Chronic exposure to high fat diet exacerbates arsenic-induced lung damages in male mice: Possible role for oxidative stress

Arsenic is a common environmental and occupational contaminant worldwide which can influence the development of respiratory diseases. In recent years, alteration in the lifestyle as well as food habits have led to increased consumption of food containing high levels of fat. The present study was designed to evaluate the effects of chronic exposure to a high-fat diet (HFD) on arsenic-induced damages and oxidative stress in the lung tissue of mice. This is the first study to reveal the effect of diet-induced obesity on arsenic-induced lung damages. Seventy-two male Naval Medical Research Institute (NMRI) mice were divided into six groups and fed an HFD or standard diet (SD) while being exposed to 25 or 50 ppm of arsenic through drinking water for 20 weeks. At the end of the experiment, the lung weight to body weight ratio; oxidative stress markers, nitrite level, and hydroxyproline content in the lung tissue; and lung histology were evaluated. The results demonstrated that arsenic exposure leads to a significant decrease in the glutathione level and catalase enzyme activity, and significantly increased reactive oxygen species, malondialdehyde, and nitrite level, but it did not affect the superoxide dismutase activity and hydroxyproline content in the lung tissue. Consequently, all the parameters studied aggravated when HFD was consumed along with arsenic. These findings were confirmed by histological examination. Our study showed that HFD increased arsenic-induced lung damages through oxidative stress in mice. These findings could be important for clinical research to protect against arsenic-induced respiratory toxicity in humans

The Effects of the Toxicity of (Fe (so4).7H2o) on the isolated Mitochondria from the brain of rat

Introduction: Iron, through the reaction of Fenton, generates free radicals such as active oxygen radicals and activates the oxidative stress pathway. The oxidative stress due to the increased iron level in the brain regions plays  an important role in creation of neurodegenerative diseases. Methods and Results:In this study, the mitochondria of the brain tissue of Wild Wistar Rat isolated from various centrifuge rounds and with the concentrations of Fe (so4).7H2o were incubated at 30 and 60 minutes. To determine IC50 Fe (so4).7H2o, the mitochondrial survival ratio was measured by MTT test. Mitochondrial suspension with the concentration of 0.5 mg protein/ml at various concentrations of Fe (so4).7H2o was placed in a shaker incubator at 37° C for 30 and 60 minutes. Then the activity of mitochondrial complex 2 and the formation ratio of reactive oxygen species was investigated. The results showed that IC50 ratio for Fe (so4).7H2o was 20 and 5 μg/ml at 30 and 60 minutes, respectively, and mitochondria incubation isolated from the brain tissue of the rat with Fe (so4).7H2o can disrupt be the electron transfer chain and significantly increases the formation of reactive oxygen species compared to the control group (P <0.001). Conclusions:The findings of this study indicate that Fe (so4).7H2o disrupts electron transfer chain in the mitochondria and causes increasing ROS production. This excessive increase of ROS can activate the oxidative stress pathway and ultimately activate the cell toxicity pathways

Protective effect of metformin on toxicity of butyric acid and arsenic in isolated liver mitochondria and langerhans islets in male mice: an in vitro study

Objective(s): Arsenic, a toxic metal in drinking water and butyric acid (BA) is a free fatty acid found in many foods. These two can induce oxidative stress in some tissues. The present study investigated the protective effect of metformin against toxicity induced by Arsenic (As) and BA in isolated mice liver mitochondria and pancreatic islets. Materials and Methods: In this study, liver mitochondria were isolated by adopting different centrifugation methods and pancreatic islets isolated by a collagenase method. Mitochondria were incubated by BA (75 μM), As (100 μM) and metformin (0, 0.5, 1, 3, 10 mM) and the islets also incubated by BA (1000 μM), As (100 μM) and metformin (0, 1, 3, 10 mM) for 1 hr. At the end of study, mitochondrial viability (MTT), mitochondrial membrane potential (MMP), reactive oxygen species (ROS), malondial- dehyde (MDA), glutathione (GSH) and islets insulin secretion were measured employing specific relevant methods. Results: As and BA significantly increased ROS, MDA and ΔΨm levels and decreased GSH level, succinate dehydrogenase activity and insulin secretion. On the other hand, pretreatment with metformin, returned mitochondrial complex ІІ activity, reduced ROS, MDA and ΔΨm levels and increased GSH level and insulin secretion of pancreatic islets. Conclusion: As and BA in combination or in isolation induce oxidative stress in liver mitochondria and decrease insulin secretion of pancreatic islets. Metformin has a protective effect probably caused by its antioxidant feature. The findings suggest the potential role of metformin in mitochondria therapy and insulin secretion in many diseases

3-Bromopyruvate potentiates TRAIL-induced apoptosis in human colon cancer cells through a reactive oxygen species- and caspase-dependent mitochondrial pathway

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising anticancer cytokine with minimal toxicity towards normal cells. Nevertheless, most primary cancers are often intrinsically TRAIL-resistant or can acquire resistance after TRAIL therapy. This study aimed to investigate the inhibitory effect of co-treatment of 3-Bromopyruvate (3-BP) as a potent anticancer agent with TRAIL on colon cancer cells (HT-29). The results of present study indicated that combined treatment with 3-BP and TRAIL inhibited the proliferation of HT-29 cells to a greater extent (88.4%) compared with 3-BP (54%) or TRAIL (11%) treatment alone. In contrast, the combination of 3-BP and TRAIL had no significant inhibitory effect on the proliferation of normal cells (HEK-293) (8.4%). At a cellular mechanistic level, the present study showed that 3-BP sensitized human colon cancer cells to TRAIL-induced apoptosis via ROS generation, upregulation of Bax, downregulation of Bcl-2 and survivin, release of cytochrome c into the cytosol and activation of caspase3. In normal cells, 3-BP, TRAIL or combination of both had no significant effect on the ROS levels, release of cytochrome c and caspase3 activity. Therefore, the combination of 3-BP and TRAIL can be a promising therapeutic strategy for treatment of colon cancer.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author