Boron Compounds Mitigate 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Toxicity in Human Peripheral Blood Mononuclear Cells

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) stands as one of the most potent halogenated polycyclic hydrocarbons, known to inflict substantial cytotoxic effects on both animal and human tissues. Its widespread presence and recalcitrance make it an environmental and health concern. Efforts are being intensively channeled to uncover strategies that could mitigate the adverse health outcomes associated with TCDD exposure. In the realm of counteractive agents, boron compounds are emerging as potential candidates. These compounds, which have found applications in a spectrum of industries ranging from agriculture to pharmaceutical and cosmetic manufacturing, are known to modulate several cellular processes and enzymatic pathways. However, the dose-response relationships and protective potentials of commercially prevalent boron compounds, such as boric acid (BA), ulexite (UX), and borax (BX), have not been comprehensively studied. In our detailed investigation, when peripheral blood mononuclear cells (PBMCs) were subjected to TCDD exposure, they manifested significant cellular disruptions. This was evidenced by compromised membrane integrity, a marked reduction in antioxidant defense mechanisms, and a surge in the malondialdehyde (MDA) levels, a recognized marker for oxidative stress. On the genomic front, increased 8-OH-dG levels and chromosomal aberration (CA) frequency suggested that TCDD had the potential to cause DNA damage. Notably, our experiments have revealed that boron compounds could act as protective agents against these disruptions. They exhibited a pronounced ability to diminish the cytotoxic, genotoxic, and oxidative stress outcomes instigated by TCDD. Thus, our findings shed light on the promising role of boron compounds. In specific dosages, they may not only counteract the detrimental effects of TCDD but also serve as potential chemopreventive agents, safeguarding the cellular and genomic integrity of PBMCs.

Keywords: TCDD; boron compounds; cytotoxicity; genotoxicity; oxidative status.

Figure 1

The effect of 48 h treatment with different concentrations of tetrachlorodibenzo-p-dioxin (TCDD) on peripheral blood mononuclear cell (PBMC) viability. Data are presented as mean ± SEM. Significant difference p < 0.001 (***) compared to the negative control group (NC: negative control, SEM: standard error of the mean).

Figure 2

The effect of 48 h treatment with different concentrations of boric acid (BA), borax (BX), or ulexite (UX) (2.5–10 mg/L) (a) and 48 h co-treatment with different concentrations of BA, BX, or UX (2.5–10 mg/L) against tetrachlorodibenzo-p-dioxin (TCDD) (0.1 mg/L) toxicity (b), on peripheral blood mononuclear cell (PBMC) viability. Data are presented as mean ± SEM. Significant difference p < 0.05 (*), p < 0.01 (**), and p < 0.001 (***), compared to the TCDD-only group (NC: negative control, PC: positive control, SEM: standard error of the mean).

Figure 3

The activity of LDH released into the supernatant of peripheral blood mononuclear cell (PBMC) cultures 48 h after treatment with boric acid (BA), borax (BX), or ulexite (UX) (2.5–10 mg/L) (a) and 48 h co-treatment with different concentrations of BA, BX, or UX (2.5–10 mg/L) against tet-rachlorodibenzo-p-dioxin (TCDD) (0.1 mg/L) toxicity (b). Data are presented as mean ± SEM. Significant difference p < 0.001 (***), compared to the TCDD-only group (NC: negative control, PC: positive control, SEM: standard error of the mean).

Figure 4

Sample images of metaphase plates investigated by using the chromosomal aberration test. Image of CA test performed on PBMC cultures treated with (A) TCDD (0.1 mg/L) only, (B) TCDD (0.1 mg/L) + boric acid (10 mg/L), (C) negative control (no treatment). Red arrows show translocations and breaks in (A), and translocation in (B).

Figure 5

Effect of exposure to TCDD (0.1 mg/L) with BA, BX, and UX (10 mg/L) for 24 h on (A)—SOD (U/g tissue), (B)—CAT (U/g tissue), (C)—GSH (mg/g tissue), and (D)—GPx (mg/g tissue) in PBMC cultures. One-way ANOVA and Dunnett tests were used for multiple comparison. Letters (A–C) show statistically significant results compared to each other.

Figure 5

Effect of exposure to TCDD (0.1 mg/L) with BA, BX, and UX (10 mg/L) for 24 h on (A)—SOD (U/g tissue), (B)—CAT (U/g tissue), (C)—GSH (mg/g tissue), and (D)—GPx (mg/g tissue) in PBMC cultures. One-way ANOVA and Dunnett tests were used for multiple comparison. Letters (A–C) show statistically significant results compared to each other.

Figure 5

Effect of exposure to TCDD (0.1 mg/L) with BA, BX, and UX (10 mg/L) for 24 h on (A)—SOD (U/g tissue), (B)—CAT (U/g tissue), (C)—GSH (mg/g tissue), and (D)—GPx (mg/g tissue) in PBMC cultures. One-way ANOVA and Dunnett tests were used for multiple comparison. Letters (A–C) show statistically significant results compared to each other.

Figure 5

Effect of exposure to TCDD (0.1 mg/L) with BA, BX, and UX (10 mg/L) for 24 h on (A)—SOD (U/g tissue), (B)—CAT (U/g tissue), (C)—GSH (mg/g tissue), and (D)—GPx (mg/g tissue) in PBMC cultures. One-way ANOVA and Dunnett tests were used for multiple comparison. Letters (A–C) show statistically significant results compared to each other.

Figure 6

Effect of exposure to TCDD (0.1 mg/L) with BA, BX, and UX (10 mg/L) for 24 h on TNF-α and IL-6 levels in PBMC cultures. Letters (A–C) show statistically significant results compared to control. One-way ANOVA and Dunnett tests were used for multiple comparison. Letters (A–D) show statistically significant results compared to each other.