Comparing the Influence of High Doses of Different Zinc Salts on Oxidative Stress and Energy Depletion in IPEC-J2 Cells

The current study aimed to investigate the influence of four supplemental zinc salts (chelated: Zn glycine; non-chelated: Zn sulfate, Zn citrate, Zn gluconate) among different zinc concentrations (30-300 μM) on cell proliferation, oxidative stress, and energy depletion in intestinal porcine jejunum epithelial cells (IPEC-J2). Different zinc salts affected cell viability in a time- and dose-dependent manner, which was mainly dependent on the uptake of intracellular Zn²⁺. Intracellular Zn²⁺ of Zn sulfate has taken up almost twice as high as Zn glycine when cells were loaded with 100-200 μM zinc. After loading cells with 300 μM zinc, Zn glycine and Zn sulfate had a similar trend in accumulation of Zn²⁺. When the intracellular Zn²⁺ overloads, cells will gradually be damaged and subsequently die bearing biochemical features of necrosis or late Apoptosis. Meanwhile, obviously, increased levels of intracellular ROS, mitochondrial ROS, MDA, and NO and decreased levels of GSH were observed. Excessive intracellular Zn²⁺ significantly decreased mitochondria membrane potential accompanied by an obvious loss of ATP and NAD⁺ levels. Overall, exposure to high doses of zinc salts caused cell damage, which was mainly dependent on the uptake of Zn²⁺. Zinc overload induced oxidative stress and energy depletion in IPEC-J2 cells, and the cell damage with non-chelated zinc addition was more serious than Zn glycine.