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. 2024 May 5;12(5):335.
doi: 10.3390/toxics12050335.

Tert-Butylhydroquinone Mitigates T-2-Toxin-Induced Testicular Dysfunction by Targeting Oxidative Stress, Inflammation, and Apoptosis in Rats

Yun Chen  1 , Xinke Zhang  2 , Shanshan Lan  1 , Shuping Liang  1 , Manyu Zhang  1 , Shuang Zhang  1 , Yijian Liu  1 , Li Li  2 , Hengxi Wei  2 , Shouquan Zhang  2
Affiliations

Tert-Butylhydroquinone Mitigates T-2-Toxin-Induced Testicular Dysfunction by Targeting Oxidative Stress, Inflammation, and Apoptosis in Rats

Yun Chen et al. Toxics. .

Abstract

Tert-butylhydroquinone (tBHQ) has emerged as a promising candidate for mitigating the adverse effects of T-2-induced reproductive toxicity. The protective effects of tBHQ on rat sperm quality, testicular injury, apoptosis, and inflammation induced by T-2 toxin exposure were investigated. Histopathological examination of testicular tissues revealed severe damage in the T-2-treated group, characterized by disorganized germ cell arrangement, thinning of the convoluted seminiferous tubule walls, and significant cellular necrosis. However, tBHQ administration, either as a preventive or therapeutic measure, mitigated this structural damage. Image analysis confirmed an increase in the cross-sectional area and height of the convoluted seminiferous tubules in the tBHQ-treated groups compared to the T-2-treated group (p < 0.05), indicating tBHQ's efficacy in alleviating testicular damage. Additionally, tBHQ treatment significantly inhibited T-2-induced apoptosis of testicular tissue cells, as evidenced by the results showing reduced apoptotic cell counts and downregulation of the BAX/BCL2 ratio and caspase-3 expression (p < 0.05). tBHQ significantly increased the concentrations of the antioxidant factors SOD, CAT, TAC, and GSH-PX. Furthermore, tBHQ attenuated the inflammatory response induced by T-2 exposure, as indicated by the decreased mRNA expression of the proinflammatory cytokines Tnf, Il1, and Il10 in testicular tissue (p < 0.05). Additionally, tBHQ treatment alleviated the decline in serum testosterone induced by the T-2 and promoted testosterone synthesis gene expression, including for the genes 17β-HSD and Cyp11a1, in rat testes (p < 0.05). These findings underscore tBHQ's role as a therapeutic agent combatting T-2-induced reproductive toxicity, highlighting its antioxidative, anti-apoptotic, and anti-inflammatory properties. Further elucidation of tBHQ's mechanisms of action may offer novel strategies for preventing and treating reproductive disorders induced by environmental toxins.

Keywords: T-2; apoptosis; inflammation; oxidative stress; tert-butylhydroquinone; testis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
tBHQ alleviates T-2 induced testicular injury. (A–D) are at 200× magnification, with a scale bar of 100 μm, while (E–H) are at 400× magnification, with a scale bar of 50 μm. (A,E) represent the control group, (B,F) represent the T-2 group, (C,G) represent the tBHQ+T-2 group, and (D,H) represent the M group. Testicular tissue sections stained with hematoxylin and eosin (HE) were observed under a light microscope. In the control group, germ cells were orderly arranged in various layers, with thick walls of the convoluted seminiferous tubules and abundant spermatozoa in the tubular lumens at the locations indicated by the red-boxed triangles in (A,E). Conversely, in the experimental groups, germ cells were loosely arranged and disorganized, with thinning walls of the convoluted seminiferous tubules and reduced numbers of mature spermatozoa in the tubular lumens at the locations indicated by the red-boxed triangles in (B–D,F,H). Under high magnification, observations of the T2 group revealed basal membrane disruptions in the walls of the convoluted seminiferous tubules (indicated by the black arrow in (B)), with numerous germ cells being detached from the tubular lumens (indicated by the black arrow in (F)), and the black-lined area in (H) defines the cross-sectional area of the convoluted seminiferous tubules. The area within the blue lines defines the luminal area. The average length of the four green double-headed arrows represents the height of the germinal epithelium. (I) Cross-sectional area of the convoluted seminiferous tubules. (J) Height of the convoluted seminiferous tubules. n = 8. * represents a significance difference, with p < 0.05. ** represents a significance difference (p < 0.01).
Figure 2
Figure 2
tBHQ inhibits T-2-induced apoptosis of testicular cells. (A) TUNEL staining; (B) semi-quantitative analysis of apoptotic cell ratio using TUNEL staining fluorescence; (C) mRNA expression levels of apoptotic factors Bax, Bcl2, and Caspase-3; (D–F) protein expression levels of Bax and Bcl2, represented by grayscale values; (E–G) protein expression levels of Caspase-3, represented by grayscale values. n = 10. * represents a significant difference, with p < 0.05. ** represents a significant difference, with p < 0.01.
Figure 3
Figure 3
tBHQ alleviates the inflammatory response induced by T-2. (A) mRNA expression levels of inflammatory factors; (B,D) protein expression levels and phosphorylation of JAK, represented by grayscale values; (C,E) protein expression levels and phosphorylation of STAT3, represented by grayscale values. n = 8. * represents a significant difference, with p < 0.05. ** represents a significant difference, with p < 0.01.
Figure 4
Figure 4
tBHQ Attenuates T-2-induced decrease in serum testosterone levels and promotes expression of testosterone synthesis genes. (A) Concentrations of Gnrh, FSH, and LH in rat serum. (B) Concentration of testosterone in serum. (C) mRNA expression levels of steroid hormone synthesis genes. n = 10. * represents a significant difference, with p < 0.05. ** represents a significant difference for p < 0.01.
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