Copper Induces Spleen Damage Through Modulation of Oxidative Stress, Apoptosis, DNA Damage, and Inflammation

Abstract

Copper (Cu) is an essential micronutrient for both humans and animals; however, excessive intake of Cu can be immunotoxic. There are limited studies on spleen toxicity induced by Cu. This study was conducted to investigate the effects of Cu on spleen oxidative stress, apoptosis, and inflammatory responses in mice orally administered with 0 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg of CuSO₄ for 42 days. As discovered in this work, copper sulfate (CuSO₄) reduced the activities of antioxidant enzymes (SOD, CAT, and GSH-Px), decreased GSH contents, and increased MDA contents. Meanwhile, CuSO₄ induced apoptosis by increasing TUNEL-positive cells in the spleen. Also, CuSO₄ increased the expression of γ-H2AX, which is the marker of DNA damage. Concurrently, CuSO₄ caused inflammation by increasing the mRNA levels of interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). In conclusion, the abovementioned findings demonstrate that over 10 mg/kg CuSO₄ can cause oxidative stress, apoptosis, DNA damage, and inflammatory responses, which contribute to spleen dysfunction in mice.

Keywords: Apoptosis; CuSO4; DNA damage; Inflammatory; Spleen.