Cytotoxic mechanisms of hydrosulfide anion and cyanide anion in primary rat hepatocyte cultures

Mitochondrial depolarization following hydrogen sulfide exposure in erythrocytes from a sulfide-tolerant marine invertebrate

“…Taken together, the irreversibility of sulfide and the absence of a similar effect from other COX inhibitors provide strong evidence that the mechanism by which sulfide causes mitochondrial depolarization is not via COX inhibition. A similar conclusion was reached by Thompson et al (2003) who, like Eghbal et al (2004), studied the effect of sulfide on primary rat hepatocytes in culture. Thompson et al (2003) found that hepatocytes exposed to sulfide or cyanide were killed in a dose-dependent manner, as expected, but differed in their response to supplementation by glycolytic substrate.…”

“…A similar conclusion was reached by Thompson et al (2003) who, like Eghbal et al (2004), studied the effect of sulfide on primary rat hepatocytes in culture. Thompson et al (2003) found that hepatocytes exposed to sulfide or cyanide were killed in a dose-dependent manner, as expected, but differed in their response to supplementation by glycolytic substrate. Specifically, addition of fructose to the hepatocytes, which greatly enhances glycolytic ATP production in these cells (Nieminen et al, 1994), substantially decreased the toxicity of cyanide, but had no effect on the toxicity of sulfide, and the PT pore inhibitors CsA and TFP decreased cell death during sulfide exposure but not during cyanide exposure (Thompson et al, 2003).…”

“…With regard to sulfide exposure, one study has reported that isolated rat hepatocytes exposed to 0.5·mmol·l -1 sulfide in vitro lost over 50% of ⌬⌿m within 1·h, and that this effect was reduced when the cells were supplemented with glycolytic substrate (Eghbal et al, 2004). In contrast, another study on the same cell type reported that supplementation with glycolytic substrate had no effect on cell survival during sulfide exposure, although it did increase cell survival during cyanide exposure (Thompson et al, 2003). Therefore, whether sulfide exposure causes cellular toxicity via decreased ⌬⌿m is unclear.…”

“…To determine whether the change in ⌬⌿m from sulfide exposure is dependent on opening of the mitochondrial PT pore, G. dibranchiata erythrocytes were exposed to sulfide for 1·h, as described above, except that the PT pore inhibitor pair cyclosporine A (CsA; 0.5·mol·l -1 ) and trifluoperazine (TFP; 5·mol·l -1 ) were added to the erythrocytes 30·min prior to initiation of sulfide exposure (Thompson et al, 2003). Control erythrocytes at each sulfide concentration were exposed to sulfide alone or sulfide with CCCP (0.10·mmol·l -1 ).…”

“…In either case, MOMP leads inexorably to cell death through the release of pro-apoptotic factors from the mitochondrial inter-membrane space into the cytosol (He and Lemasters, 2002;Hunter et al, 1976;Kim et al, 2003a;Ly et al, 2003). In rat hepatocytes in vitro, the PT pore inhibitors cyclosporine A (CsA) and trifluoperazine (TFP) decreased sulfide-induced cell death by 50% compared to sulfide alone, but had no effect on cyanide-induced cell death (Thompson et al, 2003), suggesting that sulfide and cyanide cause cell death via different mechanisms. Therefore, in contrast to cyanide, which in mammalian cells does not necessarily dissipate ⌬⌿m (Lawrence et al, 2001) and may not induce PT pore opening (Thompson et al, 2003), sulfide exposure of mammalian cells in vitro causes loss of ⌬⌿m that appears to be at least partially via PT pore opening (Eghbal et al, 2004;Thompson et al, 2003).…”