Table 1.

Summary of the protective agents against organ toxicity of T-2.

Protective agents	Models	Dose and time	Organ toxicity	Effects	Mechanisms	References
Alfalfa meal	Rats	Alfalfa meal (5%, 12.5%, 20%) + T-2 (3 μg/g feed) for 2 weeks.	Gastrointestinal toxicity	-Antagonizing food refusal and growth inhibition toxicity in rats.	-Binding T-2 in gastrointestinal tract and thus promoting fecal excretion.	Carson and Smith (1983a)
RA	IPEC-J2 cells	Pre-incubated with RA (50 μmol/L) for 24 h; T-2 (5 nmol/L) for 48 and 72 h.		-Alleviating intestinal cell damage.	-Antioxidant; -Anti-inflammation.	Pomothy et al. (2020a)
BA	Mice	Pretreated with BA (0.25, 0.5, 1 mg/kg BW i.g.) for 2 weeks; T-2 (4 mg/kg BW i.p.) once.		-Improving the antioxidant capacity and the intestinal inflammatory response of the intestine; -Alleviating intestinal immune barrier dysregulation.	-Antioxidant; -Anti-inflammation.	Luo et al. (2020)
FWGE	IPEC-J2 cells	FWGE (1% and 2%) + T-2 (5 nmol/L) for 24 h.		-Improving cell viability and cell monolayer integrity.	-Antioxidant.	Pomothy et al. (2020b)
Bentonite	Rats	Pretreated with bentonite (5%, 7.5% or 10%) for 2 weeks; T-2 (3 μg/g feed) once.		-Overcoming the toxic symptoms of growth inhibition and food refusal in rats.	-Shortening the transit time of T-2 in the intestine.	Carson and Smith (1983b)
Smectite	Mice	T-2 was incubated with smectite for 24 h before oral administration; T-2 (1 mg/kg BW/d, p.o.); Smectite (2 g/kg/d).		-Protecting mice against T-2-induced disturbances of gastrointestinal transit.	-Smectite reinforced the natural defense of the gastric mucosa.	Fioramonti et al. (1987)
Mineral clays	Caco-2 cells	T-2 (100 μmol/L) + 0.1 mg/mL of each clay (diosmectite, montmorillonite, and illite) for 24 h.		-Restoring intestinal barrier permeability.	-Reversing T-2-induced reduction in the tight junction constituents claudin-3, claudin-4 and occludin expression and trans-epithelial electrical resistance.	Romero et al. (2016)
HSCAS	Broilers	0.05% HSCAS + T-2 (6.0 mg/kg feed) for 2 weeks.		-Reducing the toxicity of T-2 in broilers.	-Reducing T-2-induced toxicity in growth performance, nutrient digestibility, and small intestinal morphology.	Wei et al. (2019)
MycoRaid	Broilers	MycoRaid (1 or 3 g/kg feed) + T-2 (1 mg/kg feed) for 1–10 d.		-Improving broilers performance.	-Restoring feed consumption and body weight; -Increasing the concentration of total protein and albumin in the blood.	Riahi et al. (2021)
SeMet	Rabbits	Orally administered with SeMet (0.2, 0.4 and 0.6 mg/kg feed) for 21 d; On 17th d, each group began to take 0.4 mg/kg feed of T-2 orally/d for 5 d.		-Protecting the intestine from damage caused by T-2.	-Alleviating oxidative stress, jejunal inflammation; -Preserving the integrity of the intestinal barrier.	Liu et al. (2020)
FPH	Human colon cancer TC7 cells and Caco-2.	FPH (0.0625 mg/mL) + T-2 (60 nmol/L) for 24 h.		-Protecting against T-2-induced cytotoxicity.	-Improving cell viability.	Taroncher et al. (2021)
Prednisolone and hydrocortisone	Mice	Pretreated i.p. with 100 mg/kg BW of prednisolone or hydrocortisone for 3 d; T-2 (1.8 mg/kg BW, s.c.) for 4 d.		-Suppressing the lethal toxicity.	-Anti-inflammation.	Mutoh et al. (1988)
Dietary nucleotides	Male broiler chickens	Exposed T-2 (10 mg/kg feed) with nucleotides (2 g/kg feed) for 17 d.	Immunotoxicity	-Having beneficial effect on the immune system in T-2 intoxication.	-Reducing T-2-induced DNA fragmentation in spleen leukocytes.	Frankic et al. (2006)
Se	Mice	The sublethal dose of T-2.		-Asserting an important effect against the immunotoxic effects of T-2.	-Suppressing the T-2-induced reduction in peripheral blood B lymphocytes (CD19+) abundance.	Ahmadi et al. (2015)
SeMet	Rabbits	Orally administered with SeMet (0.2, 0.4 and 0.6 mg/kg feed) for 21 d. On 17th d, each group began to take 0.4 mg/kg BW of T-2 orally every day for 5 d.		-Attenuating T-2-induced immunotoxicity.	-Improving its antioxidant and anti-inflammatory capabilities in the spleen and thymus.	Zhang et al. (2022h)
Arginine	Chinese mitten crab	Pretreated with 3.17% arginine for 8 weeks; Injected with T-2 (1.5 mg/kg BW).		-Resistance to T-2-induced immune damage in the hepatopancreas.	-Increasing the antioxidant capacity.	Zhang et al. (2020a)
BA	Mice	Pretreated with BA (0.25, 0.5, or 1 mg/kg BW i.g.) for 2 weeks, T-2 (4 mg/kg BW single i.p.).		-Exerting the antioxidative and immunomodulatory activities of BA on spleen oxidative damage induced by T-2.	-Elevating the activities of antioxidant enzymes, reducing lipid peroxidation and ROS accumulation, and decreasing splenocyte apoptosis.	Kong et al. (2021)
				-Protecting the thymus against the oxidative damage challenged by T-2.	-Activating Nrf2 and suppressing the MAPK signaling pathway.	Zhu et al. (2020)
NAC	Neuroblastoma- 2a cells	Pretreated with NAC (5 mmol/L) for 2 h, followed by treatment with T-2 (20 ng/mL) for 24 h.	Neurotoxicity	-Reducing neurotoxicity.	-Inhibiting caspase activation and apoptosis.	Zhang et al. (2018)
	Mouse microglia BV2 cell line.	Pretreated with NAC at 2.5 mmol/L for 1 h, followed by co-treatment with T-2 at 2.5 ng/mL for additional 24 h.		-Reducing oxidative stress and apoptosis.	-Preventing ROS production and mitochondrial dysfunction; -Reducing mitochondrial transmembrane potential.	Sun et al. (2022)
BA	Mice	Pretreated with BA (0.25, 0.5, and 1.00 mg/kg BW) for 14 d; T-2 (4 mg/kg BW, single i.p.).		-Protecting against brain damage induced by T-2.	-Increasing the levels of the brain neurotransmitters dopamine, 5-hydroxytryptamine, and acetylcholine, thus improving cognitive function. -Enhanced antioxidant and anti-inflammatory capacity in the brain.	Huang et al. (2022b)
Minocycline	Mice	Injected with T-2 (4 mg/kg BW) + minocycline (50 mg/kg BW).		-Suppressing the neurotoxicity caused by T-2.	-Inhibiting microglia activation, thus improving T-2-induced learning and memory impairment and locomotor inhibition.	Li et al. (2023)
L-arginine	Mouse Leydig cells	Treated with T-2 (10 nmol/L) + L-arginine (0.25, 0.5, or 1.0 mmol/L) for 24 h.	Reproductive toxicity	-Ameliorating T-2–induced cytotoxicities.	-Elevating antioxidative ability.	Yang et al. (2018)
				-Ameliorated the testosterone levels decreased by T-2.	-Regulating the mRNA expression and activities of StAR.	Yang et al. (2019b)
				-Blocking T-2-induced apoptosis	-Regulating specific intracellular death-related pathways.	Zhang et al. (2020b)
	Mice	Pretreated with L-arginine (5, 15, 25 g/kg feed) for 7 d; T-2 (10 mg/kg BW/d i.p.) for 7 d.		-Protecting reproductive impairments induced with T-2.	-Improving semen quality and serum testosterone levels.	Zhang et al. (2019)
Melatonin	Bovine ovarian granulosa cells	-Pretreated with melatonin (100 μmol/L) for 12 h; HT-2 toxin 50 nmol/L for 24 h.		-Alleviating HT-2 toxin-induced cells damage.	-Having protective effects against mycotoxin-induced apoptosis and oxidative stress.	Yang et al. (2019a)
Quercetin	Porcine ovarian granulosa cells	Quercetin (100 ng/mL) + T-2 (100 ng/mL) for 24 h.		-Mitigating cellular oxidative damage due to T-2 exposure.	-Increasing the antioxidant capacity.	Capcarova et al. (2015)
BA	Mice	Pretreated orally with BA (0.25, 0.5, and 1.0 mg/kg feed/d) for 14 d, T-2 (4 mg/kg BW i.p.) once.		-Having protective effect of BA on T-2-induced testicular injury.	-Reducing the oxidative damage by the JAK2/STAT3 pathway.	Wu et al. (2019)
NAC	TM4 cells (The Sertoli cell line)	T-2 (4 nmol/L) + NAC (5 mmol/L) for 24 h.		-Relieving TM4 cell functional injury.	-Inhibiting low cell viability, oxidative stress and cell apoptosis caused by T-2.	Yang et al. (2021)
VE and Se	Bovine Leydig cells	100 nmol/L Se+10 nmol/L T-2; 100 μmol/L VE+10 nmol/L T-2; 100 nmol/L Se+100 μmol/L VE+10 nmol/L T-2 for 24 h.		-Ameliorating T-2-induced cytotoxicities.	-Preventing oxidative stress and DNA damage.	Yang et al. (2022)
Se	Rats	Pre-supplementation Se (0.5 and 2.5 mg/kg feed for 6 weeks); T-2 (3.8 mg/kg BW).	Hepatotoxicity	-Reducing mortality due to T-2.	-Se affected liver metabolism.	Kravchenko et al. (1990)
Se, VE, VC	Rats	Received Se (0.15 mg), VE (15 mg) and VC (6 mg) i.g. 16 h before the administration of T-2 (3.6 mg/kg BW orally a single dose).		-Alleviating liver injury.	-Reducing T-2-induced hepatic LPO and GSH depletion.	Rizzo et al. (1994)
Modified glucomannans and organic Se	Chicken	Mycosorb (1 g/kg feed) Sel-Plex (Se 0.3 mg/kg feed); T-2 (8.1 mg/kg feed for 21 d).		-Preventing T-2-induced oxidative stress damage and LPO in liver.	-Protecting against the detrimental effects of T-2 on the antioxidant defences in the chicken liver.	Dvorska et al. (2007)
SeMet	New Zealand rabbits	SeMet (0.2 mg/kg feed) for 21 d. On the 17th day, orally administered with T-2 (0.4 mg/kg BW) for 5 d.		-Improving T-2-induced liver injury.	-Inhibiting the mitochondrial- caspase apoptosis pathway.	Liu et al. (2021c).
CoQ10, VE	Mice	Gavage pretreatment with CoQ10 (6 mg/kg BW) and alpha-tocopherol (6 mg/kg BW) for 4 weeks. T-2 (1.8 or 2.8 mg/kg BW, single oral dose).		-Blocking T-2-induced hepatocyte death and GSH depletion.	-Reducting T-2-induced DNA damage in livers.	Atroshi et al. (1997)
Lycopene	Broiler chickens	T-2 (1.5 mg/kg BW/d) + Lycopene (25 mg/kg BW/d) for 7, 14 and 21 d.		-Alleviated oxidative damage in the liver of chickens fed T-2.	-Stopping GSH depletion in liver cells.	Leal et al. (1999).
Food indoles	Rats	Fed with 0.1% food indoles for 8 d; T-2 (0.8 mg/kg BW).		-Attenuating the hepatotoxicity of T-2.	-Elevating activity of microsomal carboxylesterase and UDP-glucuronosyltransferase, the key enzymes for detoxification of T-2.	Kravchenko et al. (2001)
HSCAS	Broilers	0.05% modified HSCAS adsorbent + T-2 (6.0 mg/kg feed) for 2 weeks.		-Blocking T-2-induced AST elevation and mitigating hepatotoxicity.	-Increasing surface area and might be able to increase adsorbing mycotoxins and avoid adsorbing the nutrients in feed.	Wei et al. (2019)
Arginine	Chinese mitten crab	Pretreated with 3.17% Arg for 8 weeks; Injected with T-2 (1.5 mg/kg BW).		-Alleviating T-2-induced hepatotoxicity.	-Enhancing the antioxidant capacity of Chinese mitten crab against oxidative damage to the hepatopancreas induced by T-2.	Zhang et al. (2020a)
YCWE and PYCW	Broilers	Contaminated diet containing T-2 (104 g/kg feed) + 0.2% YCWE or 0.2% PYCW.		-Improving the negative effects of T-2 on growth performance and liver function.		Kudupoje et al. (2022)
CC2	Mice	20% CC-2 formulation was applied on the exposed dorsal surface at 5, 15, 30 and 60 min after T-2 (11.8 mg/kg BW percutaneous exposure).		-Protecting mice from T-2-induced hepatic LPO; -Reducing mortality.		Agrawal et al. (2012a)
L-Carnitine	Rats, primary rat hepatocytes	Received L-carnitine (50 or 500 mg/kg i.p.) for 5 d, rat hepatocytes were isolated and treated with T-2 (640 ng/mL) for 2 h.		-Alleviating liver injury.	-Antioxidant properties, mitochondrial protection and inhibition of apoptosis.	Moosavi et al. (2016)
CA	Broiler chickens	1% CA-supplemented diet for 4 d; T-2 (2.0 mg/kg BW) oral administration for 4 d.		-Alleviating T-2-induced liver damage and the broiler mortality.	-Inducing the expression of FXR, thus reducing inflammatory and oxidative stress in hepatocytes.	Dai et al. (2020)
Curcumin and taurine	Rats	Administrated T-2 sublethal oral dose (0.1 mg/kg BW i.p.) for 2 months, followed by curcumin (80 mg/kg BW) and taurine (50 mg/kg BW) for 3 weeks.		-Ameliorating T-2-induced hepatotoxicity.	-Improving antioxidant capacity.	Al-Zahrani et al. (2023)
SeMet	Rabbits	Fed diets containing SeMet (0.2 mg/kg) for 21 d; On the 17th day, perfused with T-2 (0.4 mg/kg BW) for 5 d.	Nephrotoxicity	-Restoring kidney function.	-Reducing T-2-induced ROS and inflammatory factor levels.	Liu et al. (2021b)
Se	Mice	Pretreated with Se (0.2 mg/kg BW/d) for 2 h, then exposed to T-2 (1.0 mg/kg BW/d) for 28 d.		-Alleviating T-2-induced nephrotoxicity.	-Inhibiting ROS-mediated renal apoptosis.	Zhang et al. (2022f)
BA	Porcine kidney cells	Pretreated with BA (0.25, 0.5, and 1 μmol/L) for 24 h, continued with subsequent T-2 (1 μmol/L) for 24 h.		-Alleviating renal cytotoxicity.	-Ameliorating T-2-induced oxidative stress damage and apoptosis by increasing SOD, GSH-Px, and CAT activity and reducing intracellular ROS and MDA production.	Li et al. (2021)
	Mice	Pretreated with BA (0.25, 0.5, and 1 mg/kg BW i.g.) for 14 d; T-2 (4 mg/kg BW) was injected intraperitoneally at the 9th h after the last oral administration of BA.		-Protecting against renal damage.	-Attenuating oxidative stress and inflammation via Nrf2 pathway.	Huang et al. (2021).
Catalase and VC	Rat cardiomyocytes	T-2 (6.0 × 10−3 and 6.0 × 10−4 μmol/L) + VC (10 μg/mL) or catalase (10 U/mL) for 24 h.	Cardiomyopathy	-Improving the mitochondrial dysfunction under T-2 exposure.	-Antioxidant effects.	Ngampongsa et al. (2013)
Se	Primary cardiomyocytes	T-2 (0.25−1 μmol/L)		-Selenium deficiency lowered cytoprotective autophagy in the primary cardiomyocytes treated by T-2.	-The combination effects of selenium deficiency and T-2 on the development of Keshan disease.	Chen et al. (2019)
Methylprednisolone	Rats	Methylprednisolone (a total single dose of 40 mg/kg i.m.) was given immediately after T-2 (0.23 mg/kg s.c.).		-Showing a significant cardioprotective efficacy.	-Anti-inflammatory activity.	Jacevic et al. (2019)
Se	Chondrocytes	T-2 (0.001–2 mg/L).	Skeletal toxicity	-Partly antagonizing the inhibitory effects of T-2 on aggrecan.		Chen et al. (2006; Li et al. (2008)
				-Inhibiting aggrecan degradation in chondrocytes induced by T-2.
	An artificial cartilage model	Se (0.1 μg/mL) for 14 d; T-2 (1, 10 and 20 ng/mL).		-Having a protective role on chondrocytes.	-Preventing the decrease in type II collagen protein induced by T-2 in engineered cartilage.	Chen et al. (2011)
	Cultured chondrocytes	T-2 (5, 10, 20, 40 and 80 ng/mL) supplemented with Na2SeO3 (50, 100 and 150 ng/mL), and incubated for 6, 12, 24, 36 and 48 h.		-Reducing T-2-induced cytotoxicity.	-Promoting metabolic conversion of T-2.	Yu et al. (2017)
	Rats, primary epiphyseal chondrocytes	Administered with low Se (0.09 ng/g) and/or T-2 (100 ng/g BW per day) for 4 weeks to establish a KBD animal model.		-Inhibiting the progress of KBD.	-Reversing the effects of T-2 on chondrocyte injury.	Shi et al. (2021)
	Rats	Administered with T-2 (200 ng/g BW per day) for 4 weeks under the Se-deficient diet.		-Se-supplementation partially antagonized the inhibitory effects of T-2 in chondrocytes and cartilages.	-Low selenium induced matrix degradation.	Zhang et al. (2021a)
NAC	Chicken tibial growth plate chondrocytes	NAC (0.5 mmol/L) was co-administered with T-2 (5, 50, and 500 nmol/L) for 48 h.		-Protecting chicken growth plate chondrocytes.	-Reducing T-2-induced oxidative stress.	He et al. (2012)
Mycotoxin adsorbents: EGM, HSCAS, CMA	Broilers	The mycotoxins-contaminated feed containing T-2 (320.5 μg/kg) + 0.05% EGM or +0.2% HSCAS or + 0.1% CMA for 10, 21, 35 and 42 d.	Muscle toxicity	-Preventing the adverse effects on meat quality of mycotoxins to varying extents.	-Improving growth performance and nutritional retention in broilers due to mycotoxins.	Liu et al. (2011)
Quercetin	Shrimps	Quercetin (2.00 to 32.00 g/kg feed) or tea polyphenols or rutin + T-2 (4.80–24.30 mg/kg feed) for 20 d.		-Having the protective effect on T-2-induced muscle toxicity.	-Preventing abnormal changes in the target protein and muscle composition; -Reducing the degree of muscle protein deterioration.	Huang et al. (2022a)
Tea polyphenols and rutin				-Ameliorating the T-2-induced damage to muscle proteins.	-Increasing the sarcoplasmic and myofibrillar protein content and decreasing the alkali-soluble protein content.
Menthol	Mice	T-2 (2.97 mg/kg BW) for 72 h and 120 h; 0.25% and 0.5% menthol.	Skin toxicity	-Having the protective effect against T-2- induced skin toxicity in mice.	- Anti-inflammatory effect.	Rachitha et al. (2023)
CC-2	Mice	The subcutaneous application of 20% CC-2 within 5 and 15 min of treatment with T-2 (23.76 mg/kg BW topical percutaneous smearing).		-CC-2 may be an effective skin decontaminant against lethal topical exposure to T-2.		Agrawal et al. (2012a)
Quince seed	Rabbits	100 μg T-2 was dissolved in 12 μL methanol and applied on the shaved skin of rabbit for 2 d. Quince seed mucilage (15%).		-Showing more and better healing effects on dermal toxicity caused by T-2.		Hemmati et al. (2012)

p.o. = oral administration; s.c. = subcutaneous injection; i.g. = intragastrical administration; i.p. = intraperitoneal injection; i.m. = intramuscular injection; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BA = betulinic acid; BW = body weight; CA = cholic acid; CC-2 = N,N′-dichloro-bis (2,4,6-trichlorophenyl) urea; CMA = compound mycotoxin adsorbent; CoQ10 = coenzyme Q10; EGM = esterified glucomannan; FPH = fish protein hydrolysates; FWGE = fermented wheat germ extract; FXR = farnesoid X receptor; GSH = glutathione; GSH-Px = glutathione peroxidase; HSCAS = hydrated sodium calcium alumino silicate; IPEC-J2 = intestinal porcine epithelial cell line-J2 cells; JAK2 = Janus kinase 2; KBD = Kashin-Beck disease; LPO = lipid peroxidation; MAPK = mitogen-activated protein kinase; MDA = malondialdehyde; MycoRaid = A novel multicomponent MYC; NAC = N-acetylcysteine; Nrf2 = nuclear factor erythroid 2-related factor 2; RA = rosmarinic acid; ROS = reactive oxygen species; Se = selenium; SeMet = selenomethionine; SOD = superoxide dismutase; StAR = steroidogenic acute regulatory protein; STAT3 = signal transducer and activator of transcription 3; T-2 = T-2 toxin; VC = vitamin C; VE = vitamin E; YCWE = yeast cell wall extract.