Hesperidin protects against cadmium-induced pancreatitis by modulating insulin secretion, redox imbalance and iNOS/NF-κB signaling in rats

Aim: Cadmium is a persistent ubiquitous environmental toxicant that elicits several biological defects on deli-cate body organs. Growing evidence suggests that cadmium (Cd) may perturb signaling pathways to induce oxidative pancreatitis. Thus, we explored whether hesperidin, a flavonone, could mitigate Cd-induced oxidative stress-mediated inflammation and pancreatitis in Wistar rats. Main methods: Forty (40) rats randomly assigned to 5 groups (n = 8) were administered normal saline or hesperidin (Hsp) followed by Cd intoxication for 28 days. Key findings: Cadmium accumulated in the pancreas of rats, and markedly decreased insulin, pancreatic superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and glutathione (GSH) level. Cadmium considerably increased malondialdehyde (MDA), serum lipase and amylase activities. Cadmium induced pancreatic pro-inflammation via over-expression of inducible nitric oxide synthase (iNOS), nuclear factor KB (NF-kappa B), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), along with histopathological alterations. Hesperidin prominently decreased serum amylase and lipase activities, and markedly increased insulin level, pancreatic antioxidant defense mechanism, whereas iNOS, NF-kappa B, IL-6 and TNF-alpha levels significantly decreased. Changes in histology confirmed our biochemical findings. Significance: Our findings suggest that Cd induced pancreatitis via pro-inflammation and oxidative stress; Hsp, thus, protects against Cd-induced pancreatitis via attenuation of oxidative stress and proinflammatory responses in pancreas.