The Association Between Thyroid Injury and Apoptosis, and Alterations of Bax, Bcl-2, and Caspase-3 mRNA/Protein Expression Induced by Nickel Sulfate in Wistar Rats

Abstract

To study the toxicity induced by Nickel sulfate (NiSO₄) on thyroid tissue, and investigate the role of apoptosis as the possible mechanism, thirty-two male Wistar rats were randomly divided into control group (normal saline, ip), low dose group (2.5 mg/kg day NiSO₄, ip), middle dose group (5 mg/kg day NiSO₄, ip), high dose group (10 mg/kg day NiSO₄, ip). After 40 consecutive days of treatment, there were obvious pathological changes in the thyroids of high dose group. Free T₄ (FT₄) and thyroid-stimulating hormone (TSH) were significantly lower in the NiSO₄-treated groups than those in the control group (F = 4.992, p = 0.016; F = 4.524, p = 0.012). The mRNA expression of Caspase-3 was significantly higher (F = 10.259, p = 0.014) in all NiSO₄-treated groups, and the mRNA expression of Bcl-2 was significantly lower (F = 9.225, p = 0.018) only in the high dose group. Both control group and the NiSO₄-treated groups showed no changes in the mRNA expression of Bax gene. The ratio of Bcl-2/Bax decreased with the increase in exposure dose of NiSO₄ (F = 13.382, p = 0.015). The mRNA expression of Fas went up in high dose group (F = 66.632, p < 0.001). The Caspase-3, Fas, and the Bax protein expressions measured by immunohistochemistry were consistent with the mRNA expression. The expression of Bcl-2 protein was significantly lower in the test groups than in the control group (F = 3.873, p = 0.025). NiSO₄ as an Endocrine Disrupting Chemical may induce the thyroid injury through apoptosis and lead to hypothyroidism. Also, apoptosis in thyroid tissues was closely related to the alternations of Caspase-3, Bcl-2, and Fas mRNA and protein expression.

Keywords: Apoptosis protein; Nickel sulfate; Thyroid hormone; Thyroid injury; mRNA expression.