title: Mitigating role of baicalein on lysosomal enzymes and xenobiotic metabolizing enzyme status during lung carcinogenesis of Swiss albino mice induced by benzo(a)pyrene.
abstract: The lungs mainly serve as a primary site for xenobiotic metabolism and constitute an important defense mechanism against inhalation of carcinogens. Our current study aimed to evaluate the chemotherapeutic efficacy of baicalein (BE) in Swiss albino mice exposed to tobacco-specific carcinogen benzo(a)pyrene [B(a)P] for its ability to mitigate pulmonary carcinogenesis. Here, we report that altered activities/levels of lysosomal enzymes (cathepsin-D, cathepsin-B, acid phosphatase, β-D-galactosidase, β-D-glucuronidase, and β-D-N-acetyl glucosaminidase), phase I biotransformation enzymes (cytochrome P450, cytochrome b5, NADPH-cytochrome P450 reductase, and NADH-cytochrome b5 reductase), and phase II enzymes (glutathione S-transferase, UDP-glucuronyl transferase, and DT-diaphorase) were observed in the B(a)P-induced mice. Treatment with BE significantly restored back the activities/levels of lysosomal enzymes, phase I and phase II biotransformation enzymes. Moreover, assessment of lysosomal abnormalities by transmission electron microscopic examination revealed that BE treatment effectively counteract B(a)P-induced oxidative damages. Protein expression levels studied by immunohistochemistry, immunofluorescence, and immunoblot analysis of CYP1A1 revealed that BE treatment effectively negate B(a)P-induced upregulated expression of CYP1A1. Further analysis of scanning electron microscopic studies in lung was carried out to substantiate the anticarcinogenic effect of BE. The overall data suggest that BE treatment significantly inhibits lysosomal and microsomal dysfunction, thus revealing its potent anticarcinogenic effect.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India.
authors.forename: Chandrashekar
authors.initials: C
authors.lastname: Naveenkumar
authors.forename: Subramanian
authors.initials: S
authors.lastname: Raghunandakumar
authors.forename: Selvamani
authors.initials: S
authors.lastname: Asokkumar
authors.forename: John
authors.initials: J
authors.lastname: Binuclara
authors.forename: Balan
authors.initials: B
authors.lastname: Rajan
authors.forename: Thandavamoorthy
authors.initials: T
authors.lastname: Premkumar
authors.forename: Thiruvengadam
authors.initials: T
authors.lastname: Devaki
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics / Q000633:toxicity*; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D044950:Flavanones / Q000008:administration & dosage / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008175:Lung Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D051379:Mice; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D015262:Xenobiotics / Q000493:pharmacokinetics*
chemical_list: D016588:Anticarcinogenic Agents; D044950:Flavanones; D015262:Xenobiotics; D001564:Benzo(a)pyrene; C006680:baicalein; D019363:Cytochrome P-450 CYP1A1
keywords: baicalein; benzo(a)pyrene; chemoprevention; lysosomal enzymes; xenobiotic enzymes