Betulinic Acid Attenuates Oxidative Stress in the Thymus Induced by Acute Exposure to T-2 Toxin via Regulation of the MAPK/Nrf2 Signaling Pathway

Abstract

T-2 toxin, the most toxic of the trichothecenes, is widely found in grains and feeds, and its intake poses serious risks to the health of humans and animals. An important cytotoxicity mechanism of T-2 toxin is the production of excess free radicals, which in turn leads to oxidative stress. Betulinic acid (BA) has many biological activities, including antioxidant activity, which is a plant-derived pentacyclic triterpenoid. The protective effects and mechanisms of BA in blocking oxidative stress caused by acute exposure to T-2 toxin in the thymus of mice was studied. BA pretreatment reduced ROS production, decreased the MDA content, and increased the content of IgG in serum and the levels of SOD and GSH in the thymus. BA pretreatment also reduced the degree of congestion observed in histopathological tissue sections of the thymus induced by T-2 toxin. Besides, BA downregulated the phosphorylation of the p38, JNK, and ERK proteins, while it upregulated the expression of the Nrf2 and HO-1 proteins in thymus tissues. The results indicated that BA could protect the thymus against the oxidative damage challenged by T-2 toxin by activating Nrf2 and suppressing the MAPK signaling pathway.

Betulinic Acid Alleviates Spleen Oxidative Damage Induced by Acute Intraperitoneal Exposure to T-2 Toxin by Activating Nrf2 and Inhibiting MAPK Signaling Pathways

“…The animals were kept in a 12 h/12 h light/dark environment with governable humidity (50–70%) and temperature (22–25 °C). The time and dosages of administration (BA and T-2 toxin) were decided according to previous reports [ 24 , 25 ].…”

“…MDA, a marker of lipid peroxidation, was detected following the thiobarbituric acid method [ 27 ]. The GSH level was detected using the dithiodinitrobenzoic acid method, SOD activity was assayed using the xanthine oxidase method, and T-AOC was determined using the colorimetric method, and all indexes were detected following the manufacturer’s protocols [ 25 ].…”

Betulinic Acid Ameliorates the T-2 Toxin-Triggered Intestinal Impairment in Mice by Inhibiting Inflammation and Mucosal Barrier Dysfunction through the NF-κB Signaling Pathway

“…The mice were acclimated in a temperature (22–25 °C) and humidity-controlled (50–70%) room in an adequately ventilated laboratory, with light and dark cycles of 12 h and free access to water and food. The administration time and the doses of T-2 toxin and BA were optimized on the basis of previous studies [ 57 , 58 ]. Mice were randomly assigned to six groups, namely, the control group, T-2 toxin only group, low-, medium- and high-dose BA (0.25, 0.5 or 1 mg/kg bw) and T-2 toxin cotreatment groups and the VE and T-2 toxin cotreatment group.…”

“…Then, 4 mg/kg T-2 toxin, dissolved in a mixed solution of alcohol and PBS (alcohol/PBS = 1:12.5), was injected intraperitoneally to induce oxidative damage, while the control group was injected with an equal volume of the mixed solution of alcohol and PBS. Serum samples were collected according to a previous method [ 58 ]. Mice were humanely sacrificed and the jejunum was quickly excised and stored at −80 °C until analysis.…”

“…The process of Western blot was conducted according to a previous method [ 58 ]. The total proteins of jejunum samples were received using a standard protocol by lysing tissues with RIPA buffer containing phenylmethanesulfonyl fluoride (PMSF).…”