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Baicalein Abrogates Reactive Oxygen Species ( ROS )‐mediated Mitochondrial Dysfunction during Experimental Pulmonary Carcinogenesis In Vivo
Author(s) -
Naveenkumar Chandrashekar,
Raghunandhakumar Subramanian,
Asokkumar Selvamani,
Devaki Thiruvengadam
Publication year - 2013
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12025
Subject(s) - glutathione , baicalein , reactive oxygen species , glutathione peroxidase , lipid peroxidation , superoxide dismutase , biochemistry , microbiology and biotechnology , glutathione reductase , chemistry , pharmacology , oxidative stress , biology , enzyme
Our current study aimed to evaluate the chemotherapeutic efficacy of baicalein (BE) in S wiss albino mice, which is exposed to benzo(a)pyrene [B(a)P] for its ability to alleviate mitochondrial dysfunction and systolic failure. Here, we report that oral administration of B(a)P (50 mg/kg body weight)‐induced pulmonary genotoxicities in mice was assessed in terms of elevation in reactive oxygen species (ROS) generation and DNA damage in lung mitochondria. MDA‐DNA adducts were formed in immunohistochemical analysis, which confirmed nuclear DNA damage. mRNA expression levels studied by RT‐PCR analysis of voltage‐dependent anion channel (VDAC) and adenine nucleotide translocase (ANT) were found to be significantly decreased and showed a marked increase in membrane permeability transition pore (MPTP) opening. Accompanied by up‐regulated Bcl‐ xL and down‐regulated Bid, Bim and Cyt‐c proteins studied by immunoblot were observed in B(a)P‐induced lung cancer–bearing animals. Administration of BE (12 mg/kg body weight) significantly reversed all the above deleterious changes. Moreover, assessment of mitochondrial enzyme system revealed that BE treatment effectively counteracts B(a)P‐induced down‐regulated levels/activities of isocitrate dehydrogenase, α‐ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase, cytochrome‐C‐oxidase and ATP levels. Restoration of mitochondria from oxidative damage was further confirmed by transmission electron microscopic examination. Further analysis of lipid peroxidation, superoxide dismutase, catalase, glutathione peroxidase, glutathione‐S‐transferase, glutathione reductase, reduced glutathione, vitamin E and vitamin C in lung mitochondria was carried out to substantiate the antioxidant effect of BE. The overall data conclude that chemotherapeutic efficacy of BE might have strong mitochondria protective and restoration capacity in sub‐cellular level against lung carcinogenesis in S wiss albino mice.