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 lt 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 lt 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.

Cilj ovog rada je bio da se ispitaju efekti metilprednizolona (solubilni oblik, Lemod-solu®), nimesulida, N-acetilcisteina (Fluimucil®) i njihovih kombinacija kod pacova tretiranih sa 1,0 LD50 (0,23 mg/kg) trihotecenskog mikotoksina T-2. Antidotski efekat je ispitivan praćenjem njihovog uticaja na opšte stanje, 24-voro časovno preživljavanje, telesnu masu, potrošnju hrane i vode i patohistološke promene u digestivnom traktu tokom 4 nedelje, kod pacova, soj Wistar, kojima je jednokratno aplikovan T-2 toksin. Najveći zaštitni efekat ispoljio je metilprednizolon (2,43). Gubitak telesne mase, tokom prvih 7 dana ustanovljen je samo u T-2 toksin grupi. Tokom čitavog eksperimenta, u grupama trovanih pacova koji su štićeni metilprednizolonom ili metilprednizolonom i nimesulidom, ustanovljeno je značajno povećanje (p lt 0,001) telesne mase, potrošnje hrane i vode, u poređenju sa T-2 toksin gropom. Na kraju ispitivanog perioda, N-acetilcistein, nimesulid i njihova kombinacija obezbedili su takođe porast (p lt 0,05) telesne mase, potrošnje hrane i vode u poređenju sa T-2 toksin grupom. Znaci hemoragične dijateze i nekroza epitelnih žlezdica digestivnog trakta uočeni su u T-2 toksin grupi. Blage histološ ke promene bile su prisutne u digestivnom traktu trovanih pacova tretiranih nimesulidom, N-acetilcisteinom i njihovom kombinacijom. Histološka građa digestivnog trakta trovanih pacova koji su štićeni metilprednizolonom i nimesulidom, a posebno sa metilprednizolonom bila je slična kao u kontrolnoj grupi. Prikazani rezultati jasno ukazuju da je metilprednizolon, dobro poznat anti-inflamatorni i imunosupresivni lek, ispoljio najbolji zaštitni efekat kod pacova akutno trovanih T-2 toksinom.