Enhanced pancreatic toxicity induced by cadmium and a high-fat diet: attenuation by naringin through the modulation of oxidative stress, apoptosis, and inflammatory signaling.

Increasing exposure to cadmium, an environmental pollutant from industrial and agricultural activities, and changing lifestyles and a tendency to consume high-fat foods, has raised serious concerns about metabolic health. We designed this study to investigate the combined effects of cadmium and a high-fat diet on pancreatic function. We also evaluated the protective potential of naringin, a natural flavonoid with antioxidant and anti-inflammatory properties. In our 12-week experimental study, we exposed 64 female NMRI mice to a high-fat diet (58.8 % calories from fat) and different levels of cadmium (0.5 and 5 ppm in drinking water). We administered naringin at doses of 50 and 100 mg/kg/day via gavage. Our results showed that a high-fat diet and cadmium combination significantly disrupted glucose homeostasis, characterized by increased fasting blood sugar and decreased glucose tolerance. We also observed a decrease in plasma insulin levels and impaired beta-cell function, which we associated with increased oxidative stress, pancreatic inflammation, impaired mitochondrial function, and the induction of cell apoptosis. Notably, the pancreas of the high-fat diet group accumulated more cadmium than the pancreas of the low-fat diet group. Administration of naringin improved glucose and insulin status, reduced oxidative stress and inflammation, protected mitochondrial function, and inhibited apoptosis of pancreatic cells. As the first comprehensive study on the exacerbated effects of cadmium and a high-fat diet, our research provides evidence of naringin's protective effects by examining multiple levels, from metabolic parameters to molecular mechanisms. These findings highlight the potential importance of naringin as a protective agent against metabolic disorders caused by exposure to environmental pollutants and unhealthy diets, but also provide a solid foundation for future clinical applications in the prevention and treatment of these disorders.