Nickel-smelting fumes induce mitochondrial damage and apoptosis, accompanied by decreases in viability, in NIH/3T3 cells.

Nickel (Ni) is widely present in the occupational environment and causes various adverse effects on the human body. Apoptosis induced by Ni may be a key mechanism underlying its toxic effect. In the present study, we investigated the effect of Ni-smelting fumes on cell viability, mitochondrial damage, and apoptosis-related proteins in NIH/3T3 cells. The effects of Ni-smelting fumes at concentrations of 0, 25, 50, and 100 μg/mL were tested. Treatment with Ni-smelting fumes for 24 h and 48 h significantly decreased cell viability and lactate dehydrogenase activity in a dose- and time-dependent manner compared with the blank control group. Exposure to Ni-smelting fumes increased mitochondrial permeability transition pore opening in a dose-dependent manner and decreased mitochondrial membrane potential and the activity of the mitochondrial respiratory chain complexes I, II, and IV. The fumes significantly downregulated Bcl-2, procaspase-9, and procaspase-3 and upregulated Bax, caspase-9, and caspase-3 (P < 0.05). Ni-smelting fumes caused significant cytotoxicity, oxidative stress, mitochondrial damage, and apoptosis through the intrinsic pathway in mammalian cells. The present paper provides hypotheses and experimental support for these hypotheses that Ni-smelting fumes cause cytotoxicity through the mechanism of inducing mitochondrial damage and apoptosis in NIH/3T3 cells.