Sugar coated liposomal flavonoid: A unique formulation in combating carbontetrachloride induced hepatic oxidative damage

Abstract

Rats were administered a single dose of plant origin phenolic antioxidant Quercetin (QC) in free, liposome encapsulated and galactosylated liposome encapsulated forms 2 h prior to hepatotoxic dose of carbontetrachloride (CCl₄, 40% v/v in olive oil, 1 ml/kg b.wt). Among those three different forms of QC tested, only galactosylated liposomal QC provided significant protection against CCl₄ induced hepatic oxidative damage. After 24 h of injection (S.C.) hepatic cells of rats were found susceptible to CCl₄ induced oxidative damage and it was monitored by the increased amount of conjugated diene in hepatic membrane. The two-fold increase in conjugated diene by the induction of CCl₄ was decreased upto normal level by galactosylated liposomal QC pre-treatment.

Carbontetrachloride induced membrane damage in hepatic cells and it was judged by the blood serum pathological and liver tissue histopathological examination. Membrane damage by the induction of CCl₄ was further evaluated by the decreased level of plasma membrane (PM) bound enzyme Na⁺/K⁺ ATPase activity and it was increased only by the pre-treatment of galactosylated liposomal QC.

Carbontetrachloride induced a substantial decrease both in enzymatic and molecular endogenous antioxidant levels in hepatic cells.

The depression in antioxidant system in hepatic cells was completely prevented by a single dose of galactosylated lipsosomal QC prior to CCl₄ treatment.

Liver uptake of QC was estimated after 2 h of the flavonoid injection (8.9 μmol/kg body weight) (free or liposomal forms) and 85% of the injected QC was found in liver in the case of galactosylated liposomal QC. Whereas only 25% of the injected dose was detected in liver when an identical amount of free QC was injected.

Carbontetrachloride also induced an alteration in membrane fluidity and it was evaluated by a decrease in membrane micro-viscosity. Free QC pre-treatment resulted in no protection against CCl₄ induced increase in hepatic membrane fluidity, whereas galactosylated liposomal QC exerted a significant protection against the increase. Results of this study revealed that QC in galactosylated liposome could exert a significant protection against CCl₄ induced hepatocellular injury.

Keywords: :

• Quercetin
• galactosylated liposomes
• carbon tetrachloride
• hepatotoxicity
• oxidative stress
• membrane fluidity