Association Between Serum CK-18 Levels and the Degree of Liver Damage in Fructose-Induced Metabolic Syndrome.

BACKGROUND:The pathogenesis of nonalcoholic fatty liver disease as a component of metabolic syndrome (MetS) involves the activation of apoptosis in steatotic hepatocytes. Caspase-generated fragments such as cytokeratin-18 (CK-18) in patients with various hepatic impairments are investigated as markers for diagnosis and assessment of disease severity. The goal of the study was to capture early biomarkers of apoptosis and elucidate their role in assessing the presence and extent of hepatic damage in a MetS model. MATERIALS AND METHODS:We used male Wistar rats, divided into two groups (n = 7): control and high-fructose drinking (HFD) (35% fructose corn syrup for 16 weeks). Metabolic disorders and liver damage were studied by histochemistry (hematoxylin and eosin), immunohistochemical, immunological, and biochemical testing. RESULTS:Our results showed significant increase in liver and serum levels of CK-18 and pro/antiapoptotic Bax/Bcl2 ratio, and decreased levels of HMGB1 (marker of necrosis) in the HFD group when compared with the control. All HFD rats developed obesity, hyperglycemia, hepatomegaly, microvesicular steatosis, an imbalance in hepatic antioxidative defense by measuring malondialdehyde and sulfhydryl groups (SH) with no inflammation and fibrosis, elevated serum levels of triglycerides, tumor necrosis factor alpha (TNF-α), and C-reactive protein without changes in serum aminotransferase levels relative to the control group. As a result of the applied regression analysis, we have determined that the variables TNF-α (0.92) and SH (0.659) have a strong complex effect on hepatic CK-18 levels with predicted value of the model R = 0.9. CONCLUSION:The elevated CK-18 serum levels in the HFD group and their association with the histological changes in the liver and biochemical indicators demonstrate the key role of apoptosis in the pathogenesis of HFD-induced liver damage and the reliability of CK-18 as a biomarker for noninvasive assessment of liver damages in MetS.

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