A possible protective role for reduced glutathione in aflatoxin B1 toxicity: Effect of pretreatment of rats with phenobarbital and 3-methylcholanthrene on aflatoxin toxicity

Mgbodile, Marcel U.K.; Holscher, Myron A.; Neal, Robert A.

doi:10.1016/0041-008x(75)90181-7

Cited by 79 publications

(10 citation statements)

References 14 publications

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“…The results of the studies reported here suggest that glutathione is not involved in reducing the toxicity of rubratoxin B. Although pretreatment in rats with diethyl maleate, which depletes hepatic glutathione (Boyland and Chasseaund, 1969), markedly increases the hepatotoxicity of aflatoxin (Mgbodile et al, 1975), the present study shows that similar pretreatment in mice does not alter rubratoxin B lethality. Pretreatment with cysteine, a precursor of glutathione, also failed to protect against rubratoxin B lethality.…”

Section: Discussioncontrasting

confidence: 55%

Structural role of an unsaturated lactone in acute toxicity of rubratoxin B isolated from Penicillium rubrum

Feng

Wong

Evans

1988

Phytotherapy Research

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Rubratoxin B is a substituted higher homolog of byssochlamic acid in which the ethyl group is replaced by a six-membered ring containing an unsaturated lactone. Hydrogenation of the unsaturated lactone greatly reduces the acute toxicity of the compound. The acute median lethal doses of rubratoxin B and hydrogenated rubratoxin in male mice were 5.6 and 31 mg/kg, respectively. Pretreatment with phenobarbital (60mg/kgX4 days) or with SKF 525A (40mg/kg) failed to significantly alter the toxicity of either compound. Histopathological examination of mice treated witb rubratoxin B (3.5 mg/kg) revealed areas of hepatic zonal necrosis and marked necrosis of kidney tubules. No necrosis was observed in mice treated with hydrogenated rubratoxin (20 mglkg) Hepatic microsomal mixed function oxidase activity was significantly reduced in mice pretreated with rubratoxin B (0.5 mg/kg X 4 days), while pretreatment with hydrogenated rubratoxin (2.5 mg/kg X 4 days) failed to depress microsomal activity. Our studies document the requirement of an alpha, beta unsaturated lactone ring for rubratoxin B toxicity. Based on the results from these studies the mechanism for rubratoxin B induced toxicity is postulated to be due to its electrophilic properties and subsequent alkylating activity.K e y w o r k Rubratoxin B; unsaturated lactones; toxicity; histopathology.

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Section: Discussioncontrasting

confidence: 55%

Structural role of an unsaturated lactone in acute toxicity of rubratoxin B isolated from Penicillium rubrum

Feng

Wong

Evans

1988

Phytotherapy Research

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“…Furthermore, Sullivan et al (1978) documented that the addition of yeast to a aflatoxin-containing diet causes an increase in enzymes that modify the aflatoxin effects. The importance and potential of enzymes produced by certain microorganisms to decontaminate aflatoxicosis was documented by Mgbodile et al (1975), and later confirmed by Dalvi & McGowan (1984), who concluded that enzymes can stimulate the bio-transformation of a few toxins in vivo, thus altering the duration and intensity of the toxic effects.…”

Section: Tre Atmentmentioning

confidence: 90%

Thermolysed and active yeast to reduce the toxicity of aflatoxin

Baptista

Horii

Calori‐Domingues

et al. 2002

Sci. agric. (Piracicaba, Braz.)

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Aflatoxins are hepatotoxic metabolites produced by Aspergillus flavus and A. parasiticus on a number of agricultural commodities. This research was carried out to evaluate the ability of thermolysed and active Saccharomyces cerevisiae to attenuate liver damage caused by aflatoxin. Diets were prepared containing 0 aflatoxin; 400 mug kg-1 aflatoxin; 400 mug kg-1 aflatoxin plus 1% of dehydrated active yeast, and 400 mug kg-1 aflatoxin plus 1% of thermolysed yeast. A bioassay with Wistar rats was conducted for 28 days, and body organs were weighted and analyses of the liver tissue of the animals were performed. The relative weight of heart, kidneys and liver from animals submitted to the different treatments did not show any difference, and liver tissue of animals feeding on the aflatoxin-free diet was adopted as a toxicity-free pattern. Hepatic tissue of animals feeding on diets containing 400 mug kg-1 aflatoxin or the diet supplemented with 1% thermolysed yeast showed clear signs of toxicity and damage. Hepatic tissue of animals feeding on the diet containing 1% of dehydrated active yeast showed less toxicity signs and damage than those receiving the diet containing 400 mug kg-1 aflatoxin. Active, dehydrated yeast had the ability to reduce toxic effects caused by aflatoxin, but thermolysed yeast was not able to alleviate the effects of aflatoxin toxicity.

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“…Some other drugs, such as cyclophosphamide[2021] and acetaminophen,[2223] are known to produce toxic metabolites that are electrophilic in nature. Apart from drugs, some other chemicals such as butylated hydroxyanisole[23] and carcinogens such as aflatoxin[24] are also known to produce toxic metabolites that are electrophilic in nature. Presence of such toxic metabolites has been reported in ascites fluid.…”

Section: Discussionmentioning

confidence: 99%

Cysteine supplementation mitigates the toxicity associated with antitumor therapy of Ehrlich’s ascites fluid adsorbed over protein a containing Staphylococcus aureus cowan I^†

Verma

Singh

Mallick³

et al. 2019

J Pharm Bioall Sci

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Introduction: Previously, we have reported the amelioration of ad-AF induced hepatotoxicity with the exogenous supplementation of glutathione (GSH) without compromising the anti-tumor effect of ad-AF in ascites tumor model of mice with transplantable Ehrlich’s Ascites Tumor cells. Cellular uptake of glutathione (GSH) has its own limitations, therefore exogenous supplementation of L-cysteine (Cys) was tried to reduce the toxicity of ad-AF by providing –SH contents without compromising the anti-tumor property of adsorbed ascites fluid (ad-AF). Results: A significant increase in mean survival time (MST) of tumor bearing mice from 18.1 days to 32.9 days with exogenous supplementation of Cys was observed. Cys supplementation did not alter decline in body-weight gain, tumor cell counts as well as decrease in the viability of tumor cells in ascites tumor bearing animals. Similarly, Cys has been helpful to restore the hepatic –SH contents upto the levels of –SH content in tumor control group. The exogenous supplementation of Cys along with ad-AF has been helpful to restore the decline in the activities of phase-I and enhanced levels of glutathione-S-transferase (GST). The changes in the activities of different enzymes of phase-I and phase-II indicate the reduction in toxic insult induced by the therapeutic material (ad-AF). However, ad-AF treatment could not prevent tumor bearers from natural death due to tumor progression but significantly reduced the rate of tumor progression. Conclusions: Our study suggests that exogenous supplementation of Cys alongwith ad-AF could have a potential to be developed as a modality for the treatment of ascites tumor at least at experimental level.

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A possible protective role for reduced glutathione in aflatoxin B1 toxicity: Effect of pretreatment of rats with phenobarbital and 3-methylcholanthrene on aflatoxin toxicity

Cited by 79 publications

References 14 publications

Structural role of an unsaturated lactone in acute toxicity of rubratoxin B isolated from Penicillium rubrum

Structural role of an unsaturated lactone in acute toxicity of rubratoxin B isolated from Penicillium rubrum

Thermolysed and active yeast to reduce the toxicity of aflatoxin

Cysteine supplementation mitigates the toxicity associated with antitumor therapy of Ehrlich’s ascites fluid adsorbed over protein a containing Staphylococcus aureus cowan I^†

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A possible protective role for reduced glutathione in aflatoxin B1 toxicity: Effect of pretreatment of rats with phenobarbital and 3-methylcholanthrene on aflatoxin toxicity

Cited by 79 publications

References 14 publications

Structural role of an unsaturated lactone in acute toxicity of rubratoxin B isolated from Penicillium rubrum

Structural role of an unsaturated lactone in acute toxicity of rubratoxin B isolated from Penicillium rubrum

Thermolysed and active yeast to reduce the toxicity of aflatoxin

Cysteine supplementation mitigates the toxicity associated with antitumor therapy of Ehrlich’s ascites fluid adsorbed over protein a containing Staphylococcus aureus cowan I†

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Cysteine supplementation mitigates the toxicity associated with antitumor therapy of Ehrlich’s ascites fluid adsorbed over protein a containing Staphylococcus aureus cowan I^†