MILK WHEY PROTEINS MODULATE ENDOTOXEMIA-INDUCED HEPATOTOXICITY IN RATS

Abstract

Objective: The therapeutic effects of whey protein isolate (WPI), alpha-lactalbumin (a-LA) and beta-lactoglobulin (β-LG) against endotoxemia-induced hepatotoxicity were investigated in female rats. Methods : Endotoxemia was induced by intraperitoneal injection of Escherichia coli lipopolysaccharides ( E. coli LPS) on the 1 st day (4 mg/kg) and the 8 th day (2 mg/kg) in two weeks-experiment during which two dose levels of WPI, a-LA and β-LG (100 and 200 mg/kg) were administered orally to female rats. At the end of the experiment, sera and liver tissues were collected for biochemical assessment of superoxide dismutase (SOD) activity, DNA-fragmentation, total antioxidant capacity (TAC) and tumor necrosis factor-alpha (TNF-α) level as well as immunohistochemical examination of caspase-3 activity and collagen deposition by Masson's trichome staining. Results : Endotoxemia, induced by LPS, significantly decreased hepatic SOD enzymatic antioxidant activity as well as serum total antioxidant capacity (TAC). An elevation in hepatic DNA fragmentation and serum levels of tumor necrosis factor-alpha (TNF-α) was also detected. LPS showed strong activation of caspase-3 in perivascular and parenchymal hepatocytes. Abundant bridging of pericentral collagen fibers in hepatotoxic rats was evident in Masson’s trichrome staining. Oral treatment with WPI, a-LA and β-LG (100 and 200 mg/kg) inhibited the decrease in hepatic SOD activity and abrogated hepatic DNA damage. Serum levels of TNF-α decreased significantly while serum TAC was improved by WPI, a-LA and β-LG treatment in hepatotoxic groups. These results were confirmed by immune histochemical examination of activated caspase-3 and Masson’s trichrome staining of enhanced collagen deposition which were modulated by whey proteins (WPs) after two weeks of treatment. Conclusion: Milk - derived WPI, a-LA and β-LG can be a tool in combating hepatotoxicity induced by invasive endotoxemia.