Naringenin and Vanillin Mitigate Cadmium-Induced Pancreatic Injury in Rats via Inhibition of JNK and p38 MAPK Pathways

Background: Cadmium can induce pancreatic injury via oxidative stress, inflammation and apoptosis. Naringenin (NGN) and vanillin (VLN) exert antioxidant, anti-inflammatory, and antiapoptotic effects. Objective: The likely ameliorative effects of NGN, VLN and their combination were studied in rats exposed to cadmium-induced pancreatic injury. Materials and Methods: Rats received NGN (50 mg/kg/day, p.o.), VLN (100 mg/ kg/day, p.o.), or NGN + VLN for 7 days and one injection of CdCl₂ (2 mg/kg, i.p.) on the 6^th day. Results: Cadmium significantly lowered serum amylase and insulin levels. Cadmium also caused significant increments of malondialdehyde, tumor necrosis factor-α, interleukin-1β, nuclear factor-κB p65, Bax/Bcl-2 ratio and phosphorylated c-Jun N-terminal kinase (p-JNK) and p38 mitogen-activated protein kinases (MAPKs) and significant decrements of reduced glutathione and catalase in the pancreas of rats received CdCl₂. Additionally, CdCl₂ caused marked histopathological necrosis and significantly increased caspase-3 expression in pancreatic tissue. The cadmium-induced biochemical, histopathological and immunohistochemical changes were significantly ameliorated by NGN, VLN and NGN + VLN. However, NGN + VLN caused more significant ameliorative effects than did NGN and VLN alone. Conclusion: NGN, VLN and NGN + VLN afforded significant protection of pancreas in rats exposed to cadmium insult through modulation of JNK and p38 MAPK pathways and inhibition of oxidative stress, inflammation and apoptosis.