High Normal dietary casein attenuates bisphenol A-induced multiorgan toxicity in rats: Preservation of renal integrity, glucose homeostasis, and immune surveillance via modulation of oxidative stress, inflammation, and apoptosis.

Bisphenol A (BPA) causes multiorgan toxicity via oxidative stress, inflammation, and apoptosis, and the effect of nutritionally relevant elevation of casein intake is unknown. To evaluate whether a nutritionally relevant elevation of dietary casein (18% vs. 14%) attenuates BPA-induced multiorgan toxicity in rats, male Wistar rats were divided into four groups (n = 8/group) and treated for 35 days: control (14% casein), casein 18% alone, BPA (50 mg/kg/day +14% casein), and BPA + 18% casein. We measured oxidative and inflammatory markers, renal function, metabolic parameters, hematological parameters, histopathology and immunohistochemistry in kidney, spleen, and pancreas. BPA significantly increased malondialdehyde, interleukin-6, tumor necrosis factor-alpha, creatinine, kidney injury molecule-1, insulin resistance, white blood cells, neutrophils, and monocytes, and decreased reduced glutathione, glutathione S-transferase, superoxide dismutase, catalase, interleukin-4, serum soluble CD4 and CD8 protein levels, hemoglobin, red blood cells, platelets, and lymphocytes. BPA also caused renal tubular necrosis, splenic degeneration, pancreatic fibrosis, and upregulated caspase-3 and inducible nitric oxide synthase. Co-administration of 18% casein partially attenuated these effects, reducing malondialdehyde by 35-40%, creatinine by 40%, and insulin resistance by 53%, and restoring antioxidant enzymes and glucose tolerance. However, several parameters remained significantly different from controls. Nutritionally relevant elevation of casein (18%) provides significant partial protection against BPA-induced toxicity, supporting dietary protein modulation as a supportive strategy.