Development of an L6 myoblast in vitro model of moniliformin toxicosis

Abstract

L6 myoblasts were used as an in vitro model to investigate the role of moniliformin and its interaction with monensin in turkey knockdown syndrome and sudden death syndromes in poultry. Cell viability and microscopic and ultrastructural alterations noted in L6 myoblasts cultured in the presence of moniliformin (0.0-0.3 microgram/microliter) were compared to those observed in parallel cultures also containing one of the following compounds: selenium (0-0.004 ng/microliter), thiamine (0-0.3 microgram/microliter), or pyruvate (0-0.46 microgram/microliter). Marked dilation of the RER, membranous whorls, glycogen deposition, membrane-bound cytoplasmic inclusions and necrosis were observed in myoblasts exposed to 0.03-0.30 microgram moniliformin/microliter medium. Supplementation of medium with thiamine and pyruvate, or selenium, provided significant protection to cells exposed to 0.0-0.3 microgram/microliter or 0.0-0.15 microgram moniliformin/microliter, respectively. Dose-dependent differences in protein and ATP production were not detected. Myoblasts grown in medium containing 0-0.15 microgram moniliformin/microliter and 7.5-50.0 microM A23187, beauvericin or monensin had degrees of cytotoxicity similar to parallel cultures receiving only an ionophore. L6 myoblasts were a useful model of moniliformin toxicosis. The findings of this study suggest cytotoxicity due to moniliformin in L6 myoblasts may be due in part to oxidative damage and altered pyruvate metabolism, and that moniliformin does not predispose myoblasts to ionophore toxicosis. This study supports the results of in vivo investigations in poultry that moniliformin and monensin do not act synergistically to induce knockdown or monensin toxicosis.

Evaluation of the genotoxicity of Fusarium mycotoxin moniliformin in human peripheral blood lymphocytes

“…In contrast, positive results have been obtained in plant [Styer and Cutler, 1984] and in primary cultures of rat hepatocytes [Knasmüller et al, 1997]. The cytotoxicity of MON has been demonstrated in various cell types [DombrinkKurtzman et al, 1993;Wu et al, 1995;Reams et al, 1996].…”

“…Knasmüller et al [1997] reported that MON causes chromosomal aberrations in primary cultures of rat hepatocytes. The cytotoxicity of MON has been demonstrated in various cells [Dombrink-Kurtzman et al, 1993;Wu et al, 1995;Reams et al, 1996].…”

“…Previous work has demonstrated increased ROS production following MON exposure [Reams et al, 1996]. It is well known that ROS can interact with biomolecules including DNA and causes DNA single or double strand breaks.…”

Evaluation of the genotoxicity of Fusarium mycotoxin moniliformin in human peripheral blood lymphocytes

“…In contrast, positive results have been obtained in plant [Styer and Cutler, 1984] and in primary cultures of rat hepatocytes [Knasmüller et al, 1997]. The cytotoxicity of MON has been demonstrated in various cell types [DombrinkKurtzman et al, 1993;Wu et al, 1995;Reams et al, 1996].…”

“…Knasmüller et al [1997] reported that MON causes chromosomal aberrations in primary cultures of rat hepatocytes. The cytotoxicity of MON has been demonstrated in various cells [Dombrink-Kurtzman et al, 1993;Wu et al, 1995;Reams et al, 1996].…”

“…Previous work has demonstrated increased ROS production following MON exposure [Reams et al, 1996]. It is well known that ROS can interact with biomolecules including DNA and causes DNA single or double strand breaks.…”

Mycotoxins: Producing Fungi and Mechanisms of Phytotoxicity

“…The toxicity of MON has been studied under in vitro and in vivo conditions. In vitro studies indicated an inhibition of multiple enzyme systems such as pyruvate dehydrogenase, transketolase, aldose reductase, glutathione peroxidase, and glutathione reductase [264][265][266][267][268]. Feeding studies with different avian species such as broiler chicks and ducklings using feed contaminated with MON resulted in symptoms such as acidosis and muscular weakness [269,270].…”

Fusarium mycotoxins: a review of global implications for animal health, welfare and productivity

“…Chicken macrophage viability may be reduced by exposure to T-2 tetraol, a derivative of T-2 toxin (Kidd et al, 1997). Other studies suggest that the cytotoxicity of MON in an L6 myoblast in vitro model arises partly from oxidative damage and altered pyruvate metabolism (Reams et al, 1996). In pig kidney cells, elevated sphingoid bases and complex sphingolipid depletion were identified as the basis of the cytotoxic action of FB 1 (Yoo et al, 1996).…”

Evaluation of the genotoxicity of Fusarium mycotoxin moniliformin in human peripheral blood lymphocytes

“…In contrast, positive results have been obtained in plant [Styer and Cutler, 1984] and in primary cultures of rat hepatocytes [Knasmüller et al, 1997]. The cytotoxicity of MON has been demonstrated in various cell types [DombrinkKurtzman et al, 1993;Wu et al, 1995;Reams et al, 1996].…”

“…Knasmüller et al [1997] reported that MON causes chromosomal aberrations in primary cultures of rat hepatocytes. The cytotoxicity of MON has been demonstrated in various cells [Dombrink-Kurtzman et al, 1993;Wu et al, 1995;Reams et al, 1996].…”

“…Previous work has demonstrated increased ROS production following MON exposure [Reams et al, 1996]. It is well known that ROS can interact with biomolecules including DNA and causes DNA single or double strand breaks.…”

Mycotoxins: Producing Fungi and Mechanisms of Phytotoxicity

“…The toxicity of MON has been studied under in vitro and in vivo conditions. In vitro studies indicated an inhibition of multiple enzyme systems such as pyruvate dehydrogenase, transketolase, aldose reductase, glutathione peroxidase, and glutathione reductase [264][265][266][267][268]. Feeding studies with different avian species such as broiler chicks and ducklings using feed contaminated with MON resulted in symptoms such as acidosis and muscular weakness [269,270].…”

Fusarium mycotoxins: a review of global implications for animal health, welfare and productivity

“…Chicken macrophage viability may be reduced by exposure to T-2 tetraol, a derivative of T-2 toxin (Kidd et al, 1997). Other studies suggest that the cytotoxicity of MON in an L6 myoblast in vitro model arises partly from oxidative damage and altered pyruvate metabolism (Reams et al, 1996). In pig kidney cells, elevated sphingoid bases and complex sphingolipid depletion were identified as the basis of the cytotoxic action of FB 1 (Yoo et al, 1996).…”

Evaluation of the genotoxicity of Fusarium mycotoxin moniliformin in human peripheral blood lymphocytes

“…In contrast, positive results have been obtained in plant [Styer and Cutler, 1984] and in primary cultures of rat hepatocytes [Knasmüller et al, 1997]. The cytotoxicity of MON has been demonstrated in various cell types [DombrinkKurtzman et al, 1993;Wu et al, 1995;Reams et al, 1996].…”

“…Knasmüller et al [1997] reported that MON causes chromosomal aberrations in primary cultures of rat hepatocytes. The cytotoxicity of MON has been demonstrated in various cells [Dombrink-Kurtzman et al, 1993;Wu et al, 1995;Reams et al, 1996].…”

“…Previous work has demonstrated increased ROS production following MON exposure [Reams et al, 1996]. It is well known that ROS can interact with biomolecules including DNA and causes DNA single or double strand breaks.…”

Mycotoxins: Producing Fungi and Mechanisms of Phytotoxicity

“…The toxicity of MON has been studied under in vitro and in vivo conditions. In vitro studies indicated an inhibition of multiple enzyme systems such as pyruvate dehydrogenase, transketolase, aldose reductase, glutathione peroxidase, and glutathione reductase [264][265][266][267][268]. Feeding studies with different avian species such as broiler chicks and ducklings using feed contaminated with MON resulted in symptoms such as acidosis and muscular weakness [269,270].…”

Fusarium mycotoxins: a review of global implications for animal health, welfare and productivity

“…Chicken macrophage viability may be reduced by exposure to T-2 tetraol, a derivative of T-2 toxin (Kidd et al, 1997). Other studies suggest that the cytotoxicity of MON in an L6 myoblast in vitro model arises partly from oxidative damage and altered pyruvate metabolism (Reams et al, 1996). In pig kidney cells, elevated sphingoid bases and complex sphingolipid depletion were identified as the basis of the cytotoxic action of FB 1 (Yoo et al, 1996).…”