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: 2.76). 02/2005; 12(2):389-97. DOI: 10.1007/s11373-005-1572-8
Source: PubMed


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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    • "Liver is the key organ of metabolism and excretion of many substances; hence it is often exposed to variety of xenobiotics and therapeutic agents. Hepatic fibrosis induced by chronic liver injuries as a result of hepatitis viruses, chronic alcohol intake, lipidperoxidative products and various drugs could end by cirrhosis [1]. Chronic liver diseases are usually associated with inflammatory reaction that is considered a key contributor of hepatocellular damage with a resultant progression to liver fibrosis and may be to hepatocellular carcinoma [2]. "
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    ABSTRACT: This work was undertaken to establish a new experimental model of hepatic fibrosis by gamma irradiation and CCl 4 and to study the hepatoprotective effect of Reishi Mushroom (RM) against hepatic fibrosis induced in that model. Our results revealed that oral co-administration of 110 mg/kg RM by gavage to fibrotic rats offered an obvious hepatic protection as assured by the significant decrement in ALT and AST, HP content, MDA and NO levels with elevation of the antioxi-dant enzymes activities. The levels of TGF-β, TNF-α, HO-1 and type-1 collagen and their m-RNA expression were markedly declined as compared with those of fibrotic rats. Microscopical examination revealed that the exposure of rats to radiation aggravated the effect of CCl4 causing extensive collagen deposition and marked pseudolobulation of the hepatic parenchyma indicative of bridging fibrosis. While, oral co-administration of RM obviously improved the state of steatosis and apparently suppressed hepatic fibrogenesis.
    Journal of Biosciences and Medicines 11/2015; 3(10):24-38. DOI:10.4236/jbm.2015.310004
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    • "In the present study, the optimum concentration of t-BHP to exhibit hepatotoxicity measured by MDA formation and ALT leakage was 1.5 mM. This concentration is in line with previous studies where incubation of hepatocytes with 2 mM t-BHP for 30 min caused approximately 73% of LDH leakage and 5 nmol/10 6 cells MDA formation (Rush et al. 1985; Hwang et al. 2005). Another study also reported 75% cell dead on incubating hepatocytes for 1 h with 0.5 mM t-BHP (Masaki et al. 1989a). "
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    ABSTRACT: Context: Curcuma comosa Roxb. (Zingiberaceae) has traditionally been used as an anti-inflammatory agent in liver, and recent study has shown its hepatoprotective effect against CCl4-induced liver injury in vivo. Objective: This study further assesses the protective effect of C. comosa extracts and its isolated compounds against tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in isolated primary rat hepatocytes. Materials and methods: Isolated primary hepatocytes were pretreated with either ethanol (5-50 μg/ml) or hexane extract (1-50 μg/ml), or two diarylheptanoids (4-35 μM): compound D-91 [1-(4-hydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol] and compound D-92 [(3S)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol], from C. comosa for 2 h prior to exposure to 1.5 mM t-BHP for 15 and 30 min. Their hepatoprotective activities were then determined. Results: t-BHP markedly caused the formation of MDA and ALT leakage from the hepatocytes. Pretreatment with the C. comosa ethanol extract showed greater protective effect than the hexane extract, and the effect was concentration related. Treating the hepatocytes with compound D-92 provided greater protective effect than compound D-91. IC50 values of compounds D-91, D-92, and silymarin for the protection of ALT leakage at 30 min were 32.7 ± 1.1, 9.8 ± 0.7, and 160 ± 8 μM, respectively. Further investigation showed that compound D-92 was more effective in maintaining the intracellular glutathione content in the t-BHP treated group, whereas the reduction in antioxidant enzymes, glutathione peroxidase and glutathione-S-transferase activities, were not improved. Discussion and conclusion: Results suggest that diarylheptanoids are the active principles that provide protection against t-BHP-induced injury. Their ability to maintain intracellular glutathione content is the main mechanisms underlying the protective action.
    Pharmaceutical Biology 10/2015; DOI:10.3109/13880209.2015.1088550 · 1.24 Impact Factor
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    • "Recent studies have shown that baicalein has beneficial effects in the liver. Baicalein attenuates tert-butyl hydroperoxide-induced hepatic toxicity in rat hepatocytes (Hwang et al., 2005). Baicalein inhibits hepatocellular carcinoma cells invasion and metastasis by reducing cell motility and migration (Chen et al., 2013). "
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    ABSTRACT: Liver dysfunction has been known to occur frequently in cases of sepsis. Baicalein, the main active ingredient of the Scutellaria root, exerts anti-inflammatory and anti-apoptotic properties in endotoxic shock. However, the role of baicalein in polymicrobial sepsis-induced liver injury and its regulatory mechanisms remain unclear. In this study, we aimed to investigate the protective effects of baicalein on polymicrobial sepsis-induced liver injury and to explore the possible mechanisms. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Mice were treated with baicalein (100mg/kg, i.p) at 1h, 6h and 12h following CLP. Baicalein significantly improved the survival of septic mice. Treatment with baicalein ameliorated the CLP-induced liver injury, as indicated by the lower serum aminotransferase levels and the fewer histopathologic abnormalities. Baicalein reduced the neutrophil infiltration and the hepatic inflammatory cytokine expression and release. It also decreased the hepatic and the serum high-mobility group box 1 and macrophage migration inhibitory factor levels in septic mice. Moreover, baicalein significantly inhibited the mitogen-activated protein kinases (MAPKs) activation and suppressed the transcriptional activity of nuclear factor-kappa B (NF-κB). In conclusion, these results suggest that baicalein treatment could protect against the sepsis-induced liver injury, and improve the survival of mice with polymicrobial sepsis. The mechanism of the protective action of baicalein seems to involve its ability to reduce inflammatory response, inhibit hepatic apoptosis, and to suppress MAPKs and NF-κB activation. Copyright © 2014. Published by Elsevier B.V.
    European Journal of Pharmacology 12/2014; 748. DOI:10.1016/j.ejphar.2014.12.014 · 2.53 Impact Factor
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