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KMID : 0043320180410030265
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Archives of Pharmacal Research
2018 Volume.41 No. 3 p.265 ~ p.275
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Galangin, a dietary flavonol inhibits tumor initiation during experimental pulmonary tumorigenesis by modulating xenobiotic enzymes and antioxidant status
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Devadoss Dinesh
Ramar Manikandan
Chinnasamy Arulvasu
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Abstract
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The aim of present study was to elucidate anti-initiating efficacy of galangin against benzo(a)pyrene (B(a)P)-induced lung carcinogenesis in male Swiss albino mice. Therefore, the activities of xenobiotic metabolic enzymes such as phase I and II were examined in lung as well as liver tissues (to compare the effects between target and non-target organs). Besides, the activities/levels of tissue marker enzymes, antioxidants, lipid peroxidation (LPO), cytochrome P450 1A1 (CYP1A1) expressions and histological observation of lungs were also analyzed. B(a)P (50 mg/kg body weight) was administered to male Swiss albino mice (20?25 g) to experimentally induce lung cancer. B(a)P-induced animals showed increased activity of phase I (Cytochrome P450, Cytochrome b5, NADPH Cytochrome P450 redcutase and NADH Cytochrome b5 reductase) drug metabolic enzymes, LPO levels, tissue marker enzymes and decreased activity of phase II metabolic enzymes (glutathione-S-transferase, DT-diaphorase and UDP-glucuronyl transferase) as well as antioxidant levels. Histological examination of lungs revealed severe alveolar and bronchiolar damages in B(a)P-induced mice. Immunohistochemical and western blot analysis of CYP1A1 increased significantly in lung tissues of B(a)P-induced animals. Treatment with galangin (20 mg/kg body weight) efficiently counteracted all the above anomalies and restored cellular homeostasis. Our results demonstrate that galangin can modify xenobiotic enzymes in murine model of pulmonary tumorigenesis.
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KEYWORD
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Galangin, Benzo(a)pyrene, Lung cancer, Xenobiotic metabolic enzymes, CYP1A1 and antioxidants
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