Novel long chain fatty acid derivatives of quercetin-3-O-glucoside reduce cytotoxicity induced by cigarette smoke toxicants in human fetal lung fibroblasts

Abstract

Smoking has become a global health concern due to its association with many disease conditions, such as chronic obstructive pulmonary disease (COPD), cardiovascular diseases (CVD) and cancer. Flavonoids are plant polyphenolic compounds, studied extensively for their antioxidant, anti-inflammatory, and anti-carcinogenic properties. Quercetin-3-O-glucoside (Q3G) is a flavonoid which is widely found in plants. Six novel long chain fatty acid [stearic acid, oleic acid, linoleic acid, α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] derivatives of Q3G were evaluated for their potential in protecting human lung fibroblasts against cytotoxicity induced by selected cigarette smoke toxicants: 4-(methylnitrosoamino)-1-(3-pyridinyl)-1-butanone (NNK), benzo-α-pyrene (BaP), nicotine and chromium (Cr[VI]). Nicotine and Cr[VI] induced toxicity in fibroblasts and reduced the percentage of viable cells, while BaP and NNK did not affect cell viability. The fatty acid derivatives of Q3G provided protection against nicotine- and Cr[VI]-induced cell death and membrane lipid peroxidation. Based on the evaluation of inflammatory markers of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2), the fatty acid derivatives of Q3G were found to be effective in lowering the inflammatory response. Overall, these novel fatty acid esters of Q3G warrant further investigation as potential cytoprotective agents.

Keywords: 4-(methylnitrosoamino)-1-(3-pyridinyl)-1-butanone; Benzo-α-pyrene; COX-2; Cell viability; Cigarette smoke; Cytotoxicity; Docosahexaenoic acid; Eicosapentaenoic acid; Human lung fibroblasts; Linoleic acid; Lipid peroxidation; Nicotine and chromium; Oleic acid; PGE(2); Quercetin; Stearic acid; α-linolenic acid.