Butylated hydroxytoluene prevents cumene hydroperoxide-induced Ca2+ release from liver mitochondria by inhibiting pyridine nucleotide hydrolysis

Gogvadze, Vladimir; Kass, George E.N.; Boyer, C S; Zhukova, Aleksandra; Kim, Y.; Orrenius, Sten

doi:10.1016/0006-291x(92)91682-g

Cited by 11 publications

(6 citation statements)

References 21 publications

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“…In contrast, BHA did not interact directly with BVDV, since preincubation of the virus with BHA for 1 h at 37 mC did not reduce virus infectivity (not shown). Additionally, BHT (Gogvadze et al, 1992) and cyclosporine A (CSA) (Schweizer et al, 1993) inhibit ROS-induced Ca# + -cycling in mitochondria, an important factor in ROS-induced apoptosis (Richter, 1993). However, BHT was much more toxic to BT cells than was BHA, which is also observed in hepatocytes (Thompson & Molde!…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress in cells infected with bovine viral diarrhoea virus: a crucial step in the induction of apoptosis.

Schweizer

Peterhans

1999

Journal of General Virology

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Bovine viral diarrhoea virus (BVDV) belongs to the genus Pestivirus of the family Flaviviridae. Both a noncytopathic (ncp) and an antigenically related cytopathic (cp) BVDV can be isolated from persistently infected animals suffering from mucosal disease. In every case studied so far, the genomic changes leading to the cp biotype correlate with the production of the NS3 nonstructural protein, which, in the ncp biotype, is present in its uncleaved form, NS23. This report shows that, in contrast to ncp BVDV, the cp biotype induces apoptosis in cultured embryonic bovine turbinate cells. Early in the process of apoptosis, cells show a rise in the intracellular level of reactive oxygen species, which is indicative of oxidative stress. This precedes two hallmarks of apoptosis, caspase activation as shown by cleavage of the caspase substrate poly(ADP-ribose) polymerase, and DNA fragmentation. Cells were protected from apoptosis only by certain antioxidants (butylated hydroxyanisole and ebselen), whereas others (N-acetylcysteine, pyrrolidine dithiocarbamate, lipoic acid, dihydrolipoic acid and tiron) turned out to be ineffective. Antioxidants that protected cells from apoptosis prevented oxidative stress but failed to block virus growth. These observations suggest that oxidative stress, which occurs early in the interaction between cp BVDV and its host cell, may be a crucial event in the sequence leading to apoptotic cell death. Hence, apoptosis is not required for the multiplication of the cp biotype of BVDV.

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Section: Discussionmentioning

confidence: 99%

Oxidative stress in cells infected with bovine viral diarrhoea virus: a crucial step in the induction of apoptosis.

Schweizer

Peterhans

1999

Journal of General Virology

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“…Intracellular calcium elevation has been linked to iron-induced free radical generation and lipid peroxidation (Josephson et al, 1991;Rojanasakul et al, 1993). Free radical formation has been shown to increase calcium influx through voltage-gated calcium channels (Josephson et al, 1991) and free radical scavengers have prevented peroxide-mediated calcium release (Gogvadze et al, 1992). In addition, free radical production may lead to neurotransmitter mediated excitotocity, as free radicals in the medium surrounding a brain slice cause excess glutamate and aspartate release (Pellegrini-Giampietro et al, 1990).…”

Section: Iron and Free Radical Formationmentioning

confidence: 99%

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

1994

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Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.

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“…However, the latter may only apply to the extent that boldine interferes with nonlipoperoxidative events which account mechanistically for the cytotoxic effects of the lower TBOOH concentration. Many oxidants, including TBOOH, have shown to be able to induce damage to hepatocytes via Ca2÷-dependent mechanisms (Kass et al, 1992). According to Orrenius (1993), a cytotoxic perturbation of cellular Ca 2÷ homeostasis can be induced by several oxidants through a mechanism involving the oxidation of cellular thiols and pyridine nucleotides, followed by the inhibition of Ca2+-translocases.…”

Section: Discussionmentioning

confidence: 99%

“…Pyridine nucleotide oxidation is necessary -although not sufficient -to cause mitochondrial Ca 2+ release, and requires subsequent hydrolysis. Cyclosporin A protects hepatocytes from cell death induced by TBOOH, and the mechanism of such protection has been shown to involve the inhibition of Ca 2÷ release from mitochondria and its subsequent transport across the inner mitochondrial membrane (Kass et al, 1992;Rubin and Farber, 1984). Recently, butylated hydroxytoluene (BHT), a potent antioxidant which protects hepatocytes against cumene hydroperoxide-induced damage, was also shown to inhibit pyridine nucleotide hydrolysis and to prevent the subsequent release of Ca 2÷ from liver mitochondria (Gogvadze et al, 1992;Orrenius, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…Cyclosporin A protects hepatocytes from cell death induced by TBOOH, and the mechanism of such protection has been shown to involve the inhibition of Ca 2÷ release from mitochondria and its subsequent transport across the inner mitochondrial membrane (Kass et al, 1992;Rubin and Farber, 1984). Recently, butylated hydroxytoluene (BHT), a potent antioxidant which protects hepatocytes against cumene hydroperoxide-induced damage, was also shown to inhibit pyridine nucleotide hydrolysis and to prevent the subsequent release of Ca 2÷ from liver mitochondria (Gogvadze et al, 1992;Orrenius, 1993). It remains to be established whether boldine, like BHT, is also able to interfere with the mitochondrial-related events which lead to a perturbation in Ca 2+ homeostasis, even though it has been suggested that this alkaloid blocks Ca 2+ entry without affecting intracellular stores (Ivorra et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

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Cytoprotective and antioxidant effects of boldine on tert-butyl hydroperoxide?induced damage to isolated hepatocytes

Bannach¹,

Valenzuela²,

Cassels

et al. 1996

Cell Biol Toxicol

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Boldine, an aporphine alkaloid, was recently shown by us to exhibit potent antioxidant properties. We report here that boldine concentration-dependently inhibited the peroxidative (accumulation of thiobarbituric acid reactive substances) and lytic damage (trypan blue exclusion and lactate dehydrogenase leakage) to isolated rat hepatocytes induced by tert-butyl hydroperoxide (TBOOH). Boldine (200 micromol/L) fully cytoprotected and completely prevented the peroxidation induced by TBOOH at concentrations equal to or lower than 0.87 mmol/L. However, at a peroxide concentration of 0.91 mmol/L, although boldine completely inhibited lipid peroxidation it largely failed to afford cytoprotection against TBOOH. TBOOH alone (0.83 mmol/L) caused an early (within 60 s) sudden decline of reduced glutathione (by 50%) and an equivalent increase in the levels of oxidized glutathione. Neither of these effects was prevented by the simultaneous addition of a cytoprotective and antioxidant concentration of boldine (200 micromol/L). The delayed addition of boldine to the suspension (after 10 or 20 min), while effectively blocking any further increase in thiobarbituric acid reactive substances, totally failed to prevent the peroxide-induced loss in cell viability. Conversely, preincubation of the hepatocytes with boldine for 150 min (at which time no boldine could be detected in either intra- or extracellular spaces) prevented lipid peroxidation and was as effective in protecting the cells against the damage caused by the subsequent addition of TBOOH as the simultaneous addition of boldine and TBOOH to hepatocytes preincubated for 150 min under control conditions.

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Butylated hydroxytoluene prevents cumene hydroperoxide-induced Ca2+ release from liver mitochondria by inhibiting pyridine nucleotide hydrolysis

Cited by 11 publications

References 21 publications

Oxidative stress in cells infected with bovine viral diarrhoea virus: a crucial step in the induction of apoptosis.

Oxidative stress in cells infected with bovine viral diarrhoea virus: a crucial step in the induction of apoptosis.

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Cytoprotective and antioxidant effects of boldine on tert-butyl hydroperoxide?induced damage to isolated hepatocytes

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