Influence of copper(I) nicotinate complex on the Notch1 signaling pathway in triple negative breast cancer cell lines.

Triple negative breast cancer (TNBC) is a subtype of breast cancer which is characterized by its aggressiveness, poor and short overall survival. In this concept, there is a growing demand for metal-based compounds in TNBC therapy as copper complex that have a less toxic effect on normal cells and could stimulate apoptotic cell death. Additionally, Notch1 signaling pathway has received great attention as one of the most important potential targets for developing a novel therapeutic strategy. The present study is an attempt to assess the promising chemotherapeutic activities of copper(I) nicotinate (CNC) through its impact on the expression of downstream genes of Notch1 signaling pathway and the cell fate of TNBC. The co-treatment of TNBC cells with doxorubicin (Doxo) and CNC was also investigated. To approach the objective of the present study, TNBC cell lines; HCC1806 and MDAMB231, were utilized. MTT assay was used to determine the IC50 values of CNC and Doxo. After treatment, microtubule-associated protein light chain3 (LC3) were determined by flow cytometry. Additionally, qRT-PCR technique was used to detect the changes in genes levels that are involved Notch1 signaling pathway. Moreover, autophagosomes were monitored and imaged by Transmission electron microscopy. Treatment of TNBC cells with CNC modulated Notch1 signaling pathway in different manners with respect to the type of cells and the applied dose of CNC. The observed effects of CNC may reflect the possible anti-cancer activities of CNC in both types of TNBC. However, cell type and CNC dose should be considered.

Testicular oxidative damage and role of combined antioxidant supplementation in experimental diabetic rats.

The present study was designated to assess oxidative damage and its effect on germ cell apoptosis in testes of streptozotocin (STZ)-induced diabetic rats. The role of antioxidant supplementation with a mixture of vitamins E and C and alpha lipoic acid for protection against such damage was also evaluated. Forty-five adult male rats were randomly divided into three groups: group I, control, non-diabetic rats; group II, STZ-induced, untreated diabetic rats; group III, STZ-induced diabetic rats supplemented with a mixture of vitamins E and C and alpha lipoic acid. Glycated hemoglobin (HbA(1C)), glucose, and insulin levels were estimated in blood samples. Malondialdehyde (MDA), the activities of the enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and caspase-3 in addition to testosterone (T) level were all determined in testicular tissues. Histopathological studies using H&E stain, as well as, immunohistochemical detection of apoptosis using (TUNEL) method were also performed. Blood glucose and HbA(1c) were significantly increased while insulin was significantly decreased in STZ-induced diabetic rats as compared with controls. In rat testicular tissues, MDA, and caspase-3 activity were significantly elevated while SOD and GPx enzymatic activities as well as T level were significantly decreased in diabetic rats as compared with control group. Antioxidant supplementation to diabetic rats restored the testicular enzymatic activities of SOD and GPx to almost control levels, in addition, MDA and caspase-3 activity decrease while T increase significantly as compared with untreated diabetic group. Prominent reduction of germ cell apoptosis was found in diabetic rats supplemented with antioxidants. An important role of testicular oxidative damage and germ cell apoptosis in diabetes-induced infertility could be suggested, treatment with antioxidants has a protective effect by restoring SOD and GPx antioxidant enzymatic activity.

Diazinon toxicity affects histophysiological and biochemical parameters in rabbits.

Diazinon is a widely used pesticide in agriculture. So, the current work aimed to investigate the effects of diazinon exposure on some physiological and biochemical parameters, as well as, histopathological changes and histochemical acetyl-cholinesterase activity (AChE). The red Baladi rabbits were dipped into water (Control Group), diazinon at low concentrations of 0.6 mg diazinon low concentration (DLC) or high concentration of 3mg diazinon high concentration (DHC) dissolved in 1l of water for 10s. Treatment was repeated after 10 days and animals were sacrificed between 0 and 21 days after the second treatment. Blood analysis revealed that Red blood cells (RBC's), hemoglobin (Hb) and plasma total protein (TP) were significantly decreased in both diazinon concentrations (P<0.01), (P<0.05), (P<0.01) respectively. Cholesterol and microsomal protein were increased (P<0.01), while, liver/ body weight and cytochrome P-450 were decreased in both concentrations (P<0.01). Also there was a highly significant effect of concentration X day interaction on all parameters (P<0.01). Histopathological changes of liver, kidney and brain were observed after DHC dipping. Glycogen content was decreased in liver and increased in kidney Bowman's capsule. Furthermore, AChE activity was inhibited in brain tissue, decreased in liver cells, but gradually increased in kidney glomerular cells. Therefore, kidney and brain were highly affected by diazinon exposure compared with the liver. Exposure of animals to diazinon caused extensive changes in physiological, biochemical, and histopathological parameters as well as histochemical AChE. So, contact exposure of diazinon leads to negative response on animal health.

Efficacy of praziquantel against Giardia lamblia in rats: parasitological, pathological and therapeutic study.

Rats were divided into two experimental groups received single or split doses of PZQ, and two control groups one infected untreated and the other normal healthy rats. The effect of infection on rat growth, on jejunal and duodenal architecture were studied histopathologically after H&E staining. The jejunal ultrastructure was examined by SEM and TEM. The effect of PZQ was evaluated using the same techniques. It was observed that infected as well as infected treated animals gained less weight than healthy control. Intensity of infection decreased gradually after treatment. Cure rate was 100% after split dose and 80% after a single dose. Altered villus height and cryptic depth were the characteristic changes in the architecture of the duodenum and jejunum, more pronounced in the latter. Split dose of PZQ revealed more improvement of the histopathological findings than a single dose. By SEM, circular imprints representing defects in the villi were observed in the jejunum. By TEM deformation of microvillar architecture was observed together with organellar changes in the RER and the mitochondria, after PZQ treatment.