4 research outputs found
Basic mechanisms of the cellular alterations in T-2 toxin poisoning: Influence on the choice and result of the therapy
T-2 mycotoxin, secondary metabolite of Fusarium fungi, is one of the most potent cytotoxic representatives of trichothecene mycotoxin type A. After ingestion, T-2 toxin affects actively dividing cells and irreversible post-mitotic cells. In our experiments, the best protective effects were produced by dexametasone (PI = 3.37) and different methylprednisolone formulations (PI = 2.43-2.64). Significant protective efficacy was shown by nimesulide (PI = 1.44) and N-acethyilcistein (PI = 1.29), but their values were higher in a combination with methylprednisolone (PI = 2.16-2.34). Radioprotector amifostine (WR-2721) expressed good protective effects (PI = 1.26) or/and different absorbent formulations, such as: activated charcoal (PI = 1.13) and various Min-a-zelĀ® powder compounds, which are a well known zeolite clinoptilolite absorbents. Among the five zeolite regimens investigated, only Min-a-zel PlusĀ® showed a significant protective effect (PI = 1.77). In summary, the steroidal anti-inflammatory drugs could be recommended as a regimen of choice for treatment of acute T-2 toxicosis while nonsteroidal anti-inflammatory compounds, different absorbent formulations and their combinations with antioxidants or radioprotectors could be important for the treatment of subacute and chronic T-2 toxin poisonings.T-2 mikotoksin, sekundarni metabolit gljivica iz roda Fusarium, jedan je od najtoksiÄnijih predstavnika trihotecenskih mikotoksina tipa A. Njegove osnovne osobine, prvenstveno velika stabilnost u prirodi, jeftina proizvodnja, teÅ”ka detekcija i joÅ” uvek nepostojanje adekvatnog antidota Äine ga veoma dobrim potencijalnim bojnim otrovom. Posle unoÅ”enja, u organizmu otrovane jedinke T-2 toksin se u Äelijama vezuje za receptore na ribozomima i pokreÄe seriju kaskadnih reakcija koje za posledicu imaju smanjenje stabilnosti gRNK i poveÄanu ekspresiju proinflamatornih gena koji su izmeÄu ostalog odgovorni za nastanak anoreksije, gubitak telesne mase imunosupresiju, autoimunih efekata i oÅ”teÄenje veÄine tkiva. ToksiÄno oÅ”teÄenje ciljnih organa, nastalo pod dejstvom T-2 toksina, posledica je njegovog citotoksiÄnog efekta na labilne Äelije i proinflamatornog efekta na stabilne Äelije u organizmu životinja i ljudi. S obzirom na napred iznete Äinjenice, jasno je Å”to je u naÅ”im istraživanjima najbolji terapijski efekat, kod akutnog trovanja T-2 toksinom, postignut primenom antiinflamatornih lekova steroidne strukture, prvenstveno deksametazona (ZI = 3,37) i razliÄitih oblika metilprednizolona (ZI = 2,43-2,64). Osim toga antiinflamatorni lekovi nesteroidne strukture ispoljili su znaÄajan terapijski efekat, nimesulid (ZI = 1,44) i N-acetlilcistein (ZI = 1,29), ali se njihovo zaÅ”titno dejstvo potencira u kombinaciji sa metilprednisolonom (ZI = 2,16-2,34). Terapijsku efikasnost ispoljili su radioprotektor amifostin (WR-2721) (ZI = 1,26) i/ili razliÄiti apsorbensi. Od primenjenih apsorbenasa, kao Å”to su aktivni ugalj (ZI = 1,13) i razliÄiti oblici Min-a-zel-aĀ®, najveÄi protektivni efekat ispoljio je Min-a-zel PlusĀ® oblik klinoptiolinskog zeolita (ZI = 1,77). Na osnovu prikazanih rezultata, a u skladu sa Äinjenicom da je citotoksiÄno i proinflamatorno dejstvo T-2 toksina u direktnoj srazmeri sa njegovom akutnom toksiÄnoÅ”Äu, u potpunosti je opravdano koriÅ”Äenje visokih doza antiinflamatornih lekova steroidne strukture u terapiji akutnog trovanja T-2 toksinom. Sa druge strane, u terapiji subakutnih ili hroniÄnih trovanja T-2 toksinom, preporuÄuje se upotreba antiinflamatornih lekova nesteroidne strukture, razliÄitih apsorbenasa, ili njihove kombinovane primene sa antioksidansima ili radioprotektorima
Histochemical evaluation of T-2 toxin-induced cardiotoxicity in rats: Semiquantitative analysis
In this study female Wistar rats were treated with T-2 toxin (1 LD50 0.23 mg/kg sc) and sacrificed on days 1, 3, 5, 7, 14, 21, 28 and 60 after the treatment. Control groups of rats were treated by saline (1 ml/kg 0.9% NaCl). At each time-schedule, control groups of animals were sacrificed, too. Pathohistological alterations of the heart were evaluated in whole visual fields stained by haematoxylin and eosin (HE), periodic acid- -Schiff's (PAS), Masson-Trichrom's (MT) and Giemsa (GIM) methods. The changes observed were scored by using semiquantitative grading scale. The heart alterations detected in T-2 toxin-treated animals ranged from focal parenchymal or hyaline degeneration (HE = 2.5 - 4.0; p lt 0.05 vs. control) to diffuse necrosis of muscle cells (HE = 5.0; p lt 0.05 vs. control and 1st day after T-2 treatment). The myofibrils were slightly PAS-positive during the first week of the study (PAS = 2.0 - 3.2; p lt 0.05 vs. control and 1st day after T-2 treatment), while a diffuse distribution of glycogen granules in endo- and perimisium were observed from day 21 to 60 in the whole heart' tissue (PAS = 4.0; p lt 0.05 vs. control and 1st day after T-2 treatment). Massive hemorrhagic foci associated with diffuse accumulation and degranulation of MCs were the most intensive from day 28 to 60 of the study (MT = 5.0; p lt 0.05 vs. control and 1st day after T-2 treatment). During the whole study period, irregular distribution of glycogen granules, intensity and total number of haemorrhages were in correlation with the degree of heart structural lesions, which showed the highest coefficient of correlation (r = 0.8750; p lt 0.001). Our results indicate that basic histohemical methods can be a useful tool for evaluation of T-2 toxin-induced cardiac damage, which is probably a result of complex inflammatory mechanisms, eventually leading to vascular lesions and myocardial necrosis, as well as for some potential cardioprotectors in the future.U ovom radu su ispitani toksiÄni efekti na srcu Wistar pacova akutno trovanih T-2 toksinom. Životinje, jednokratno tretirane T-2 toksinom u dozi od 0,23 mg/kg sc (1 LD50), žrtvovane su 1, 3, 5, 7, 14, 21, 28. i 60. dana posle aplikacije otrova. Kontrolne grupe životinja tretirane su fizioloÅ”kim rastvorom (1 ml/kg 0,9% NaCl) i žrtvovane u istim vremenskim intervalima. Procena patohistoloÅ”kih promena izvrÅ”ena je na uzorcima tkiva srca, bojenih standardnim histohemijskih metodama: hematoksilin i eozin (HE), Gimza (GIM), perjodna kiselina Schiff-ov reagens (PAS) i Masson trichrom (MT), primenom semikvantitativne analize. U srcu pacova tretiranih T-2 toksinom uoÄene su promene od fokalne parenhimatozne i hijaline degeneracije miofibrila (HE = 2,5-4,0; r lt 0,05 u poreÄenju sa kontrolom) do fokalne ili difuzne nekroze miÅ”iÄnih Äelija (HE = 5,0; r lt 0,05 u poreÄenju sa kontrolom i 1. danom posle aplikacije T-2 toksina). Tokom prve nedelje ispitivanja miofibrile su bile blago PAS-pozitivne (PAS = 2,0-3,2; r lt 0,05 u poreÄenju sa kontrolom i 1. danom posle aplikacije T-2 toksina), dok je difuzna distribucija granula glikogena u endo- i perimizijumu zapažena od 21. do 60. dana (PAS = 4,0; p lt 0,05 u poreÄenju sa kontrolom i 1. danom posle aplikacije T-2 toksina). Masivna hemoragiÄna polja, okružena mnogobrojnim inflamatornim Äelijama, naroÄito su izražena u periodu od 28. do 60. dana ispitivanja (MT = 5,0; p lt 0,05 u poreÄenju sa kontrolom i 1. danom posle aplikacije T-2 toksina). Tokom celog perioda ispitivanja, nepravilna distribucija granula glikogena, intenzitet krvarenja i ukupan broj mastocita su bili u korelaciji sa stepenom oÅ”teÄenja tkiva srca (r = 0,8750; p lt 0,001). Dobijeni rezultati su potvrdili ranije iznetu tezu da su kardiotoksiÄni efekti T-2 toksina verovatno rezultat kompleksnih inflamatornih mehanizama
Influence of the Green Tea Leaf Extract on Neurotoxicity of Aluminium Chloride in Rats
Aluminium may have an important role in the
aetiology/pathogenesis/precipitation of Alzheimer's disease. Because
green tea (Camellia sinensis L.) reportedly has health-promoting effects
in the central nervous system, we evaluated the effects of green tea
leaf extract (GTLE) on aluminium chloride (AlCl3) neurotoxicity in rats.
All solutions were injected into the cornu ammonis region 1 hippocampal
region. We measured the performance of active avoidance (AA) tasks,
various enzyme activities and total glutathione content (TGC) in the
forebrain cortex (FbC), striatum, basal forebrain (BFb), hippocampus,
brain stem and cerebellum. AlCl3 markedly reduced AA performance and
activities of cytochrome c oxidase (COX) and acetylcholinesterase (AChE)
in all regions. It decreased TGC in the FbC, striatum, BFb, hippocampus,
brain stem and cerebellum, and increased superoxide dismutase activity
in the FbC, cerebellum and BFb. GTLE pretreatment completely reversed
the damaging effects of AlCl3 on AA and superoxide dismutase activity,
markedly corrected COX and AChE activities, and moderately improved TGC.
GTLE alone increased COX and AChE activities in almost all regions. GTLE
reduces AlCl3 neurotoxicity probably via antioxidative effects and
improves mitochondrial and cholinergic synaptic functions through the
actions of (-)-epigallocatechin gallate and (-)-epicatechin, compounds
most abundantly found in GTLE. Our results suggest that green tea might
be beneficial in Alzheimer's disease. Copyright (c) 2013 John Wiley \&
Sons, Ltd.Ministry of Science of the Republic of Serbia {[}175058]; Ministry of
Defense of the Republic of Serbia {[}MMA/06-10/B.3