The respiration-impairing effect of rubroskyrin, a toxic metabolite

Abstract

The toxic effect of rubroskyrin, a modified bis-anthraquinone pigment fromPenicillium islandicum Sopp, on mitochondrial respiration has been studied by using isolated rat liver mitochondria, comparing with those of luteoskyrin and rugulosin which are well knownislandicum toxins. It was found that rubroskyrin exerted an uncoupling effect on mitochondrial respiration, abating the respiratory control ratio (RCR) by a dose dependent manner (UD50: 10 μM) and markedly depressed state 3 respiration at high concentrations, whereas such respiration-impairing effects of luteoskyrin and rugulosin were not detected at the concentrations tested (max. 35 μM). The involvement of redox-reaction was not detected in the uncoupling effect of the quinone pigment, rubroskyrin.Spectroscopic study at various pHs revealed that rubroskyrin possessed a pK value within the range of physiological pH, suggesting that rubroskyrin is a weak acid-type uncoupler capable of conducting protons across mitochondrial inner membrane.

Mycotoxins Affecting Animals, Foods, Humans, and Plants: Types, Occurrence, Toxicities, Action Mechanisms, Prevention, and Detoxification Strategies—A Revisit

“…In animals, it is hepatotoxic and in vitro studies on myoblasts have shown that cyclochlorotine would interrupt the myofibrils to form alpha-actinin aggregates and islands of myosin [187,188]. P. islandicum also produces another mycotoxin known as luteoskyrin, which appears regularly in rice and has been shown to elevate the serum transaminases, damage the hepatocellular membrane, and cause lipid peroxidation in mice [172,189,190]. P. islandicum also produces rubroskyrin, which obstructs the mitochondrial respiration in rat livers [172,189,190].…”

“…P. islandicum also produces another mycotoxin known as luteoskyrin, which appears regularly in rice and has been shown to elevate the serum transaminases, damage the hepatocellular membrane, and cause lipid peroxidation in mice [172,189,190]. P. islandicum also produces rubroskyrin, which obstructs the mitochondrial respiration in rat livers [172,189,190]. P. islandicum also produces rugulosin, a hepatotoxin in animals [172,189,190].…”

The redox reaction and biotransformation of rubroskyrin, a modified bis-anthraquinone fromPenicillium islandicum sopp

“…Rubroskyrin is markedly less toxic than luteoskyrin (Umeda et al, 1974), though the in vitro toxicity to mitochondrial function is significantly stronger than that of luteoskyrin and rugulosin (Mori et al, 1996). The potency of mutagenic and antibacterial activities of rubroskyrin is diminished by rat liver microsomes (Stark et al, 1978).…”

“…Rubroskyrin, a cytotoxic and mutagenic anthraquinoid pigment produced by Penicillium islandicum Sopp (Takeda et al, 1973), has been shown to impair mitochondrial respiration in vitro (Mori et al, 1996) and to interact with the NADH dehydrogenase complex of the mitochondrial respiratory chain, resulting in the generation of an electron transport-shunt from NADHubiquinone oxidoreductase (complex I) to cytochrome c oxidase (complex IV) by its redox reaction (Mori et al, 1997). Luteoskyrin, the most toxic bis-anthraquinoid pigment produced by P. islandicum (Ghosh et al, 1977;Enomoto and Ueno, 1974;Uraguchi et al, 1972), is known to impair mitochondrial respiration and RNA synthesis (Ueno et al, 1964;Ueno et al, 1967), which are thought to be molecular mechanisms of its hepatotoxicity.…”

Taxonomic re-evaluation of species in <I>Talaromyces</I> section <I>Islandici</I>, using a polyphasic approach

“…Even though it has been classified as a mycotoxin, erythroskyrin was also reported to be an antitumor agent ( Kenkyusho 1983 ). Rubroskyrin and flavoskyrin are also classified as toxins ( Kawai et al 1984 , Mori et al 1996 ) and are produced by some sect. Islandici species.…”