How does zinc chelation affect liver sphingolipid metabolism in an Alzheimer's-like model?

Abstract

BACKGROUND: The present study aimed to evaluate the impact of Cyclo-Z, a combination of Cyclo (His-Pro) plus zinc, on hepatic sphingolipid (SL) metabolism and antioxidant properties in a rat model of Alzheimer's disease (AD). METHODS: Alzheimer's disease rat model created via intracerebroventricular (i.c.v.) amyloid beta-42 oligomer (AβO) injection into the lateral ventricles. Cyclo-Z administration was performed with daily gavage for 3 weeks after the AβO injection. Ceramide, ceramide kinase (CERK), sphingosine 1 phosphate (S1P), glutathione (GSH), total oxidant capacity (TOS), 4-hydroxynonenal (HNE) and caspase-3 levels were measured with Elisa kit in liver tissue. RESULTS: S1P, CERK and GSH levels increased and ceramide, TOS, 4 HNE, and caspase-3 levels decreased in the liver tissues of AD group. Cyclo-Z treatment decreased S1P, CERK, ceramide and caspase-3 levels but increased TOS and 4-HNE levels in the liver tissues of AD group. CONCLUSION: These results showed that SL metabolism was modulated to generate an anti-apoptotic defense system in liver tissue of AD rats.