Mandal Ardhendu K, Das Nirmalendu
Indian Institute of Chemical Biology, Biomembrane Division, 4, Raja S.C. Mullick Road, Kolkata, 700032, India.
J Drug Target. 2005 Jun;13(5):305-15. doi: 10.1080/10611860500230278.
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 micromol/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.
在给予大鼠肝毒性剂量的四氯化碳（CCl4，40% v/v溶于橄榄油，1 ml/kg体重）前2小时，分别以游离形式、脂质体包封形式和半乳糖基化脂质体包封形式给予大鼠单剂量植物源酚类抗氧化剂槲皮素（QC）。在测试的这三种不同形式的QC中，只有半乳糖基化脂质体QC对CCl4诱导的肝脏氧化损伤提供了显著保护。注射（皮下）24小时后，发现大鼠肝细胞易受CCl4诱导的氧化损伤，这通过肝细胞膜中共轭二烯量的增加来监测。通过半乳糖基化脂质体QC预处理，CCl4诱导的共轭二烯增加两倍的情况降低至正常水平。CCl4诱导肝细胞的膜损伤，这通过血清病理学和肝组织组织病理学检查来判断。通过质膜（PM）结合酶Na+/K+ ATP酶活性水平的降低进一步评估CCl4诱导的膜损伤，而仅通过半乳糖基化脂质体QC预处理可使其升高。CCl4导致肝细胞中酶促和分子内源性抗氧化剂水平大幅下降。在CCl4处理前，单剂量的半乳糖基化脂质体QC完全预防了肝细胞抗氧化系统的抑制。在注射黄酮类化合物（8.9微摩尔/千克体重）（游离或脂质体形式）2小时后估计肝脏对QC的摄取，在半乳糖基化脂质体QC的情况下，85%的注射QC在肝脏中被发现。而当注射相同量的游离QC时，肝脏中仅检测到25%的注射剂量。CCl4还诱导了膜流动性的改变，这通过膜微粘度的降低来评估。游离QC预处理对CCl4诱导的肝细胞膜流动性增加没有保护作用，而半乳糖基化脂质体QC对这种增加有显著保护作用。本研究结果表明，半乳糖基化脂质体中的QC对CCl4诱导的肝细胞损伤可发挥显著保护作用。
