Therapeutic effect of dithiophenolato chitosan nanocomposites against carbon tetrachloride-induced hepatotoxicity in rats.

Our previous study showed that dithiophenolate (DTP) and its chitosan nanoparticles (DTP-CSNPs) have abilities to bind with DNA helixes. So in this study, their lethal doses (LD50) and therapeutic roles against rat liver injuries induced by carbon tetrachloride (CCl4) were evaluated. The study focused on the determination of the markers of oxidative stress (OS) and apoptosis and compare the results with those of cisplatin treatment. The results revealed that LD50 values of DTP and DTP-CSNPs are 2187.5 and 1462.5 mg/kg, respectively. Treatment with DPT and DPT-CSNPs after CCl4 administration reduced liver injuries, induced by CCl4, and improved liver functions and architecture through the reduction of OS and apoptosis. Where the oxidant marker was decreased with elevations of antioxidant markers. Also, there was an elevation in Bcl-2 value, with decreases in caspase-8, Bax, and Bax/Bcl-2 ratio. DPT-CSNPs treatment gave preferable results than those treated with DPT. Moreover, DTP and DPT-CSNPs treatment gave better results than cisplatin treatment. The administration of healthy rats with low doses of DTP and DTP-CSNPs for 14 days had no effect. Otherwise, the study on HepG2 cell line showed that DTP and DPT-CSNPs inhibited cell growth by arresting cells in the G2/M phase and inducing cell death. In conclusion, DTP and DTP-CSNPs have antiapoptotic and anti-oxidative stress toward hepatotoxicity induced by CCl4. Moreover, DTP and DTP-CSNPs have anticancer activity against the HepG2 cell line. Generally, DTP-CSNPs are more effective than DTP. So, they can be used in the pharmacological fields, especially DTP-CSNPs.

Protective Effect of Natural Antioxidant, Curcumin Nanoparticles, and Zinc Oxide Nanoparticles against Type 2 Diabetes-Promoted Hippocampal Neurotoxicity in Rats.

Numerous epidemiological findings have repeatedly established associations between Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease. Targeting different pathways in the brain with T2DM-therapy offers a novel and appealing strategy to treat diabetes-related neuronal alterations. Therefore, here we investigated the capability of a natural compound, curcumin nanoparticle (CurNP), and a biomedical metal, zinc oxide nanoparticle (ZnONP), to alleviate hippocampal modifications in T2DM-induced rats. The diabetes model was induced in male Wistar rats by feeding a high-fat diet (HFD) for eight weeks followed by intraperitoneal injection of streptozotocin (STZ). Then model groups were treated orally with curcumin, zinc sulfate, two doses of CurNP and ZnONP, as well as metformin, for six weeks. HFD/STZ-induced rats exhibited numerous biochemical and molecular changes besides behavioral impairment. Compared with model rats, CurNP and ZnONP boosted learning and memory function, improved redox and inflammation status, lowered Bax, and upregulated Bcl2 expressions in the hippocampus. In addition, the phosphorylation level of the MAPK/ERK pathway was downregulated significantly. The expression of amyloidogenic-related genes and amyloid-beta accumulation, along with tau hyperphosphorylation, were lessened considerably. In addition, both nanoparticles significantly improved histological lesions in the hippocampus. Based on our findings, CurNP and ZnONP appear to be potential neuroprotective agents to mitigate diabetic complications-associated hippocampal toxicity.

A Titanium (IV)-Dithiophenolate Complex and Its Chitosan Nanocomposite: Their Roles towards Rat Liver Injuries In Vivo and against Human Liver Cancer Cell Lines.

Titanium (IV)-dithiophenolate complex chitosan nanocomposites (DBT-CSNPs) are featured by their antibacterial activities, cytotoxicity, and capacity to bind with DNA helixes. In this study, their therapeutic effects against rat liver damage induced by carbon tetrachloride (CCl4) and their anti-proliferative activity against human liver cancer (HepG2) cell lines were determined. Results of treatment were compared with cisplatin treatment. Markers of apoptosis, oxidative stress, liver functions, and liver histopathology were determined. The results showed that DBT-CSNPs and DBT treatments abolished liver damage induced by CCl4 and improved liver architecture and functions. DNA fragmentation, Bax, and caspase-8 were reduced, but Bcl-2 and the Bcl-2/Bax ratios were increased. However, there was a non-significant change in the oxidative stress markers. DBT-CSNPs and DBT inhibited the proliferation of HepG2 cells by arresting cells in the G2/M phase and inducing cell death. DBT-CSNPs were more efficient than DBT. Low doses of DBT and DBT-CSNPs applied to healthy rats for 14 days had no adverse effect. DBT and DBT-CSNP treatment gave preferable results than the treatment with cisplatin. In conclusion, DBT-CSNPs and DBT have anti-apoptotic activities against liver injuries and have anti-neoplastic impacts. DBT-CSNPs are more efficient. Both compounds can be used in pharmacological fields.

Ameliorative effect of curcumin and zinc oxide nanoparticles on multiple mechanisms in obese rats with induced type 2 diabetes.

The present study was carried out to investigate the therapeutic effect of synthesized naturally compounds, curcumin nanoparticles (CurNPs) and metal oxide, zinc oxide nanoparticles (ZnONPs) on a high-fat diet (HFD)/streptozotocin (STZ)-induced hepatic and pancreatic pathophysiology in type 2 diabetes mellitus (T2DM) via measuring AKT pathway and MAPK pathway. T2DM rats were intraperitoneally injected with a low dose of 35 mg/kg STZ after being fed by HFD for 8 weeks. Then the rats have orally received treatments for 6 weeks. HFD/STZ-induced hepatic inflammation, reflected by increased phosphorylation of p38-MAPK pathway's molecules, was significantly decreased after nanoparticle supplementation. In addition, both nanoparticles significantly alleviated the decreased phosphorylation of AKT pathway. Further, administration of ZnONPs, CurNPs, conventional curcumin, and ZnSO4 (zinc sulfate), as well as metformin, effectively counteracted diabetes-induced oxidative stress and inflammation in the internal hepatic and pancreatic tissues. Based on the results of the current study, ZnONPs and CurNPs could be explored as a therapeutic adjuvant against complications associated with T2DM. Both nanoparticles could effectively delay the progression of several complications by activating AKT pathway and down-regulating MAPK pathway. Our findings may provide an experimental basis for the application of nanoparticles in the treatment of T2DM with low toxicity.

New stains for anterior capsule surgery.

PURPOSE: To investigate whether new dyes and dye combinations can give equivalent or better staining in anterior capsule surgery than existing dyes with a low degree of toxicity on relevant cells. SETTING: University laboratory of Jacobs University Bremen, Germany. DESIGN: Laboratory experimental study. METHODS: Pig eyes were collected post mortem. Cataract was induced by microwave irradiation. Access to the lens capsule was through open-sky surgery. Staining was performed and results were documented by photography. The toxicity of the dyes was evaluated in 3 different cell lines immediately after exposure and with a delay of 24 hours, with exposure in the dark or subsequent strong illumination. RESULTS: A new cyanine dye, BIP (2-[5-[3,3-dimethyl-1-(4-sulfobutyl)-1,3-dihydro-indol-2-ylidene]-penta-1,3-dienyl]-3,3-dimethyl-1-(4-sulfobutyl)-3H-indolium sodium), was found to lead to green staining, with reduced toxicity on corneal endothelial cells. Staining could be further enhanced by combining it with trypan blue. Methylene blue was very toxic, whereas its combination with trypan blue was much less toxic. CONCLUSIONS: With BIP alone or in combination with trypan blue, safe staining of the capsule can be achieved, resulting in a green color.

Postpartum depression symptoms among Syrian refugee women living in Jordan.

Postpartum depression (PPD) is recognized as a common maternal health problem, but few studies have investigated the postpartum mental health of refugee women. In this cross-sectional study, we investigated the prevalence of PPD symptoms and associated factors among Syrian refugee women living in north Jordan. Women (N = 365) were recruited from four health care centers in Ramtha and Jarash, cities in northern Jordan. Participants completed a demographic data form, the Edinburgh Postnatal Depression Scale (EPDS), and the Maternal Social Support Scale at 6-8 weeks postpartum. Half (49.6%; n = 181) of the Syrian refugee women scored >12 on the EPDS. PPD symptoms were significantly associated with low social support, low monthly income, and recent immigration (less than 2 years). There is a high level of PPD symptoms among Syrian refugee women, many of whom are living in poverty and with limited social support. The results highlight the need for immediate action by governments to support childbearing refugee women with early screening for psychosocial risk and respond to women's physical and mental health, and social needs through interservice collaboration. Social support programs would meet an important need for these women, as would ongoing assessment by health professionals and early intervention for women who screen positive for PPD.

Toxicity and phototoxicity in human ARPE-19 retinal pigment epithelium cells of dyes commonly used in retinal surgery.

PURPOSE: To compare, for the first time, systematically the toxicity and phototoxicity of dyes and dye combinations used in vitreoretinal surgery. The dyes were trypan blue, brilliant blue G, trypan blue + brilliant blue G, indocyanine green, bromophenol blue, bromophenol blue + brilliant blue G, and acid violet 17, in clinically used concentrations. METHODS: Human ARPE retinal pigment epithelium cells were exposed to the dyes for 30 min. For phototoxicity, the cells were exposed for 15 min to high-intensity light from a light emitting diode source with an intensity similar to surgical conditions. Toxicity was assayed either directly after exposure to either dye alone or dye and light, or with a delay of 24 h. RESULTS: None of the dyes or their combinations was toxic when cells were exposed to them at ambient light. Acid violet led to a reduction viability by 90% already immediately after light exposure. Bromophenol blue and its combination with brilliant blue G showed strong phototoxicity (reduction of viability by 83%) when assayed with delay. Indocyanine green with different agents to adjust osmolarity (balanced salt solution, glucose, and mannitol) was not found to be toxic. CONCLUSION: The strong immediate phototoxicity of acid violet reflects its clinical toxicity. Bromophenol blue might also be disadvantageous for patient outcome because of its delayed phototoxicity. The other dyes (trypan blue, brilliant blue g, and indocyanine green) were not found to be toxic neither with exposure to ambient light nor after exposure to light of intensities used in surgery.

Combination between Taxol-Encapsulated Liposomes and Eruca sativa Seed Extract Suppresses Mammary Tumors in Female Rats Induced by 7,12 Dimethylbenz(α)anthracene.

Taxol (paclitaxel) is a powerful anti-cancer drug widely used against several types of malignant tumors. Because Taxol may exert several side effects, a variety of formulations have been developed. One of these features liposomes, regarded as one of the most promising drug carriers, biocompatible and best able to reduce drug toxicity without changing efficacy against tumor cells. Eruca sativa seed extract (SE) is considered a promising natural product from cruciferous vegetables against breast cancer, increasing chemotherapeutic and eliminating harmful side effects. The effects of Taxol-encapsulated liposomes (T) alone and in combination between Eruca sativa seed extract on nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels were investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(α) anthracene (DMBA) using qRT-PCR. The results showed that DMBA increased NF-κB, COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while decreasing glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. T and T-SE treatment reduced NF-κB, COX-2 and Bcl-2 gene expression levels and LP. Hence, T and T-SE treatment appeared to reduce inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC.

Inhibition of NF-κB, Bcl-2 and COX-2 Gene Expression by an Extract of Eruca sativa Seeds during Rat Mammary Gland Carcinogenesis.

The effect of Eruca sativa seed extract (SE) on nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels was investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(α)anthracene (DMBA). DMBA increased NF-κB, COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while, decreased glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. After DMBA administration, SE treatment reduced NF-κB, COX-2 and Bcl-2 gene expression levels and LP. Hence, SE treatment reduced inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC. Analysis revealed that SE has high concentrations of total flavonoids, triterpenoids, alkaloids and polyphenolic compounds such as gallic, chlorogenic, caffeic, 3,4-dicaffeoyl quinic, 3,5-dicaffeoyl quinic, tannic, cinnamic acids, catechin and phloridzin. These findings indicate that SE may be considered a promising natural product from cruciferous vegetables against breast cancer, especially given its high antioxidant properties.

Halogenated Dodecaborate Clusters as Agents to Trigger Release of Liposomal Contents.

Halogenated dodecaborates, and especially dodecaiodododecaborate(2-), are found to trigger effectively the release of the contents of phospholipid liposomes, including liposomes containing distearoylphosphatidylcholine and cholesterol, which are used clinically in cancer therapy. The basis of the release is studied through differential scanning calorimetry, cryo-transmission electron microscopy, and atomic force microscopy. Upon administration at high concentrations, drastic morphological changes are induced by the dodecaborates. Their possible use in triggered release is suggested.