Induction of oxidative stress by selenomethionine in isolated hepatocytes of rainbow trout (Oncorhynchus mykiss)

Department of Biology, University of Saskatchewan, 112 Science Place, Saskatoon, SK, Canada S7N 5E2.
Toxicology in Vitro (Impact Factor: 2.9). 02/2012; 26(4):621-9. DOI: 10.1016/j.tiv.2012.02.001
Source: PubMed


Fish are exposed to environmental selenium predominantly in the form of dietary selenomethionine (SeMet). The present study was designed to investigate the role of oxidative stress in the toxicity of SeMet using isolated hepatocytes of rainbow trout (Oncorhynchus mykiss) as the model experimental system. Cells were exposed to an increasing range of SeMet (0-1000 μM) over 24h, and the time-dependent effects on cell viability, response of enzymatic antioxidants, thiol redox, intracellular calcium balance and caspase-mediated apoptosis were evaluated. SeMet was found to be toxic only at the highest exposure dose (1000 μM), with ∼15% decrease in cell viability. Although modest increases in the activities of antioxidant enzymes were recorded following SeMet exposure, the ratio of reduced to oxidized glutathione decreased in a dose-dependent manner, suggesting a gradual progression towards an oxidative intracellular environment. The peroxidation of membrane lipids also increased with increasing SeMet exposure dose. In addition, a rapid increase in intracellular calcium level and the activation of caspase 3/7 enzymes were recorded at the highest exposure dose, indicating that SeMet at a high exposure dose causes cell death probably via apoptosis. Overall, our study demonstrated that oxidative stress plays a key role in the cytotoxicity of SeMet in fish.

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    • "The most important antioxidant enzymes linked with antioxidant defenses against oxidative stress are glutathione peroxidase, reductase, and transferase (Hayes and McLellan 1999). The activity of antioxidant enzymes, such as GPx and other markers of oxidative stress, has been extensively used in fish both in vivo and in vitro studies (Dörr et al. 2008; Misra and Niyogi 2009; Misra et al. 2012). "
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    ABSTRACT: The present study was conducted to evaluate the effects of vaccination against furunculosis on responses of oxidative stress and antioxidant defenses in rainbow trout Oncorhynchus mykiss muscle, gills, liver, and brain tissues. The oxidative stress markers (malondialdehyde and carbonyl derivatives of protein oxidative destruction levels), antioxidant defenses (superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase), and total antioxidant capacity in different tissues of rainbow trout were measured. Our data showed that exposure of trout to vaccine against furunculosis produced changes (either increase or decrease) in oxidative stress and antioxidant enzymes responses, and these responses showed marked organ differences, associated with tissue patterns. Our study demonstrated that vaccinated trout showed alteration in antioxidant defenses and oxidative stress responses, with higher severity in the liver, compared with other tissues. Our data also suggest that vaccination against furunculosis induced lipid peroxidation in gill and liver tissues. However, muscle and brain tissue are capable of restoring its pro- and antioxidant balance after vaccination.
    Full-text · Article · Mar 2014 · Fish Physiology and Biochemistry
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    • "Lately, Cys- Se-Se-Cys has received more attention due to its potential use as a food/feed additive and its pharmacological applications. Moreover , recent studies have shown that Cys-Se-Se-Cys is the principal metabolite in the liver of fish feed organic selenium compounds, as SeMet (Misra et al., 2012a). However, to date only few investigations have been conducted on the balance between the beneficial and toxic effects of this diselenocompound (El-Sayed et al., 2006; Santhosh Kumar et al., 2009). "
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    ABSTRACT: Selenium (Se) is an oligonutrient with both essential biological functions and recognized harmful effects. As the selenocysteine (SeCys) amino acid, selenium is integrated in several Se-containing proteins (selenoproteins), many of which are fundamental for cell homeostasis. Nevertheless, selenium may exert toxic effects at levels marginally above those required, mainly through the generation of reactive oxygen species (ROS). The selenium chemical speciation can strongly affect the bioavailability of this metal and its impact on metabolism, dictating the levels that can be beneficial or detrimental towards an organism.
    Full-text · Article · Jan 2013 · Aquatic toxicology (Amsterdam, Netherlands)
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    • "The cellular lipid peroxidation tends to enhance with increasing selenite exposure dose leading to increase of cell death associated with caspase-3/7 activity [56]. A similar behavior was observed with SeMet in the same biological model [57]. On the other hand, Chen et al. [58] in a study with three compounds i.e., sodium selenite, selenocystamine and diselenodipropionic acid (DSePA) (Figure 7), observed provoked oxidation of glutathione with superoxide generation suggesting that the catalytic species producing superoxide were the GSSe− or RSe− anion. "
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    ABSTRACT: Selenium (Se) is an essential trace element involved in different physiological functions of the human body and plays a role in cancer prevention and treatment. Induction of apoptosis is considered an important cellular event that can account for the cancer preventive effects of Se. The mechanisms of Se-induced apoptosis are associated with the chemical forms of Se and their metabolism as well as the type of cancer studied. So, some selenocompounds, such as SeO(2) involve the activation of caspase-3 while sodium selenite induces apoptosis in the absence of the activation of caspases. Modulation of mitochondrial functions has been reported to play a key role in the regulation of apoptosis and also to be one of the targets of Se compounds. Other mechanisms for apoptosis induction are the modulation of glutathione and reactive oxygen species levels, which may function as intracellular messengers to regulate signaling pathways, or the regulation of kinase, among others. Emerging evidence indicates the overlaps between the apoptosis and other types of cell death such as autophagy. In this review we report different processes of cell death induced by Se compounds in cancer treatment and prevention.
    Full-text · Article · Dec 2012 · International Journal of Molecular Sciences
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