Anticancer potency of Egyptian venom snakes on MCF-7 and HepG2 carcinoma cells.

Breast and hepatic cancers are the leading incidences in the globe occurring of the human sufferings from various cancers. Snake venoms have been reported to provide effective therapeutic agents. The current study investigates the anticancer potency of Egyptian venoms snakes on two cells: breast cancer cells (MCF-7) and hepato-cancer cells (HepG2) (In vitro assay). The examined venoms were more potent on MCF-7 than HepG2 cells. Their inhibition % on MCF-7 ranged from 71.47 to 99.02% with medium inhibition concentrations (IC50s): 3.48, 3.60, 3.70, 4.33, and 4.49 µg/ml for venoms: Echis pyramid (E.H), Cerastes vipera (C.V), Naja haje (N.H), Echis coloratus (E.C), and Cerastes cerastes (C.C), respectively. The values of IC50s on HepG2 were 4.32, 17.77, 59.72, 63.75, and 217.90 µg/ml for toxins: E.C, E.P, C.V, C.C, and N.H, respectively. Some biomarkers were conducted to investigate the apoptotic effects of toxins into the cells. Increasing profiles of lactate dehydrogenase (LDH) activity and levels of glutathione content (GSH) and malodialdhyde (MDA) as well as repairment of DNA indicated such these actions. So, more reliable investigations on these venoms were needed to provide intelligent therapeutic agent for cancer treatment.

Tissue distribution, placental transfer and excretion of silver nanoparticles in pregnant rats after a single oral dose.

A quantitative assessment of silver nanoparticles (AgNPs) in fluids and some organs of pregnant rats as well as their fetal blood were carried out in this study. A single oral dose (1mg/kg) of AgNPs with a size range of 4-20 nm was administered to pregnant rats on the 19th of gestation. Five groups were euthanized after 10 min, 1, 6, 12, and 24 hr as well as the control group. Total Silver (Ag) contents were measured in bloods (maternal and fetal) and several organs using Inductive Coupled Plasma Optical Emission Spectroscopy (ICP-OES) followed by acid digestion. In maternal blood, AgNPs were found to increase time-dependently after 12 and 24 hr into 0.135 and 0.224 µg/ml, but it was slightly higher in fetal blood (0.32 and 0.31 µg/ml) after 10 min and 1 hr. In other samples: kidneys, liver, spleen, placenta, and uterus the data indicated that NPs were rapidly absorbed from the dosing site (gastrointestinal tract) as evidenced by the detection of Ag in the analyzed samples (fluids and tissues). On the other hand, the cumulative percentages of excretion level in urine was 8.25% which was higher than in feces (4.77%) after 24 hr. These findings indicate the ability of AgNPs to accumulate in pregnant rats and transfer to their fetus imposing adverse outcomes and male formation. Thus, further investigations must be followed for direct and/or indirect exposure to such NPs before decision for their practices.

Tissue Distribution, Pharmacokinetics, and Effect of Hematological and Biochemical Parameters of Acute Intravenous Administration of Silver Nanoparticles in Rats.

The widespread biomedical and commercial applications of silver nanoparticles (AgNPs) have increased their potential for human and environmental exposure and toxicity to human health. The bio-distribution and toxicity of AgNPs in rodents following inhalation, intratracheal instillation, and oral ingestion are well documented; however, little is known about the bio-distribution of intravenously (IV)-administered AgNPs and their organ-specific pathophysiological effects. Here, we investigate the pharmacokinetic pattern and tissue distribution of AgNPs in male rats following IV administration. The animals were humanely sacrificed after 10 min, 1 h, 6 h, 12 h, 24 h, and 168 h of AgNP administration, and the silver (Ag) content was measured from blood samples and various tissues following acid digestion. The AgNPs were readily absorbed and subsequently distributed into most organs predominantly in the colon, small intestine, kidney, and heart after 6 h; however, they were the highest in the spinal cord after 168 h. White blood cells (WBCs) were significantly increased (42-60%) in AgNP-administered animals at all time points except 10 min. Regarding platelets, all AgNP-administered animals showed counts 7.8-39.2% lower, with the lowest count at 168 h post-administration. In the case of lymphocytes (LYMs), the AgNP-treated animals exhibited a count 19.5-41% lower at 10 min and 1 h post-administration; however, the animals at 168 h post-administration showed a count 30.5% more. The mean corpuscular hemoglobin (MCH) counts from the AgNP-treated animals were decreased by 50-62%. The concentrations of aspartate transaminase (AST), urea, and creatinine were increased in the AgNP-treated animals. Taken together, the results suggest that the acute IV administration of AgNPs alters metabolic and hematological parameters in animals and may pose a health risk to humans.

Apoptotic and histopathological defects enhanced by titanium dioxide nanoparticles in male mice after short-term exposure.

Titanium dioxide nanoparticles (TiO2NPs) are commercially utilized in diverse fields. Therefore, the current study investigated the apoptotic and histopathological defects that were caused in male mice following intraperitoneal (i.p) injection of TiO2NPs for 28 days. Doses: 2.5, 5.0, 10.0 and 20.0 mg/kg body weight were applied (10 mice for each group). Results revealed that, lactate dehydrogenase (LDH) activity was significantly increased in homogenates of liver, spleen, kidney, lung, heart, and muscles of treated animals, respect to their controls. Also, significant alterations in acid and alkaline phosphatase (ACP and ALP) activities were reported. The dose 5.0 mg/kg exhibited a significant decline in cell viability of blood samples (74.9 %) (P 0.05 = 0.0177), followed by 2.5 mg/kg (80.8 %), and finally the 10.0 mg/kg (81.8 %) with respect to control (96.3 %). Additionally, significant increases of expressed proteins of caspases-3 and-7 were noticed in cells of the treated animals. Ultrastructural investigations in sections of liver, kidney, lung and spleen of the treated animals showed significant defects, especially in the nucleus, mitochondria and rough endoplasmic reticulum (RER), compared to normal patterns of the control. Also, significant induction of nanoparticle (NPs)-phagolysosomes was visualized in sections of the treated animals. The present findings might provide evidence for the risk pattern of TiO2NPs in mammals after short-term exposure. So, TiO2NPs-based commercial products have now increased in the markets, and it is prudent to investigate their mammalian toxicology.

Histopathological alterations induced by marine environmental pollutants on the bivalve Cerastoderma glaucum (Bruguière 1789) from Temsah Lake, Suez Canal, Egypt.

Bivalves are considered a main consumed matrix for coastal communities worldwide and classified as hyperaccumulators of pollutants. The present study aims to determine some micro-organisms, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and okadaic acid (OA) levels in Cerastoderma glaucum collected from Temsah Lake, Egypt, and their induction through histopathological damage and caspase-3 protein expression. During the autumn, it was found different types of biological and chemical pollutants, especially benzo[a]pyrene (BaP) that accumulated in C. glaucum soft tissues and exceeded the safety limit for shellfish consumption. Dioxin-like PCB3 was predominant in C. glaucum soft tissues during autumn, but the total levels of PCBs in these tissues have not exceeded the permissible limit. Chlorophyll-a (Chl. a), nutrient concentrations, and Prorocentrum lima dinoflagellates in the water significantly increased during autumn. High P. lima abundance was confirmed by high OA in the soft tissues during this season compared to the other seasons. The measured contaminants may render C. glaucum more susceptible to bacterial and fungal infections. The autumn season showed a significant increase in the colony-forming units (CFU). C. glaucum showed calcification abnormalities and adhering of abnormal brown organic material to the inner surface of the shell valves, which was related to poor water conditions and Vibrio infection. Damages or injuries on gills and digestive gland tissues indicated an impact of the pollutants on C. glaucum. Also, high expressions of caspase-3 were recorded in these tissues during all the seasons. So, C. glaucum cockles, collected from Temsah Lake, may induce serious diseases to consumers, especially when eaten raw or insufficient cooking.

Mitochondrial biochemical and histopathological defects induced by the herbicide pendimethalin in tilapia fish (Oreochromis niloticus).

The mitochondrial defects were evaluated after administering tilapia fish, Oreochromis niloticus to sublethal doses (1.02 and 5.10 mg kg-1) of the herbicide pendimethalin (PD). All treatments exhibited a decrease in the cytochrome contents of gills, liver, and brain samples after 12, 24, and 48 h compared with the untreated individuals. However, malondialdehyde (MDA) levels were significantly increased in gills and liver samples. Also, the histopathological profiles showed significant swelling in mitochondria and intracellular spaces in cytoplasm of gills samples. The mitochondrial defects in the treated fish showed a slight decline in cytoplasm/mitochondria ratio (0.92-fold) compared to the control. In hepato-sections of treated fish, destructed mitochondria with less dense matrix as well as some vacuolated mitochondria with matrix disoriented cristae were noted. Similar patterns were observed in brain sections, where destructed axons and a significant decline in cytoplasm/mitochondria ratio (0.52-fold) were found. Therefore, the use of mitochondrial defects and histopathological alterations might represent good markers to assess the impact of herbicides on aquatic organisms. Moreover, the disorganization of cell components is considered an important sign of organ dysfunction.

Cytotoxicity and Oxidative Stress Responses of Imidacloprid and Glyphosate in Human Prostate Epithelial WPM-Y.1 Cell Line.

Insecticide imidacloprid and herbicide glyphosate have a broad spectrum of applicable use in the agricultural sector of Egypt. Their ability to induce in vitro cytotoxic and oxidative stress on normal human cells (prostate epithelial WPM-Y.1 cell line) was evaluated with the methyl tetrazolium test (MTT) and histopathological investigation. Cell viability was evaluated with an MTT test for 24 h. The median inhibition concentration (IC50) values were 0.023 and 0.025 mM for imidacloprid and glyphosate, respectively. Sublethal concentrations: 1/10 and 1/50 of IC50 and IC50 levels significantly induced an increase in the lactate dehydrogenase (LDH) activity and malondialdehyde (MDA) level compared with the untreated cells. Rapid decrease in the glutathione (GSH) content and glutathione-S-transferase (GST) activity was induced. Significant increases were recorded in activities of catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), respectively, compared with the control group. Transmission electron microscopic (TEM) investigation showed significant defects in the cells following pesticide treatments for 24 h. Therefore, it is concluded that imidacloprid and glyphosate are very toxic in vitro assays and able to induce apoptotic effects as well as oxidative stress. So, these findings provide a scenario of multibiomarkers to achieve the imposed risks of pesticides at low doses.

In vivo evaluation of oxidative stress and biochemical alteration as biomarkers in glass clover snail, Monacha cartusiana exposed to zinc oxide nanoparticles.

Oxidative stress is considered a main commonly reported mechanism of nanoparticles toxicity, so this study aimed to evaluate oxidative stress and biochemical alterations in the haemolymph and digestive gland of snail, Monacha cartusiana exposed to sublethal concentrations of zinc oxide nanoparticles (ZnONPs) for 14 days (d). The results indicated that, ZnONPs induced significant increases in lipid peroxidation (LPO) and lactate dehydrogenase (LDH) in treated animals and did not return to normal levels after recover period. A significant decline of glutathione peroxidase (GPx), glutathione-S-transferase (GST) activities, and glutathione (GSH) content in the haemolymph and digestive gland of snails was observed when compared with control. A significant increase was observed in catalase (CAT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities of treated animals. In general, nano-materials are able to induce oxidative stress in exposed animals. The present findings indicate that, alterations of antioxidant enzyme activities, increase of LPO, LDH, and reducing of GSH content and GST, GPx activities are recognized to oxidative stress and cell damage. This species could be considered a good bioindicator to assess nano-materials exposure.