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

Nephroprotective Effect of Hydroalcoholic Extract Allium jesdianum Boiss against Carbon Tetrachloride Induced Nephrotoxicity via Stress Oxidative in Mice

Background: Nephrotoxicity is one of the most common renal problems that especially occur when the body is exposed to drugs or chemical reagents. Allium jesdianum Boiss is the largest and most important plants genus of onion family that possesses many pharmacological effects. The present study was undertaken to investigate the effect Allium jesdianum Boiss in the treatment of nephrotoxicity induced by carbon tetrachloride (CCl4). Methods: Forty two male mice were randomly divided into six groups; control, sham, CCl4 (1 ml/Kg, i.p) single dose, Allium (500, 1000 and 2000 mg/kg) + CCl4. Blood urea nitrogen (BUN) and serum creatinine (Cr) evaluated in serum. Glutathione (GSH), catalase (CAT), malondialdehyde (MDA) and reactive oxygen species (ROS) were analyzed in kidney tissue homogenate and done the microscopic studies of renal tissue. Results: The results indicated a significant increase of serum BUN and Cr as well as MDA and ROS levels and decrease of GSH and CAT in CCl4 treated mice when compared with the control group (p < 0.001), whereas all studied endpoints were significantly altered in pretreatment with Allium extract when compared with CCl4 treated mice (p < 0.001). Renal histopathology indicated normal appearances reduced in CCl4 treated mice and Allium extract administration improved changes in renal tissue. Conclusion: Administration of the hydroalcoholic extract of Allium jesdianum Boiss could prevent nephrotoxicity induced by CCl4. The protective potential may involve the powerful antioxidant of this plant by eliminating free radicals induced by CCl4

Protective Effect of Gemfibrozil on Hepatotoxicity Induced by Acetaminophen in Mice: the Importance of Oxidative Stress Suppression

Purpose: Gemfibrozil (GEM) apart from agonist activity at peroxisome proliferator-activated receptor-alpha (PPAR-α) has antioxidant and anti-inflammatory properties. Accordingly, the present study was designed to investigate the protective effect of GEM on acute liver toxicity induced by acetaminophen (APAP) in mice. Methods: In this study, mice divided in seven groups include, control group, APAP group, GEM group, three APAP groups pretreated with GEM at the doses of 25, 50 and 100 mg/kg respectively and APAP group pretreated with N-Acetyl cysteine. GEM, NAC or vehicle were administered for 10 days. In last day, GEM and NAC were gavaged 1 h before and 1 h after APAP injection. Twenty four hours after APAP, mice were sacrificed. Serum parameters include alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver tissue markers including catalase enzyme activity, reactive oxygen species (ROS), malondialdehyde and reduced glutathione (GSH) levels determined and histopathological parameters measured. Results: GEM led to significant decrease in serum ALT and AST activities and increase in catalase activity and hepatic GSH level and reduces malondialdehyde and ROS levels in the liver tissue. In confirmation, histopathological findings revealed that GEM decrease degeneration, vacuolation and necrosis of hepatocytes and infiltration of inflammatory cells. Conclusion: Present data demonstrated that GEM has antioxidant properties and can protect the liver from APAP toxicity, just in the same pathway that toxicity occurs by toxic ROS and that GEM may be an alternative therapeutic agent to NAC in APAP toxicity

Prevalence of Symptoms in Patients Poisoned with Iranian Crack in Ahvaz Razi Hospital in 2008-2013

Background: Crack is a strong and smoking form of cocaine, but Iranian crack is different from common crack cocaine, having symptoms and side effects similar to those of heroin. This study was to investigate the prevalence and clinical symptoms in patients poisoned with Iranian crack poisoning hospitalized in Ahvaz Razi Hospital in the years 2008-2013. Methods: In this study, 63 subjects with Iranian crack poisoning referred to the poisonings center of Ahvaz Razi Hospital, Khuzestan Province, Iran, between 2008 and 2013. The information collected from their records based on hospital data includes reference data, demographic data, prevalence and clinical symptoms and treatment. Results: Of 63 subjects, 88.9% were male. The mean age of the subjects was 25 years. The majority of the subjects were single. Most of them used another substance along with Iranian crack. The first clinical symptoms of more than half of them were loss of consciousness. 54% of them needed antidote; 69.8% admitted to ICU. 6.3% of the subjects died. Conclusion:We concluded that the most prevalent pattern and the first signs of Iranian crack overdose are similar to heroin consumption and not crack cocaine. Therefore, more studies are required for clinical management of acute or chronic toxicity of this illicit drug and to reduce further damages

Histopathological and Biomedical Parameters Determination in the Protective Effect of Hydroalcoholic Extract of Allium Jesdianum on Hepatotoxicity Induced by Bromobenzene: Effect of Allium Jesdianum Extract on Bromobenzene Induced Hepatotoxicity

Allium Jesdianum (AJ) is the native plant mostly grown in Middle East region that has the excellent pharmacological properties. In this study, we evaluated the hepatoprotective effect of hydroalcoholic extract of AJ on liver injury induced by Bromobenzene (BB) in male mice. Animals were randomly divided into five groups, control group received normal saline plus olive oil, groups 2-4 received (500, 1000 and 2000 mg/kg) AJ extract plus BB for 5 days and 5th group received BB (460 mg/kg). On the fifth day all groups received hexobarbital sodium (25 mg/kg, i.p). It should be noted that sleeping time of the all mice were recorded. After 24 hours the mice were sacrificed. By serum and tissue biomarkers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), reduced glutathione (GSH), malondialdehyde (MDA), and histopathological studies were measured. The results showed that BB significantly increased sleeping time, ALT, AST, and MDA levels besides and decreased GSH level compared with the control group. AJ extract at doses1000and 2000 mg/kg showed a significant alter in all studied endpoints and dose 2000 mg/kg showed a marked improvement in histopathological examination. The present finding indicated that administration of the hydroalcoholic extract of AJ could prevent hepatotoxicity induced by BB via improvement serum and tissue parameters and histopathological alterations in liver tissue

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