Effects of radioprotective compounds and anti-inflammatory agents on the acute toxicity of trichothecenes

Mutoh, Atsushi; Ueno, Yoshio

doi:10.1016/0378-4274(88)90158-0

Cited by 10 publications

(10 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the degree of intensity and quality of these pathohistological changes was similar to the ones observed in the poisoned rats protected with methylprednisolone and their combinations with nimesulide and N-acetylcysteine described, but the intensity of these histological changes were stronger. These results corroborate the existence of the antidotal efficacy of prednisolone and dexamethasone in mice (Mutoh et al, 1988) and of dexamethasone in rats poisoned with T-2 toxin (Tremel et al, 1985). Our result is probably a consequence of the fact that even the soluble form of methylprednisolone acts long enough to cover the peak of the T-2 toxin harmful effects.…”

Section: Discussionsupporting

confidence: 92%

Gastroprotective effects of novel antidotal combination in rats acutely poisoned by T-2 toxin

Jacević¹,

Rеsаnоvić²,

Bočarov-Stančić³

et al. 2010

Acta vet. (Beogr.)

View full text Add to dashboard Cite

The purpose of this experiment was to evaluate the antidotal potencies of methylprednisolone (soluble form, Lemod-solu®), nimesulide, N-acetylcysteine (Fluimucil®) and their combinations in rats treated with 1.0 LD50 (0.23 mg/kg) of trichothecene mycotoxin, T-2 toxin. Their antidotal efficacy was investigated by monitoring their effects on general condition, 24-hour-survival, body weight gain, food and water consumption and pathohistological changes in the gut of Wistar rats acutely treated with a single injection of T-2 toxin during a 4-week period. The highest protective index was obtained with methylprednisolone (2.43). Initial loss of body weight (after first 7 days) was found only in T-2 toxin group. During the whole experiment, in poisoned rats protected by methylprednisolone or methylprednisolone and nimesulide, a significant increase (p<0.001) in body weight gain, food and water consumption in comparison with T-2 toxin group was found. At the end of the experiment, N-acetylcysteine, nimesulide and their combination assured higher (p<0.05) weight gain, food and water consumption in comparison with T-2 toxin group. Signs of hemorrhagic diathesis and necrosis of the gut crypt epithelium and lymphoid tissues were found in the T-2 toxin group. Some of these histological alterations were presented in the gut of poisoned rats treated by nimesulide, Nacetylcysteine and their combination. The gut of T-2 toxin rats treated with a combination of methylprednisolone and nimesulide and especially methylprednisolone alone had a histological structure similar to the control group. These results clearly show that methylprednisolone, a well-known anti-inflammatory and immunosuppressive drug, exerts the best antidotal effect against T-2 toxin intoxication in rats

show abstract

Section: Discussionsupporting

confidence: 92%

Gastroprotective effects of novel antidotal combination in rats acutely poisoned by T-2 toxin

Jacević¹,

Rеsаnоvić²,

Bočarov-Stančić³

et al. 2010

Acta vet. (Beogr.)

View full text Add to dashboard Cite

show abstract

“…With a dose of 0.75 mg T-2 toxirdkg, administered intravenously (iv), dexarnethasone (1.6 mg/kg, iv) enhances survival rate of rats, but with T-2 toxin in a lethal dose of 1 mg/kg, only prolongation of the survival time could be observed. These protective effects of dexamethasone (with doses ranging from 2-50 mg/kg) in acute T-2 toxicosis were confirmed by other studies [Shohami et al, 1987;Poppenga et al, 1987a;Poppenga et al, 0 1994 Wiley-Liss, Inc. 1987b; Ryu et al, 1987;Mutoh et al, 1988;Fricke and Jorge, 199 I]. Furthermore, superactivated charcoal significantly enhanced survival rate in orally-induced lethal T-2 toxicosis [Buck and Bratich, 1987;Galey et al, 19871 and prevented morphological lesions [Bratich et al, 19901.…”

Section: Introductionsupporting

confidence: 81%

Influence of glucocorticoids and activated charcoal on the lethality of rats after acute poisoning with T‐2 toxin, diacetoxyscirpenol, or roridin A

1994

View full text Add to dashboard Cite

Lethal doses of the trichothecene mycotoxins T-2 toxin (1.5 mg/kg), diacetoxyscirpenol (DAS; 2.3 mg/kg) or roridin A (1.3 mg/kg) were intravenously administered to rats. When rats were treated with either activated charcoal (Superchar liquid, Norit A; 1 g/kg, po) or dexamethasone (8 mg/kg, iv) 30 min after poisoning with one of the trichothecenes, lethality was only marginally reduced. However, when the combination of activated charcoal (Superchar liquid or Norit A) and dexamethasone was administered, the survival rate of animals after 30 days was significantly enhanced by up to 50%. Comparison between 2 preparations of activated charcoal, Norit AR with a surface area of 1,000 m2/g and Superchar liquidR with a surface area of 3,000 m2/g, each in combination with dexamethasone, revealed no difference in their therapeutic efficacy. Prednisolone (60 mg/kg) was as effective as dexamethasone (8 mg/kg), each administered with activated charcoal, in preventing death in acute T-2 toxicosis.

show abstract

“…In this study, an intravenous dose of 0.75 mg/kg T-2 toxin killed two thirds of rats, but administration of dexamethasone (1.6 mg/kg intravenously) shortly before or after the T-2 toxin resulted in a 4-fold reduction in lethality, and particularly reduced lung oedema and diarrhroea (presumably indicative of gastrointestinal toxicity). This finding has also been confirmed in mice, where both prednisolone and hydrocortisone pretreatments reduced T-2 toxin lethality [Mutoh et al, 1988]. Additionally, both corticosterone and dexamethasone enhance the toxicity of vitamin D in rats [Kunitomoet al, 1989].…”

Section: General Toxicitymentioning

confidence: 81%

“…Glucocorticoids are a widely prescribed class of drugs and are often coprescribed with other drugs. The findings that drug tolerance can be affected by these steroids may provide practical benefits in identifying interactions, or ameliorating the toxicity resulting from, exposure to a variety of natural and synthetic chemicals, as has been most clearly demonstrated in animal models with the tricothecene mycotoxins by Tremel et al [1985], Mutoh et al [1988], and Hunder etal. [1994].…”

Section: Discussionmentioning

confidence: 99%

Glucocorticosteroid interactions with natural toxins: A mini review

Harvey,

Healing,

Rees

et al. 1994

Natural Toxins

View full text Add to dashboard Cite

A growing area of research in pharmacology and toxicology is concerned with the role of adrenal glucocorticosteroids (predominantly corticosterone in rats and mice, and cortisol in humans) in modulating toxicological responses. These steroids are secreted from the adrenal cortex, and in laboratory rodents secretion occurs particularly in response to stressful environmental change or noxious challenge, which can include a toxic insult. Glucocorticoids have profound biochemical effects in diverse tissues (e.g., inhibition of DNA and RNA synthesis; effects on carbohydrate metabolism, protein catabolism, and immunosuppression, and anti‐inflammatory effects). Given this range of pharmacological actions of glucocorticoids, effects on the response and tolerance to a toxic insult can be hypothesised. Indeed, it is now becoming clear that the toxicological response to a toxin can be modulated by pretreatment with, or coadministration of, natural glucocorticosteroids or their synthetic analogues. As achieving the maximum tolerated dose (MTD) in an experimental animal, whether via a natural toxin or a synthetic chemical, can be stressful, the implications of these findings are far reaching. This review is intended to illustrate the principle that the toxicological responses to natural toxins (e.g., kainic acid, aflatoxin B1, trichothecenes) can be modulated by corticosterone and other natural and synthetic glucocorticosteroids. Particular emphasis is given to neurotoxicity and hepatotoxicity in laboratory rodent models, but nephrotoxicity and cardiotoxicity, of which there are fewer studies, are also covered. Glucocorticoids can both enhance toxicity or protect against toxicity, and the direction of the effect depends on the target organ, the particular steroid, the properties of the toxin, and the temporal relationship of the coadministration regime.

show abstract

Effects of radioprotective compounds and anti-inflammatory agents on the acute toxicity of trichothecenes

Cited by 10 publications

References 13 publications

Gastroprotective effects of novel antidotal combination in rats acutely poisoned by T-2 toxin

Gastroprotective effects of novel antidotal combination in rats acutely poisoned by T-2 toxin

Influence of glucocorticoids and activated charcoal on the lethality of rats after acute poisoning with T‐2 toxin, diacetoxyscirpenol, or roridin A

Glucocorticosteroid interactions with natural toxins: A mini review

Contact Info

Product

Resources

About