Vesicular flavonoid in combating diethylnitrosamine induced hepatocarcinoma in rat model.
Reactive oxygen species (O2(*-), OH(-), H2O2) are known to play an important role in tumor initiation in hepatocarcinoma. Hepatocarcinoma was developed in the Swiss Albino rats by administration three doses of diethylnitrosamine (DEN) (200 mg/kg b. wt.) (i.p.) at 15 days interval. Quercetin (QC), herbal polyphenolic compound, is a potent anticancer drug. Clinical trials are difficult for its hydrophobic nature. To overcome this problem, our study was aimed to formulate soluble liver specific, galactosylated liposomal QC and to investigate its efficacy against hepatocarcinoma in rat model. Galactosylated liposomal QC was formulated and the suspension was introduced intravenously to rats (8.98 microM/kg) once in a week for 16 weeks. Hepatocarcinoma in rat model and its pathological improvement were evaluated histopathologically, histochemically and electron microscopically. Severe oxidative damage was noticed in the whole liver and its microsomal fraction of DEN treated rats. Huge numbers of hyperplastic nodules (HNs) with pre-neoplastic lesions appeared in rat liver by DEN administration. Galactosylated liposomal QC injections prevented DEN mediated development of hepatocarcinoma and oxidative damage in rat liver. Quercetin in liver specific galactosylated liposomal drug delivery system may be recommended as a potent therapeutic formulation against DEN-induced hepatocarcinoma.
Mandal
Ardhendu K
AK
Biomembrane Division, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata-700032, India.
Das
Sanchari
S
Mitra
Maitreyi
M
Chakrabarti
Rohini N
RN
Chatterjee
Malay
M
Das
Nirmalendu
N
D000477:Alkylating Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D004052:Diethylnitrosamine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004337:Drug Carriers; D004339:Drug Compounding; D005690:Galactose / Q000737:chemistry; D005979:Glutathione Peroxidase / Q000378:metabolism; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes; D008113:Liver Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008862:Microsomes, Liver / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats
D000477:Alkylating Agents; D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002273:Carcinogens; D004337:Drug Carriers; D007364:Intercalating Agents; D008081:Liposomes; D004052:Diethylnitrosamine; D011794:Quercetin; D002374:Catalase; D005979:Glutathione Peroxidase; D005690:Galactose