Protective effects of baicalein on tert-butyl hydroperoxide-induced hepatic toxicity in rat hepatocytes.

Institute of Medicine, Medical College, Chung Shan Medical University, Taichung, 402, Taiwan.
Journal of Biomedical Science (Impact Factor: 2.46). 02/2005; 12(2):389-97. DOI: 10.1007/s11373-005-1572-8
Source: PubMed

ABSTRACT Baicalein (BAL), a main flavonoid constituent of Scutellaria radix, was studied for its inhibitory effects on tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity and oxidative damage in primary cultures of rat hepatocytes. In a preliminary study, baicalein revealed effective antioxidant properties in a test of its capacity to quench the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH). Further investigations showed that baicalein, at the concentrations of 1, 5, and 10 microM, decreased the leakage of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) and the formation of malondialdehyde (MDA) induced by 30 min of pretreatment with t-BHP (1.5 mM) in primary cultures of rat hepatocytes. Baicalein also attenuated t-BHP-induced mitochondrial depolarization as determined by a retention test of rhodamine 123 and DNA repair synthesis as evidenced by unscheduled DNA synthesis (UDS). In addition, baicalein decreased the 8-hydroxy-2'-deoxyguanosine (8-OH-dG) content which acts as a DNA damage marker. The sum of the results suggests that the protective effect of baicalein against the cytotoxicity and genotoxicity of hepatocytes induced by t-BHP is due to its ability to quench free radicals.

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    ABSTRACT: Our current study aimed to evaluate the chemotherapeutic efficacy of baicalein (BE) in Swiss 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 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 Swiss albino mice.
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