A comparison of hepatocyte cytotoxic mechanisms for thallium (I) and thallium (III)

Pourahmad, Jalal; Eskandari, Mohammad Reza; Daraei, Bahram

doi:10.1002/tox.20590

Cited by 61 publications

(37 citation statements)

References 48 publications

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“…Cytotoxicity, ROS formation and mitochondrial membrane damage induced by lithium was interestingly potentiated by GSH and trifluoperazine. Also, depleting hepatocyte GSH beforehand prevented the hepatocytes against lithium induced cytotoxicity, ROS generation, mitochondrial membrane damage which reminds toxic reactions of GSH with some other metals including copper, chromium, uranium, cisplatin, and thallium O'Brien 2000, 2001;Pourahmad et al 2006Pourahmad et al , 2010aRiadh et al 2011). GSH is able to bind metal cations, a feature likely exploited by the cell during transport and delivery of metals (Ciriolo et al 1990).…”

Section: Discussionmentioning

confidence: 97%

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Glutathione mediated reductive activation and mitochondrial dysfunction play key roles in lithium induced oxidative stress and cytotoxicity in liver

et al. 2012

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Lithium preparations are commonly used drug in treating mental disorders and bipolar diseases, but metal's cytotoxic mechanisms have not yet been completely understood. In this study, we investigated the cytotoxic mechanisms of lithium in freshly isolated rat hepatocytes. Lithium cytotoxicity were associated with reactive oxygen species (ROS) formation and collapse of mitochondrial membrane potential and cytochrome c release into the hepatocyte cytosol. All of the mentioned lithium-induced cytotoxicity markers were significantly (P < 0.05) prevented by ROS scavengers, antioxidants, mitochondrial permeability transition pore sealing agents and adenosine triphosphate generators. Hepatocyte glutathione (GSH) was also rapidly oxidized and GSH-depleted hepatocytes were more resistant to lithium-induced oxidative stress markers. This suggests that lithium is activated by GSH. Our results also showed that CYP2E1 is involved in lithium oxidative stress mechanism. Lithium cytotoxicity was also associated with mitochondrial injuries initiated by increased ROS formation resulted from metal-CYP2E1 destructive interaction or metal-induced disruption of mitochondrial electron transfer chain. Methyl donors such as betaine, methionine, or folic acid prevented lithium cytotoxicity, and this suggests that this metal is detoxified by phase II metabolic methylation. In conclusion lithium-induced cytotoxicity could be attributed to oxidative stress and mitochondrial dysfunction.

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Section: Discussionmentioning

confidence: 97%

“…The viability of isolated hepatocytes was assessed from the intactness of the plasma membrane as determined by the trypan blue (0.2 % w/v) exclusion test (Pourahmad et al 2010a). Aliquots of the hepatocyte incubate were taken at different time points during the 3 h incubation period.…”

Section: Cell Viabilitymentioning

confidence: 99%

Glutathione mediated reductive activation and mitochondrial dysfunction play key roles in lithium induced oxidative stress and cytotoxicity in liver

et al. 2012

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“…As was establish in model systems and in animal cells the reactions of Tl(I) with reduced compounds produce Tl(0) and organic free radicals [71]. In plant cells these reactions might proceed by direct interactions with reduced components of the photosynthetic chain.…”

Section: Discussionmentioning

confidence: 99%

“…In plant cells these reactions might proceed by direct interactions with reduced components of the photosynthetic chain. Tl(0) and organic radicals subsequently react with the molecular oxygen producing superoxide (O 2 -• ), which is later dismutased to other reactive oxygen species (ROS) both by enzymatic and autocatalytic reactions [71]. ROS initiate the peroxidative chain reactions [40, 72, 73], among others they react with Tl(I) producing thallic ions Tl(III), a dangerous strong oxidant (E 0 Tl 3+ /Tl + = 1.2 V).…”

Section: Discussionmentioning

confidence: 99%

Overlapping toxic effect of long term thallium exposure on white mustard (Sinapis alba L.) photosynthetic activity

et al. 2016

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BackgroundHeavy metal exposure affect plant productivity by interfering, directly and indirectly, with photosynthetic reactions. The toxic effect of heavy metals on photosynthetic reactions has been reported in wide-ranging studies, however there is paucity of data in the literature concerning thallium (Tl) toxicity. Thallium is ubiquitous natural trace element and is considered the most toxic of heavy metals; however, some plant species, such as white mustard (Sinapis alba L.) are able to accumulate thallium at very high concentrations. In this study we identified the main sites of the photosynthetic process inhibited either directly or indirectly by thallium, and elucidated possible detoxification mechanisms in S. alba.ResultsWe studied the toxicity of thallium in white mustard (S. alba) growing plants and demonstrated that tolerance of plants to thallium (the root test) decreased with the increasing Tl(I) ions concentration in culture media. The root growth of plants exposed to Tl at 100 μg L−1 for 4 weeks was similar to that in control plants, while in plants grown with Tl at 1,000 μg L−1 root growth was strongly inhibited. In leaves, toxic effect became gradually visible in response to increasing concentration of Tl (100 − 1,000 μg L−1) with discoloration spreading around main vascular bundles of the leaf blade; whereas leaf margins remained green. Subsequent structural analyses using chlorophyll fluorescence, microscopy, and pigment and protein analysis have revealed different effects of varying Tl concentrations on leaf tissue. At lower concentration partial rearrangement of the photosynthetic complexes was observed without significant changes in the chloroplast structure and the pigment and protein levels. At higher concentrations, the decrease of PSI and PSII quantum yields and massive oxidation of pigments was observed in discolored leaf areas, which contained high amount of Tl. Substantial decline of the photosystem core proteins and disorder of the photosynthetic complexes were responsible for disappearance of the chloroplast grana.ConclusionsBased on the presented results we postulate two phases of thallium toxicity on photosynthesis: the non-destructive phase at early stages of toxicant accumulation and the destructive phase that is restricted to the discolored leaf areas containing high toxicant content. There was no distinct border between the two phases of thallium toxicity in leaves and the degree of toxicity was proportional to the migration rate of the toxicant outside the vascular bundles. The three-fold (nearly linear) increase of Tl(I) concentration was observed in damaged tissue and the damage appears to be associated with the presence of the oxidized form of thallium − Tl(III).Electronic supplementary materialThe online version of this article (doi:10.1186/s12870-016-0883-4) contains supplementary material, which is available to authorized users.

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“…On the other hand V 5+ also promoted ROS formation and cell death, when incubated with GSH. Also, depleting heaptocyte GSH beforehand prevented the hepatocytes against V 5+ -induced cytotoxicity, ROS generation, mitochondrial membrane damage which reminds toxic reactions of GSH with some other metals including copper, chromium, uranium, thallium and lithium [18,[32][33][34][35][36]. Thiol compounds especially when dissociated to their thiolate anion (R-S-) forms can in fact affect the reduction of metal cations, for example, iron and copper.…”

Section: Discusionmentioning

confidence: 99%

Vanadium induces liver toxicity through reductive activation by glutathione and mitochondrial dysfunction

Hosseini¹,

Seyedrazi²,

Shahraki³

et al. 2012

ABB

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Pentavalent vanadium (V 5+) (metavanadate salt) toxicity is a challenging problem to the health professionals and has been recognized as an industrial hazard that adversely affects human and animal health, but its cytotoxic mechanisms have not yet been completely understood. In this study, we investigated the cytotoxic mechanisms of V 5+ in freshly isolated rat hepatocytes. V 5+ cytotoxicity was associated with reactive oxygen species (ROS) formation, collapse of mitochondrial membrane potential, lysosomal membrane rupture and cytochrome c release into the hepatocyte cytosol. All of the above mentioned V 5+ -induced cytotoxicity markers were significantly (p < 0.05) prevented by ROS scavengers, antioxidants and mitochondrial permeability transition (MPT) pore sealing agents. Hepatocyte glutathione (GSH) was also rapidly oxidized and GSH-depleted hepatocytes were more resistant to lithium-induced oxidative stress markers. This suggests that V 5+ is activated by GSH. Our findings also showed that the lysosomotropic agents prevented V 5+ induced mitochondrial membrane potential collapse. On the other hand, mitochondrial MPT pore sealing agents inhibited lysosomal membrane damage caused by V 5+ . It can therefore be suggested that there is probably a toxic interaction (cross-talk) between mitochondrial and lysosomal oxidative stress generating systems, which potentiates ROS formation and further damages both sub-organelles in V 5+ -induced induced hepatotoxicity. In conclusion, V 5+ -induced cytotoxicity can be attributed to oxidative stress started from glutathione mediated metal reductive activation and continued by mitochondrial/lysosomal toxic interaction.

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A comparison of hepatocyte cytotoxic mechanisms for thallium (I) and thallium (III)

Cited by 61 publications

References 48 publications

Glutathione mediated reductive activation and mitochondrial dysfunction play key roles in lithium induced oxidative stress and cytotoxicity in liver

Glutathione mediated reductive activation and mitochondrial dysfunction play key roles in lithium induced oxidative stress and cytotoxicity in liver

Overlapping toxic effect of long term thallium exposure on white mustard (Sinapis alba L.) photosynthetic activity

Vanadium induces liver toxicity through reductive activation by glutathione and mitochondrial dysfunction

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