Oxidative stress, apoptosis and inflammatory responses involved in copper-induced pulmonary toxicity in mice

At present, there are few studies focused on the relationship between copper (Cu) and oxidative stress, apoptosis, or inflammatory responses in animal and human lungs. This study was conducted to explore the effects of Cu on pulmonary oxidative stress, apoptosis and inflammatory responses in mice orally administered with 0 mg/kg (control), 10 mg/kg, 20 mg/kg, and 40 mg/kg of CuSO₄ for 42 days. The results showed that CuSO₄ increased ROS production, and MDA, 8-OHdG and NO contents as well as iNOS activities and mRNA expression levels. Meanwhile, CuSO₄ reduced the activities and mRNA expression levels of antioxidant enzymes (GSH-Px, CAT, and SOD) and GSH contents, and ASA and AHR abilities. Also, CuSO₄ induced apoptosis, which was accompanied by decreasing Bcl-2, Bcl-xL mRNA expression levels and protein expression levels, and increasing Bax, Bak, cleaved-caspase-3, cleaved-caspase-9 mRNA, and protein expression levels, and Bax/Bcl-2 ratio. Concurrently, CuSO₄ caused inflammation by increasing MPO activities and activating the NF-κB signalling pathway, and down-regulating the mRNA and protein expression levels of anti-inflammatory cytokines (IL-2, IL-4, IL-10). In conclusion, the abovementioned findings demonstrated that over 10 mg/kg CuSO₄ can cause oxidative stress, apoptosis, and inflammatory responses, which contribute to pulmonary lesions and dysfunction in mice.