Gruber-Dorninger Christiane, Faas Johannes, Doupovec Barbara, Aleschko Markus, Stoiber Christian, Höbartner-Gußl Andreas, Schöndorfer Karin, Killinger Manuela, Zebeli Qendrim, Schatzmayr Dian
BIOMIN Research Center, BIOMIN Holding GmbH, 3430 Tulln, Austria.
Institute of Animal Nutrition and Functional Plant Compounds, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
Toxins (Basel). 2021 Jan 22;13(2):84. doi: 10.3390/toxins13020084.
The mycotoxin zearalenone (ZEN) is a frequent contaminant of animal feed and is well known for its estrogenic effects in animals. Cattle are considered less sensitive to ZEN than pigs. However, ZEN has previously been shown to be converted to the highly estrogenic metabolite α-zearalenol (α-ZEL) in rumen fluid in vitro. Here, we investigate the metabolism of ZEN in the reticulorumen of dairy cows. To this end, rumen-fistulated non-lactating Holstein Friesian cows ( = 4) received a one-time oral dose of ZEN (5 mg ZEN in 500 g concentrate feed) and the concentrations of ZEN and ZEN metabolites were measured in free rumen liquid from three reticulorumen locations (reticulum, ventral sac and dorsal mat layer) during a 34-h period. In all three locations, α-ZEL was the predominant ZEN metabolite and β-zearalenol (β-ZEL) was detected in lower concentrations. ZEN, α-ZEL and β-ZEL were eliminated from the ventral sac and reticulum within 34 h, yet low concentrations of ZEN and α-ZEL were still detected in the dorsal mat 34 h after ZEN administration. In a second step, we investigated the efficacy of the enzyme zearalenone hydrolase ZenA (EC 3.1.1.-, commercial name ZEN, BIOMIN Holding GmbH, Getzersdorf, Austria) to degrade ZEN to the non-estrogenic metabolite hydrolyzed zearalenone (HZEN) in the reticulorumen in vitro and in vivo. ZenA showed a high ZEN-degrading activity in rumen fluid in vitro. When ZenA was added to ZEN-contaminated concentrate fed to rumen-fistulated cows ( = 4), concentrations of ZEN, α-ZEL and β-ZEL were significantly reduced in all three reticulorumen compartments compared to administration of ZEN-contaminated concentrate without ZenA. Upon ZenA administration, degradation products HZEN and decarboxylated HZEN were detected in the reticulorumen. In conclusion, endogenous metabolization of ZEN in the reticulorumen increases its estrogenic potency due to the formation of α-ZEL. Our results suggest that application of zearalenone hydrolase ZenA as a feed additive may be a promising strategy to counteract estrogenic effects of ZEN in cattle.
霉菌毒素玉米赤霉烯酮(ZEN)是动物饲料中常见的污染物,因其对动物的雌激素效应而广为人知。牛被认为对ZEN的敏感性低于猪。然而,此前已表明ZEN在体外瘤胃液中可转化为高雌激素代谢物α-玉米赤霉醇(α-ZEL)。在此,我们研究了ZEN在奶牛瘤网胃中的代谢情况。为此,给4头装有瘤胃瘘管的非泌乳荷斯坦弗里生奶牛一次性口服ZEN(5毫克ZEN溶于500克精饲料中),并在34小时内测量来自瘤网胃三个部位(瘤胃、腹囊和背垫层)的游离瘤胃液中ZEN及其代谢物的浓度。在所有三个部位,α-ZEL都是主要的ZEN代谢物,且检测到较低浓度的β-玉米赤霉醇(β-ZEL)。ZEN、α-ZEL和β-ZEL在34小时内从腹囊和瘤胃中消除,但在给予ZEN 34小时后,背垫中仍检测到低浓度的ZEN和α-ZEL。在第二步中,我们研究了玉米赤霉烯酮水解酶ZenA(EC 3.1.1.-,商品名ZEN,BIOMIN Holding GmbH,奥地利格茨多夫)在体外和体内瘤网胃中将ZEN降解为非雌激素代谢物水解玉米赤霉烯酮(HZEN)的功效。ZenA在体外瘤胃液中表现出高ZEN降解活性。当将ZenA添加到喂给装有瘤胃瘘管奶牛(n = 4)的受ZEN污染的精饲料中时,与给予不含ZenA的受ZEN污染的精饲料相比,所有三个瘤网胃隔室中ZEN、α-ZEL和β-ZEL的浓度均显著降低。给予ZenA后,在瘤网胃中检测到降解产物HZEN和脱羧HZEN。总之,瘤网胃中ZEN的内源性代谢由于α-ZEL的形成而增加了其雌激素效力。我们的结果表明,应用玉米赤霉烯酮水解酶ZenA作为饲料添加剂可能是抵消ZEN对牛雌激素效应的一种有前景的策略。