Zinc and selenium supplement mitigated valproic acid-induced testis toxicity by modulating the oxidative redox balance in male rats / 대한해부학회지

Valproic acid (VPA) is widely used antiepileptic agent which is associated with reproductive toxicity via impairment in oxidative redox. Zinc (Zn) and selenium (Se) are trace element with antioxidant effect that known to be essential for spermatogenesis. In the current study, the protective effect of co-administration of Zn and Se on VPA-induced reproductive toxicity in male rats was evaluated. Forty-eight male rats were divided into 8 groups of six (n=6): Control group (treated with normal saline); VPA only (250, 500, 1,000 mg/kg) group; VPA (500 mg/kg) plus Zn (2 mg/kg) group; VPA (500 mg/kg) plus Se (1.5 mg/kg) group; VPA (500 mg/kg) plus a combination of Zn and Se group; and VPA+vitamin E (20 mg/kg) group. The Animals were sacrificed after 28 days of treatment and sperm analysis was taken. Also, evaluation of oxidative stress markers including malondialdehyde (MDA), protein carbonyl (PC), glutathione (GSH) and histopathological changes were done on testis tissue. Morphological changes and a significant decrease in motility and sperm count in rats treated with VPA were observed. Also, an increase in oxidative stress marker, including MDA and PC and a decrease in GSH level was evident in VPA group. Zn and Se administration was able to protect against sperm abnormality, ameliorate the histological change in testis tissue, and suppressed the increase in oxidative stress markers induced by VPA. These results indicated that combination therapy with Zn and Se showed better an ameliorative effect than each one alone. Therefore, it can be suggested as an effective supplement for reproductive impairment in VPA-treated patient.

Zinc and selenium supplement mitigated valproic acid-induced testis toxicity by modulating the oxidative redox balance in male rats / 대한해부학회지

Valproic acid (VPA) is widely used antiepileptic agent which is associated with reproductive toxicity via impairment in oxidative redox. Zinc (Zn) and selenium (Se) are trace element with antioxidant effect that known to be essential for spermatogenesis. In the current study, the protective effect of co-administration of Zn and Se on VPA-induced reproductive toxicity in male rats was evaluated. Forty-eight male rats were divided into 8 groups of six (n=6): Control group (treated with normal saline); VPA only (250, 500, 1,000 mg/kg) group; VPA (500 mg/kg) plus Zn (2 mg/kg) group; VPA (500 mg/kg) plus Se (1.5 mg/kg) group; VPA (500 mg/kg) plus a combination of Zn and Se group; and VPA+vitamin E (20 mg/kg) group. The Animals were sacrificed after 28 days of treatment and sperm analysis was taken. Also, evaluation of oxidative stress markers including malondialdehyde (MDA), protein carbonyl (PC), glutathione (GSH) and histopathological changes were done on testis tissue. Morphological changes and a significant decrease in motility and sperm count in rats treated with VPA were observed. Also, an increase in oxidative stress marker, including MDA and PC and a decrease in GSH level was evident in VPA group. Zn and Se administration was able to protect against sperm abnormality, ameliorate the histological change in testis tissue, and suppressed the increase in oxidative stress markers induced by VPA. These results indicated that combination therapy with Zn and Se showed better an ameliorative effect than each one alone. Therefore, it can be suggested as an effective supplement for reproductive impairment in VPA-treated patient.

Nanoceria attenuated high glucose-induced oxidative damage in hepg2 cells

Objective: Hyperglycemia, a common metabolic disorder in diabetes, can lead to oxidative damage. The use of antioxidants can benefit the control and prevention of diabetes side effects. This study aims to evaluate the effect of nanoceria particles, as an antioxidant, on glucose induced cytotoxicity, reactive oxygen species [ROS], lipid peroxidation [LPO] and glutathione [GSH] content in a human hepatocellular liver carcinoma cell line [HepG2] cell line

Materials and Methods: In this experimental study, we divided HepG2 cells into these groups: i. Cells treated with 5 mM D-glucose [control], ii. Cells treated with 45 mM Dmannitol+ 5 mM D-glucose [osmotic control], iii. Cells treated with 50 mM D-glucose [high glucose], and iv. Cells treated with 50 mM D-glucose+nanoceria. Cell viability, ROS formation, LPO and GSH were measured and analyzed statistically

Results: High glucose [50 mM] treatment caused significant cell death and increased oxidative stress markers in HepG2 cells. Interestingly, nanoceria at a concentration of 50 mM significantly decreased the high glucose-induced cytotoxicity, ROS formation and LPO. This concentration of nanoceria increased the GSH content in HepG2 cells [P<0.05]

Conclusion: The antioxidant feature of nanoceria particles makes it an attractive candidate for attenuation of hyperglycemia oxidative damage in different organs

Embryo toxic effects of depleted uranium on the morphology of the mouse fetus

Although the biokinetics, metabolism, and chemical toxicity of uranium are well known, until recently little attention was paid to the potential toxic effects of uranium on reproduction and development in mammals. In recent years, it has been shown that uranium is a developmental toxicant when given orally or subcutaneously [SC] to mice. Decreased fertility, embryo/fetal toxicity including teratogenicity, and reduced growth of the offspring have been observed following uranium exposure at different gestation periods. For investigating the effects of DU on pregnant animals, three groups [control, sham and test] of NMRI mice were chosen. In test group 4mg/kg of DU were administered intraperitonealy at 11 day of gestation, in sham group only normal saline injected to interior peritoneum as indicated in the test group and in Control group which was considered as the comparison base line of our research, no injection was made. Caesarean sections were performed at 15 day of the gestation; and their placentas were examined externally. Base on our results DU caused significant external anomalies, and caused a significant decrease [p<0.05] in the weight and diameter of placentas, the number of the embryos, their body weight and crown-rump length of fetuses

Occurrence of deoxynivalenol in foods for human consumption from Tehran, Iran

The occurrence of deoxynivalenol [DON] in retail foods in Tehran [Iran] was determined using high-performance liquid chromatography technique and immunoaffinity column as the clean-up step. A method was validated for analysis of DON in rice, bread, puffed corn snack and wheat flour. The average recoveries and precision [RSD] for DON in different foods ranged 84.2-93.1% and 2.9-12.0%, respectively. A survey of DON was performed on the 72 samples of rice, bread, puffed corn snack, and wheat flour collected from Tehran retail market. The data showed that 10 samples [13.9%] out of 72 samples were contaminated with DON with the maximum level of 368.7 ng/g. The samples had contamination level lower than the maximum tolerated level of DON in foods in Iran. The total intake of DON was under the provisional maximum tolerable daily intake set for DON by the JECFA

Edaravone decreases paraquat toxicity in a549 cells and lung isolated mitochondria

Edaravone, an antioxidant and radical scavenger, showed protective effects against oxidative stress-like condition. Paraquat [PQ] is toxic herbicide considerable evidence suggests that oxidative stress and mitochondrial dysfunction contribute to PQ toxicity. In this study, protective effect of edaravone against PQ induced toxicity and reactive oxygen species [ROS] generation in A549 cells and lung isolated mitochondria were evaluated. A549 cells and lung isolated mitochondria were divided into control group, PQ group, edaravone group and PQ plus edaravone-pretreated group. Cellular and mitochondrial viability assayed using MTT test and ROS generations in both cellular and mitochondrial fraction were determined by fluorometry using DCFH-DA as indicator. Our results showed that edaravone [5-100 microM] prevented PQ [500 microM] induced cytotoxicity in A549 celIs that the best protective effect was observed at concentration of 50 microM of edaravone. In addition, PQ-induced ROS generation in A549 cells significantly inhibited by edaravone. Moreover, PQ decreased mitochondria viability and also increased ROS generation in lung isolated mitochondria that edaravone [25-400 microM] markedly inhibited these toxic effects. In overall, the results of this study suggest that lung mitochondria maintenance is essential for maintaining PQt cytotoxicity and Edaravone is a protective drug against PQ toxicity in-vitro

Mitochondrial toxicity of depleted uranium: protection by beta-glucan

Considerable evidence suggests that mitochondrial dysfunction contributes to the toxicity of uranyl acetate [UA], a soluble salt of depleted uranium [DU]. We examined the ability of the two antioxidants, beta-glucan and butylated hydroxyl toluene [BHT], to prevent UA-induced mitochondrial dysfunction using rat-isolated kidney mitochondria. Beta-glucan [150 nM] and BHT [20 nM] attenuated UA-induced mitochondrial reactive oxygen species [ROS] formation, lipid peroxidation and glutathione oxidation. Beta-glucan and BHT also prevented the loss of mitochondrial membrane potential [MMP] and mitochondrial swelling following the UA treatment in isolated mitochondria. Our results show that beta-glucan and BHT prevented UA-induced mitochondrial outer membrane damage as well as release of cytochrome c from mitochondria. UA also decreased the ATP production in isolated mitochondria significantly inhibited with beta-glucan and BHT pre-treatment. Our results showed that beta-glucan may be mitochondria-targeted antioxidant and suggested this compound as a possible drug candidate for prophylaxis and treatment against DU-induced nephrotoxicity

Analysis of aflatoxin B1 in Iranian foods using HPLC and a monolithic column and estimation of its dietary intake

A high performance liquid chromatographic method was developed for determination of aflatoxin B1 [AFB1] in foods using a monolithic column with sample clean up on an immunoaffinity column. The method was validated for analysis of AFB1 in rice, bread, puffed corn snack, wheat flour and peanut samples. The average recoveries for AFB1 in different foods ranged from 94.4 to 102.5% with the coefficient of variation lower than 10% for all foods. Limit of detection was 0.01 ng/g. A survey of AFB1 was performed on 90 samples collected from Tehran retail market in June 2005. The results showed that none of the bread and wheat flour samples were contaminated with AFB1. The mean AFB1 levels in rice, puffed corn snack and peanut samples were 4.17, 0.11, and 1.97 ng/g, respectively. The level of contamination of 3 samples [one rice sample and two peanuts samples] to AFB1 was found to be higher than 5 ng/g. Although all food samples had mean concentration of AFB1 below the maximum tolerated level in Iran, the mean intake of AFB1 from rice was estimated 3.49 times higher than the guidance value of 1 ng AFB1/Kg body weight/day. Therefore, it is strongly recommended to monitor AFB1 in foods, especially in rice, in Iran. This is the first study on exposure assessment of Iranian population to AFB1

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

Mercury exposure of gold mining workers in the northwest of Iran

Mercury exposure is a health concern in the occupational settings like gold mining and chloralkali industries and blood and urine levels of mercury are used as exposure indicators. In this study, blood and urine concentrations of mercury were determined using hydride generation atomic absorption spectrophotometery [HGAAS] in sixteen gold miners with neuropsychiatric symptoms. The patients treated with two chelating agents, dimercaprol and D-penicillamine. The mean serum mercury levels before and after chelation therapy were 208.14 Micro g/L[-1] and 10.50 Micro g/L[-1], respectively. The mean urinary mercury levels before and after chelation therapy were 134.70 Micro g/L[-1] and 17.23 Micro g/L[-1], respectively. The results of this study showed that there are significant differences between concentration of blood and urine mercury before and after intervention [p<0.005]. There were no significant differences between in the biochemistry parameters of patients before and after treatment. This study indicated that the gold miners in the northwest of Iran had been exposed to high levels of mercury vapors [Hg[0]]

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