title: Long Chain Fatty Acid Esters of Quercetin-3-O-glucoside Attenuate H₂O₂-induced Acute Cytotoxicity in Human Lung Fibroblasts and Primary Hepatocytes.
abstract: Cellular oxidative stress causes detrimental effects to macromolecules, such as lipids, nucleic acids and proteins, leading to many pathological conditions. Quercetin-3-O-glucoside (Q3G), a glycosylated derivative of quercetin (Q), is a natural polyphenolic compound known to possess antioxidant activity. The hydrophilic/lipophilic nature of an antioxidant molecule is considered as an important factor governing the accessibility to the active sites of oxidative damages in vivo. Six long chain fatty acid esters of Q3G were evaluated with comparison to Q and Q3G, for their cytoprotective activity under H₂O₂-induced oxidative stress using cell culture model systems through cell viability, lipid peroxidation and fluorescence microscopy studies. Pre-incubation of α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) esters of Q3G exhibited significantly (p ≤ 0.05) greater cell viability in both human lung fibroblast (WI-38) and human primary hepatocytes upon exposure to H₂O₂ insult when compared to the control. Cytoprotection due to oleic acid and linoleic acid esters of Q3G was observed only in human primary hepatocytes. All the derivatives, Q3G and quercetin showed ability to significantly (p ≤ 0.05) lower production of lipid hydroperoxides under induced oxidative stress, compared to the control. However, ALA and DHA esters of Q3G resulted in significantly lower lipid hydroperoxidation than Q and Q3G. Based on fluorescence microscopy study, H₂O₂-induced apoptosis was attenuated by the fatty acid derivatives of Q3G. The fatty acid derivatives of Q3G possess better cytoprotective effect than Q3G against H₂O₂-induced cytotoxicity in vitro and the concentration should be selected to avoid cytotoxicity.
authors.affiliation: Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada. sumudunw@dal.ca.
authors.forename: Sumudu N
authors.initials: SN
authors.lastname: Warnakulasuriya
authors.affiliation: Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada. ziachem_315@yahoo.com.
authors.lastname: Ziaullah
authors.affiliation: Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada. vrupasinghe@dal.ca.|Department of Pathology, Faculty of Medicine, Dalhousie University, Truro, NS B2N 5E3, Canada. vrupasinghe@dal.ca.
authors.forename: H P Vasantha
authors.initials: HP
authors.lastname: Rupasinghe
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D019610:Cytoprotection / Q000187:drug effects*; D004952:Esters / Q000737:chemistry; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004952:Esters; D005227:Fatty Acids; C016527:isoquercitrin; D011794:Quercetin
keywords: apoptosis; cytoprotection; human lung fibroblasts; human primary hepatocytes; lipid oxidation; natural product derivatives; oxidative stress