Protective Effect of Ozone against Hemiscorpius lepturus Envenomation in Mice / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Scorpion (Hemiscorpius lepturus) stings are a public health concern in Iran, particularly in south and southwestern regions of Iran. The gold standard for the treatment of a scorpion sting is anti-venom therapy. However, immunotherapy can have serious side effects, such as anaphylactic shock (which can sometimes even lead to death). The aim of the current study was to demonstrate the protective effect of ozone against toxicity induced by Hemiscorpius lepturus (H. lepturus) venom in mice.</p><p><b>METHODS</b>Eight hours after the injection of ozone to the experimental design groups, the male mice were decapitated and mitochondria were isolated from five different tissues (liver, kidney, heart, brain, and spinal cord) using differential ultracentrifugation. Then, assessment of mitochondrial parameters including mitochondrial reactive oxidative species (ROS) production, mitochondrial membrane potential (MMP), ATP level, and the release of cytochrome c from the mitochondria was performed.</p><p><b>RESULTS</b>Our results showed that H. lepturus venom-induced oxidative stress is related to ROS production and MMP collapse, which is correlated with cytochrome c release and ATP depletion, indicating the predisposition to the cell death signaling.</p><p><b>CONCLUSION</b>In general, ozone therapy in moderate dose can be considered as clinically effective for the treatment of H. lepturus sting as a protective and antioxidant agent.</p>

Therapeutic implication of coenzyme Q10 during statin therapy: pros and cons

Coenzyme Q10 [CoQ10] is a vitamin-like substance, and a natural intermediate of electron transport chain [ETC] of mitochondria which can accepts and donates electrons from complex I to complex II. CoQ10 shares a biosynthetic pathway with cholesterol, therefore it can be a potential target of the widely available lipid-lowering agents. The lipid lowering drugs such as statins, are widely administered to individuals who have high cholesterol levels and potential risk for cardiovascular diseases. Statins do not cause serious adverse effects in human however its long-term administration can cause a variety of myopatic complaints.This article reviews the a] clinical benefits of CoQ10 b] association between administration of statin and CoQ10 deficiency and c] involvement of CoQ10 in statin-associated myopathy

review of nitrate and nitrite toxicity in foods

Agricultural advancement and population growth have prompted increases in food supplies, and higher crop yields have been made possible through the application of fertilizers. Large quantities of livestock and poultry on farms, along with the accumulation of biomass and agricultural residues, can cause contamination of ground water resources and other water sanitation concerns in both developing and developed countries. Nitrate is mainly used as a fertilizer in agriculture, and because of its high solubility in water, it can create biological problems in the environment. High usage of nitrite in the food industry as a preservative, flavor enhancer, antioxidant, and color stabilizing agent can cause human exposure to this toxic compound. Nitrite is 10 times as toxic as nitrate in humans. Nitrate is converted to nitrite and nitrosamine compounds in the human stomach, which can lead to bladder cancer. In this review, sources of nitrate and nitrite exposure were investigated. Furthermore, the review evaluates standard levels of nitrate and nitrite in different foods, and acceptable daily doses of these compounds in various countries. Finally, we discuss valid methods of nitrate and nitrite identification and removal in foods

comparison of toxicity mechanisms of cigarette smoke on isolated mitochondria obtained from rat liver and skin

Previous studies demonstrated that CSE induces oxidative stress and its consequences on isolated mitochondria obtained from lung, heart and brain which may provide insight into the role of CSE in human health and disease. The present study was carried out to further characterize and compare toxic effect of CSE extract on isolated mitochondria obtained from either a directly contacting tissue [i.e. skin] or a vital visceral tissue [i.e. liver].We obtained Rat liver and skin mitochondria by differential ultracentrifugation and incubated the isolated mitochondria with different concentrations [1, 10 and 100%] ofstandardizedcigarette smoke extract [CSE]. Our results were similar to our previous study which discovered CSE toxicity mechanisms on isolated mitochondria obtained from lung, heart and brain with minor changes.CSE induced a significant rise in ROS formation, lipid peroxidation and mitochondrial membrane potential collapse and mitochondrial swelling on isolated mitochondria obtained from both liver and skin. CSE induced Decrease in ATP concentration on isolated mitochondria obtained from both liver and skin did not include CSE lowest concentration [1%]. Our findingsshowed that CSE-induced toxicity in liver and skin is due to disruptive effect on mitochondrial respiratory chain which canleads to cytochrome c release and apoptosis signaling

Toxicity mechanisms of cigarette smoke on mouse fetus mitochondria

Maternal smoking has been recognized as a common cause of low birth weight, preterm birth and the decrease of gestational age period. Unfortunately, there is an increasing interest within public especially woman in Iran in the tobacco products consumption. On the other hand, the deleterious effect of maternal smoking on human fetus in pregnancy period especially in the first trimester encouraged us to investigate toxicity mechanisms of cigarette smoke on mouse fetus mitochondria. For this purpose different concentrations [1, 10 and 100%] of standardized cigarette smoke extract [CSE] were administrated on mitochondria isolated from fetus of NMRI mice on the 15 day of gestation. Our results showed a significant increase in ROS [Reactive oxygen species] formation, lipid peroxidation, mitochondrial membrane potential collapse, mitochondrial swelling and finally a decrease in ATP concentration in the CSE-treated isolated fetus mitochondria. Our results suggest that CSE-induced embryo toxicity is the result of disruptive effect on mitochondrial respiratory chain that leads to ROS formation, lipid peroxidation, mitochondrial MMP [mitochondrial membrane potential] decline and decrease of ATP level which starts apoptosis signaling

Toxicity of arsenic [III] on isolated liver mitochondria: a new mechanistic approach

Arsenic exposure mainly through food and water has been shown to be associated with increased incidence of numerous cancers and non-cancer harmful health. It is also used in cancer chemotherapy and treatment of several cancer types due to its apoptogenic effects in the various cancer and normal cell lines. We have already reported that liver is the storage site and important target organ in As [III] toxicity and recently, it has been suggested that hepatic toxicity of arsenic could be resulted from impairment of the liver mitochondria. In this study, interaction of As [III] with freshly isolated rat mitochondria was investigated. We determined different mitochondrial toxicity factors as well as mitochondrial sources of ROS formation using specific substrates and inhibitors following addition of As [III] to the mitochondria. Our results showed that arsenic [III] increased mitochondrial ROS formation, lipid peroxidation and mitochondrial membrane potential collapse, cytochrome c release and mitochondrial swelling in a concentration dependent manner. Addition of As [III] in to the isolated mitochondria, inhibited complexes I and II leading to disruption of mitochondrial electron transfer chain, decreased mitochondrial ATP content and ROS formation

Involvement of four different intracellular sites in chloroacetaldehyde- induced oxidative stress cytotoxicity

Chloroacetaldehyde [CAA] is a chlorination by-product in finished drinking water and a toxic metabolite of a wide variety of industrial chemicals [e.g. vinyl chloride] and chemotherapeutic agents [e.g. cyclophosphamide and ifosfamide]. In this research, the cytotoxic mechanisms of CAA in freshly isolated rat hepatocytes were investigated.CAA cytotoxicity was associated with reactive oxygen species [ROS] formation and glutathione depletion suggesting that oxidative stress contributed to the CAA cytotoxic mechanism. CAA-induced oxidative stress cytotoxicity markers were significantly prevented by antioxidants, ROS scavengers, mitochondrial permeability transition [MPT] pore sealing agents, endocytosis inhibitors, ATP generators and xanthine oxidase inhibitor. In our study the hepatocyte mitochondrial membrane potential was rapidly decreased by CAA which was prevented by antioxidants and ROS scavenger indicating that mitochondrial membrane damage was a consequence of ROS formation. CAA cytotoxicity was also associated with lysosomal membrane rupture. Our findings showed that at least four different intracellular sources including: metabolic enzymes cytochrome P[450] and xanthine oxidase, mitochondrial respiratory chain disruption and lysosomal Haber-weiss reaction, were involved in CAA induced ROS formation and other subsequent cytotoxic events. Our other interesting finding was that the lysosomotropic agents prevented CAA induced mitochondrial membrane potential collapse and mitochondrial MPT pore sealing agents inhibited lysosomal membrane damage caused by CAA. It can therefore be suggested that there is probably a toxic interaction [cross-talk] between mitochondrial and lysosomal oxidative stress generating systems, which potentiates each organelle damage and ROS formation in CAA- induced hepatotoxicity

Uranyl acetate induces oxidative stress and mitochondrial membrane potential collapse in the human dermal fibroblast primary cells

Cytotoxicity of depleted uranium, as a byproduct of military has been came to spotlight in recent decades. DU is known as a chemical rather than radioactive hazard and efforts to illustrating its mechanism is undergo, but the precise complete molecular mechanisms are still unclear. Recent studies showed that uranium induces biological changes in many different target tissues, such as the kidney, brain and skin. The aim of this study was to assess the impact of depleted uranium exposure at the cellular level in the human dermal fibroblast primary cells. The human dermal fibroblast primary cells incubated with different concentration [250-750 microM] of depleted uranium. Cytotoxicity and mitochondrial function in this cell lines were determined with the LDH leakage assay and the MTT test respectively. MDA levels were measured for determination of Lipid peroxidation in DU treated cells. Besides glutathione depletion and apoptosis phenotype detection were also assessed to complete the mechanistic screening. Results showed that the cell viability ameliorates in concentration and time dependent manners following in 24, 48 and 72 h incubation with DU. Moreover the significant increase in lipid peroxidation and significant decrease in cellular GSH recorded in DU treated human dermal fibroblast primary cells suggesting the preoxidant effect of uranyl ions. Cytoprotective effects of N-acetylcysteine [NAC] and dramatic decrease of cell viability in buthionin sulfoxamid [BSO] pretreated cells indicated the possibility of a critical role for glutathione system in DU detoxification. Death pattern, in fibroblast cells following DU treatment was varied from apoptosis to necrosis while the time and concentration increased. Since ROS formation is the initiation step for cell apoptosis, the present studies suggest Uranyl-induced toxicity in the human dermal fibroblast primary cells originated from oxidative stress and lead to occurrence of programmed cell death

effect of paroxetine on ouabain-induced toxicity in isolated guinea pig atria

It has been reported that selective serotonin reuptake inhibitors [SSRIs] possess some cardiac effects. In the present study we have investigated the effect of paroxetine [PX], a potent SSRI agent, on spontaneously as well as ouabain-induced arrhythmia beating isolated guinea-pig atria. The Guinea-pig heart was rapidly removed; the auricles were dissected out in oxygenated modified Krebs solution. The rate and force of spontaneous contractions were recorded isometrically with a photosensitive transducer. PX [1-16 micro g/ml] caused a dose-dependent decrease in the rate of contractions [14-70%] and contractile force [8-16%]. Ouabain alone [1.2 micro g/ml] produced arrhythmia at 7.2 +/- 1.5 min and asystole at 20.1 +/- 3.1 min. Pretreatment with PX [4 micro g/ml] significantly increased the time of arrhythmia onset to 19.8 min. In addition, PX prolonged the duration of action beating from 20.1 +/- 3.1 min to 43.1 +/- 2.6 and delayed the occurrence of asystole. The pattern of contractile force by PX + ouabain treatment was more regular than that observed after administration of ouabain alone. The above findings may the probably be due to the inhibition of cardiac Na[+] and Ca[2+] channels or autonomic nervous system. Results also suggest that PX may reduce the membrane conductance through inhibition of ionic channels to prevent ouabain-induced arrhythmia