Ebselen (Ebs) and diphenyl diselenide [(PhSe)(2)] readily oxidize thiol groups. Here we studied mitochondrial swelling changes in mitochondrial potential (Deltapsim), NAD(P)H oxidation, reactive oxygen species production, protein aggregate formation, and oxygen consumption as ending points of their in vitro toxicity. Specifically, we tested the hypothesis that organochalchogens toxicity could b...

The objective of the present study was to assess the capacity of nonsynaptic brain mitochondria to accumulate Ca2+ when subjected to repeated Ca2+ loads, and to explore under what conditions a mitochondrial permeability transition (MPT) pore is assembled. The effects of cyclosporin A (CsA) on Ca2+ accumulation and MPT pore assembly were compared with those obtained with ubiquinone 0 (Ubo), a qu...

Etoposide (VP-16) is known to promote cell apoptosis either in cancer or in normal cells as a side effect. This fact is preceded by the induction of several mitochondrial events, including increase in Bax/Bcl-2 ratio followed by cytochrome c release and consequent activation of caspase-9 and -3, reduction of ATP levels, depolarization of membrane potential (DeltaPsi) and rupture of the outer me...

Whereas alpidem is hepatotoxic, zolpidem is not. Despite closely related chemical structures, alpidem, but not zolpidem, is a peripheral benzodiazepine receptor (PBR) ligand, and is also more lipophilic than zolpidem. We compared their effects in isolated rat liver mitochondria and rat hepatocytes. Zolpidem did not affect calcium-induced mitochondrial permeability transition (MPT) in mitochondr...

ATP decreases markedly in small-for-size liver grafts. This study tested if the mitochondrial permeability transition (MPT) underlies dysfunction of small-for-size livers. Half-size livers were implanted into recipients of about twice the donor weight, resulting in quarter-size liver grafts. NIM811 (5 microM), a nonimmunosuppressive MPT inhibitor was added to the storage solutions. Mitochondria...

Much of cell death from ischaemia/reperfusion in heart and other tissues is generally thought to arise from mitochondrial permeability transition (MPT) in the first minutes of reperfusion. In ischaemic pre-conditioning, agonist binding to G(i) protein-coupled receptors prior to ischaemia triggers a signalling cascade that protects the heart from MPT. We believe that the cytosolic component of t...

Ethanol increases the vulnerability of mitochondria to induction of the mitochondrial permeability transition (MPT). Cyclophilin-D activity enhances the potential for the permeability transition pore (PTP) to open. In the present study, we demonstrate that ethanol and its metabolism sensitize the PTP to opening, in part by increasing the acetylation and activity of cyclophilin-D. This effect of...

To simulate ischemia and reperfusion, cultured rat hepatocytes were incubated in anoxic buffer at pH 6.2 for 4 h and reoxygenated at pH 7.4. During anoxia, intracellular pH (pHi) decreased to 6.3, mitochondria depolarized, and ATP decreased to <1% of basal values, but the mitochondrial permeability transition (MPT) did not occur as assessed by confocal microscopy from the redistribution of cyto...

6- Mercaptopurine (6-MP) is widely used in clinic as an immunosuppressive for treatment of acute lymphocytic leukemia, Crohn's disease, and ulcerative colitis with documented unpredictable hepatotoxicity. The potential molecular cytotoxic mechanisms of 6-MP against isolated rat hepatocytes were searched in this study using “Accelerated Cytotoxicity Mechanism Screening (ACMS)” techniques. The co...

Modulation of K(+) conductance of the inner mitochondrial membrane has been proposed to mediate preconditioning in ischemia-reperfusion injury. The mechanism is not entirely understood, but it has been linked to a decreased activation of mitochondrial permeability transition (mPT). In the present study K(+) channel activity was mimicked by picomolar concentrations of valinomycin. Isolated brain...