Decreased thioredoxin reductase 3 expression promotes nickel-induced damage to cardiac tissue via activating oxidative stress-induced apoptosis and inflammation.

Abstract

Thioredoxin reductase 3 (Txnrd3) plays a crucial role in antioxidant and anti-cancer activities, and sperm maturation. The damage of heavy metals, including Nickel (Ni), is the most prominent harm in social development, and hampering Txnrd3 might exacerbate Ni-induced cardiac damage. In this study, a total of 160 8-week-old C57BL/N male mice with 25-30 g weight of Txnrd3+/+ wild-type and Txnrd3-/- homozygote-type were randomly divided into eight groups. The mice in the control and Ni groups were gavaged with distilled water and a freshly prepared 10mg/kg NiCl2 solution. Melatonin (Mel) groups were administered at a concentration of 2mg/kg for 21 days at the mice's 0.1ml/10g body weight. Ni exposure up-regulated the messenger RNA (mRNA) levels of mitochondrial apoptosis (caspase-3, caspase-9, cytochrome c, p53, and BAX), autophagy (LC3, ATG 1, ATG 7, and Beclin-1), and inflammation (TNF-α, COX 2, IL-1β, IL-2, IL-6, and IL-7)-related markers, but down-regulated the mRNA levels of BCL-2, p62 and mTOR (p < .05). Ni exposure decreased the expression of BCL-2 and p62 protein but increased the expression levels of caspase-3, caspase-9, cytochrome c, p53, BAX, ATG 7, Beclin-1, TNF-α, COX 2, IL-1β and IL-2 protein (p < .05). Ni increased the contents of glutathione disulfide (GSSG) and malondialdehyde (MDA) and decreased the activities of catalase (CAT) and total superoxide dismutase (T-SOD) (p < .05). Decreased Txnrd3 expression significantly exacerbated changes compared to the Ni exposure (p < .05). Mel significantly attenuated these changes, but the effect decreased when Txnrd3 was inhibited (p < .05). In conclusion, decreased Txnrd3 expression promoted Ni-induced mitochondrial apoptosis and inflammation via oxidative stress and aggravated heart damage in mice. Decreased Txnrd3 expression significantly reduced the protective effect of Mel to Ni exposure.