Abstract
T-2 toxin is a mycotoxin that has harmful effects on the immune system and cognitive function. Betulinic acid (BA) is a plant-derived pentacyclic lupane-type triterpenoid which possesses a wide spectrum of bioactivities. The study was aimed to explore whether BA has a protective effect on cognitive impairment and oxidative stress caused by T-2 toxin. BA was suspended in 1% soluble starch by continuous intragastric administration for 14 days, then the brain damage in mice was induced by a single intraperitoneal injection of T-2 toxin (4 mg/kg). It was found that BA alleviated the reduction of discrimination index in T-2 toxin-treated mice, and enhanced dopamine (DA), 5-hydroxytryptamine (5-HT), and acetylcholine (ACH) levels of brain neurotransmitter. Meanwhile, BA pretreatment ameliorated oxidative stress through increase of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione (GSH) levels, and inhibition of the generation of reactive oxygen species (ROS) and malondialdehyde (MDA) in the brain of mice exposed to T-2 toxin. Moreover, BA reduced brain hemorrhage and ecchymosis, improved the mitochondrial morphology, enriched the number of organelles, and inhibited cell apoptosis in brain challenged with T-2 toxin. Furthermore, BA inhibited mRNA expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) as well as enhanced mRNA expression of anti-inflammatory cytokine such as IL-10 in the brain of T-2 toxin-triggered mice. Therefore, BA could improve the cognitive function, enhance the antioxidant capacity, and inhibit the secretion of proinflammatory cytokines in brain, thereby playing a preventive and protective role against brain damage caused by T-2 toxin.
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Funding
We are grateful for the financial support from the Special Funds for Construction of Innovative Provinces in Hunan Province, China (Grant No. 2020NK2032), the Natural Science Foundation of Hunan Province, China (Grant No. 2020JJ4368), and the Innovation Research and Development Project of Hunan Development and Reform Commission (Grant No. 202114).
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You Huang: data curation, methodology, roles/writing — original draft, writing — review and editing. Zihan Zhu: data curation, roles/writing — original draft, writing — review and editing. Chenxi Luo: data curation, methodology. Chaoyang Ma: data curation, methodology. Li juan Zhu: data curation, methodology. Li Kong: data curation, methodology. Rongfang Li: methodology. Jing Wu: conceptualization, resources. Zhihang Yuan: conceptualization, resources. Jine Yi: conceptualization, funding acquisition, project administration, resources, supervision, validation, roles/writing — original draft, writing — review and editing.
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Huang, Y., Zhu, Z., Luo, C. et al. Betulinic acid attenuates cognitive dysfunction, oxidative stress, and inflammation in a model of T-2 toxin-induced brain damage. Environ Sci Pollut Res 29, 52098–52110 (2022). https://doi.org/10.1007/s11356-022-19498-z
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DOI: https://doi.org/10.1007/s11356-022-19498-z