MAPK/iNOS pathway is involved in swine kidney necrosis caused by cadmium exposure

Highlights: • Cadmium (Cd) exposure may induce necrosis in swine kidney. • Cd exposure may activate p38 and JNK pathways, rather than ERK1/2 in swine kidney. • Cd exposure may activate iNOS pathways in swine kidney by increasing p38 and JNK. • Activation of iNOS pathways might cause programmed necrosis in swine kidney. Cadmium (Cd) pollution in the environment could cause toxic damage to animals and humans. MAPK pathways could regulate their downstream inflammatory factors, and plays a crucial role in necrosis. Since the swine kidney tissue is an important accumulation site of Cd and target organ of its toxic damage, but the damage form of Cd to swine kidney and the role of MAPK pathways in it are still not clear, we selected six week old weaned piglets as the research object, and fed a diet supplemented CdCl₂ (20 mg/kg) to establish the model of liver injury induced by Cd. The expressions and phosphorylation of MAPK pathways (ERK, JNK, p38), expression levels of inflammatory factors (TNF-α, NF-κB, iNOS, COX-2 and PTGE) and necrosis related genes (MLKL, RIPK1, RIPK3 and FADD) and heat shock proteins (HSPs) were detected by RT-PCR and Western blot. H.E. staining was used to determine the damage of kidney caused by Cd exposure. The results showed that Cd exposure could activate p38 and JNK pathway phosphorylation, rather than ERK 1/2, up regulated the expressions of inflammatory factors, finally induced programmed necrosis (increasing the expressions of MLKL, RIPK1, RIPK3 and FADD) in swine kidney. Our study elucidated the mechanism of Cd-damage to swine kidney and the relationship among MAPK pathways, inflammatory factors and programmed necrosis in swine.