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

Abstract

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

Antidotal Potency of the Novel, Structurally Different Adsorbents in Rats Acutely Intoxicated with the T-2 Toxin

“…Consistent with our previously published results, the T-2 toxin certainly leads to acute gastric mucosal damage [ 20 , 45 ]. The calculated LD 50 value of 1.67 mg/kg p.o.…”

“…was also in agreement with the data of other authors, verifying that its acute toxicity, depending on the animal species and application mode, was in an exceedingly wide range (i.e., 0.5–10.5 mg/kg) [ 3 , 10 , 46 ]. Additionally, when the T-2 toxin was administered orally, gastric damage occurred directly by toxic influence on the tunica mucosa , and partially by indirect excretion of its toxic metabolites from the hepatobiliary system [ 20 , 29 , 47 ].…”

“…In humans and animals, the T-2 toxin causes general signs of the so-called shock-like syndrome, accompanied with emesis, lowered weight gain, lethargy, bloody diarrhea, gastric and intestinal disorders, haemorrhaging, immunosuppression, cardiomyopathy, and finally death [ 13 , 14 , 15 , 16 , 17 , 18 ]. Furthermore, similarly to acute radiation syndrome [ 19 , 20 , 21 ], inflammatory reaction, caused by the T-2 toxin, is a consequence of phospholipase A2 activation, successive prostaglandins, and reactive oxygen species (ROS) production [ 15 , 22 , 23 ]. Intensive accumulation of ROS may lead to DNA damage, protein oxidation, and lipid peroxidation [ 24 , 25 , 26 ].…”

“…As mentioned earlier, these intensive gastric injuries are not only thanks to a local toxic effect [ 9 , 20 ], but to biliary excretion and enterohepatic recirculation of the T-2 and HT-2 toxins as well, [ 15 , 21 ] causing generalized toxic effects [ 34 ]. By providing the previously demonstrated mechanism of gastric toxicity induced by the T-2 toxin, an approach that supports the use of adsorbents seems to be rational.…”

Efficacy of T-2 toxin detoxifying agent in broiler chickens

“…One of the most important targets in T-2 toxicosis is the digestive tract (Ja}evi} et al, 2010). In our study, changes in the intestine were directly connected to T-2 toxin presence in the feed, as a consequence of inhibited proliferation of rapidly dividing cells.…”