Hyperglycemia is a major complication of diabetes mellitus (DM), a disease of glucose metabolism that associated with major organ damage. Aim of the work: The goal was to compare the preventative effects of curcumin versus combination of losartan and captopril medication on rats’ liver damage from type I diabetic. Material and methods: Fresh streptozotocin (STZ) solution, dissolved in sodium citrate buffer, was utilized by a single intraperitoneal injection (50 mg/kg body weight) to induce diabetes mellitus in rats within 15 minutes of formulation. Study groups were control group, diabetic group, diabetic group treated with captopril/losartan (C/L+D), diabetic group treated with curcumin (Cur+D), each group contains 6 randomly distributed rats. Blood samples were used to detect liver enzymes and assess markers of oxidative stress, also, paraffin liver sections were taken. Results: STZ-induced diabetic inflammation and apoptotic effects were better ameliorated by curcumin, while the combination of captopril and losartan was better in healing STZ-induced diabetic fibrosis. Recommendation: To improve biochemical and histopathological results, three drug combinations (captopril, losartan and curcumin) should be tested.

Cisplatin (CP) is a conventional chemotherapeutic agent with serious adverse effects. Its toxicity was linked to the stimulation of oxidative stress and inflammation. As a result, this study explored the protective effect of baicalein and alpha-tocopherol in nephrotoxicity induced by cisplatin. Until receiving an intraperitoneal injection of CP (3 mg/kg BW), rats were given baicalein orally 100 mg/kg for seven days or/and a single intraperitoneal injection of α-tocopherol 250 mg/kg. Renal function was tested to explore whether baicalein and α-tocopherol have any beneficial effects; blood urea nitrogen (BUN), serum creatinine, malondialdehyde (MDA) content, antioxidant activity biomarkers and histopathology of renal tissue, oxidative stress biomarkers, inflammatory response markers, and histopathological features of kidney architecture were measured. Cisplatin treatment resulted in extreme renal failure, as measured by high serum creatinine and BUN levels and severe renal changes. Cisplatin therapy resulted in increased lipid peroxidation and decreased glutathione and superoxide dismutase levels, reflecting oxidative stress. Upon treatment with α-tocopherol, baicalein, and combined therapy, there was augmentation in the antioxidant status as well as a reduction in IL-6, NF-κB, TNF, TLR2, and TLR4 and a significant increase in Keap-1 and NRF-2. The combined treatment was the most effective and the nearest to the normal status. These findings suggest that baicalein and α-tocopherol may be useful in preventing cisplatin-induced nephrotoxicity.

Pumpkin has received significant attention due to its nutritional compounds that have antioxidant, antifatigue, and anti‐inflammatory effects. This study is aimed at assessing the antidepressant‐like effect of L. Cucurbita pepo, sweet pumpkin, in an animal model of chronic unpredictable mild stress (CUMS) and investigating its effect on the histological structure of hippocampus compared to fluoxetine. Forty male albino rats assigned into the negative control, positive control (CUMS), and Flu‐treated and pumpkin‐treated groups (n = 10) were utilized in this study. Exposing rats to CUMS continued for 28 days, and treatments used were applied during the last 14 days of exposure. Behavioral, biochemical, and histopathological changes were assessed after 28 days. In this study, pumpkin significantly reduced the immobility time (p = 0.02), corticosterone (p < 0.001), TNF‐α, IL‐6 (p < 0.001), and malondialdehyde (p = 0.003), whereas it significantly increased the level of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) in the serum of rats exposed to CUMS. Pumpkin markedly relieved the degenerative and atrophic changes observed in the CA3 region and the dentate gyrus of the hippocampus. It significantly reduced caspase‐3 and increased glial fibrillary acidic protein (GFAP) immunoexpression in the CA3 and DG. In conclusion, administration of pumpkin extract improved the behavioral, biochemical, and hippocampal pathological alternations induced in rats after exposure to CUMS in a comparable pattern to fluoxetine. This study highlighted the potential efficacy of pumpkin in alleviating depression disorder either alone or in conjugation with conventional antidepressant therapy.

The present study aims to find out the possible protective effect of abscisic acid (ABA) on the development of diabetic cardiomyopathy (DCM) in type 2 diabetic rats. Materials and methods: Fifty male rats divided into: normal control group, diabetic group and three diabetic treated groups with either pioglitazone, or ABA, or both pioglitazone and ABA for 16 weeks. At the end of experiment, ECG was recorded, biochemical measurement of serum glucose, insulin, lipid profile, troponin I, creatine kinase MB (CK-MB), Lactate dehydrogenase (LDH), interleukin-1 beta (IL-1β) and tumor necrosis factor- alpha (TNF-α) was done, caspase 3 and 9 activity in heart, RT- PCR for connexin-43(Cx43) and histopathological examination of cardiac tissue. Results: Treatment with ABA exerted positive effects on blood glucose and insulin levels that found to be reflected on heart weight/body weight ratio in diabetic rats. Also, it exerted significant improvement in cardiac markers and pro-inflammatory cytokines. DCM is associated with increased myocyte cell death that indicated by increasing caspase 3 and 9 that improved significantly by ABA. Also, results indicated that myocardial Cx43 mRNA levels were lesser in diabetic versus non-diabetic rats. Cx43 deterioration in diabetics may be behind the prolongation of the QRS and QTc, that improved by ABA. The histopathological findings showed that ABA improved diabetic cardiomyocyte necrosis and fibrosis. Conclusion: The diabetic rats benefit from ABA intake due to its hypoglycemic, anti-inflammatory and anti-apoptotic effects. So, intake of ABA in combination with anti-diabetic drugs may be beneficial for the management of type 2 diabetes mellitus.

Endothelin system members including endothelin-1, endothelin-2, endothelin-3, endothelin receptors, and endothelin converting enzyme are considered major regulating factors in cancer cell biology and cancer microenvironment. Endothelins are members of the matrix metalloproteinase superfamily of proteases, which are released from pre-proteins, bind to their receptors with differential affinity, and are degraded following cellular uptake. For their structural similarity, endothelin-2 and endothelin-3 can be regarded as natural competitors for the endothelin-1 receptors and as natural antagonists of endothelin-1. Endothelin-1 is regulated at several levels, primarily at the level of transcription. Remarkably, endothelin-1 is overexpressed in colorectal cancer, and elevated plasma levels were found in colorectal cancer patients. Endothelin receptor type A has an unequal distribution in the colon, as it is over-expressed in the proximal and distal segments of the colon. Compared with normal mucosal tissue, there is high expression of endothelin receptor type A and low expression of endothelin receptor type B in colorectal cancer at all Dukes stages. By binding to endothelin receptor type A, endothelin-1 leads to down-regulation of epithelial and increased expression of mesenchymal markers. Also, endothelin-1 acts as anti-apoptotic factor through multiple pathways like PI3K-dependent AKT activation or NF-κB signaling. Members of the endothelin system might be used as cancer biomarker and from a therapeutic point of view, targeting the endothelin axis is a promising aim. In effect, potential drugs may include endothelin converting enzyme inhibitors as well as selective and non-selective antagonists of endothelin receptor types A and B. Biomedical Reviews 2014; 25: 1-13.