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: 2.74). 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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    • "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 · 2.68 Impact Factor
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    • "The hepatocellular carcinoma cell lines HepG2 and SK-Hep1 were obtained from the American Tissue Culture Collection (ATCC, USA) and grown to confluence in Dulbecco's minimum essential medium (Gibco, USA) supplemented with 10% fetal bovine serum (Gibco, USA), 2 mM Glutamine, 1% non essential amino acids (NEAA) and a 1% antibiotic mixture (50 mg/mL of penicillin, 50 mg/ mL of streptomycin, and 10 mg/mL of neomycin/mL) at 37 C in a humidified atmosphere of 5% CO 2 . The primary rat hepatocytes were isolated from Wistar rats as previously described [14]. The isolated hepatocytes (viability > 90%) were prepared by liver perfusion with collagenase IV (Sigma) and separated by density centrifugation in Percoll solution (GE Healthcare Bio-Sciences AB). "
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    ABSTRACT: Previous research indicates that cantharidin, norcantharidin and their analogues exhibit anticancer activity due to their inhibition of cancer cell lines such as HL60, HT29 and L1210. The anticancer activities of cantharidin, norcantharidin and their analogues involve the suppression of serine/threonine protein phosphatases (PPs) activity. However, cantharidin is not suitable for cancer therapy because of its high cytotoxicity in vitro (IC(50) = 21 microM in primary cultured rat hepatocytes). In this study, synthetic cantharidin analogues with a structure of aminothiazole compounds 3-9 and a structure of anhydride compounds 10-12 were screened for anticancer activities and cytotoxic effects on human hepatocellular carcinoma cell (HCC) lines HepG2, Sk-Hep1, and primary cultured rat hepatocytes. Experimental results indicated that compounds 3-9 did not perform as expected with regard to anticancer activity and exhibited lower cytotoxicity. Compound 10 promoted apoptosis in HepG2 (IC(50) = 62 microM) and SK-Hep1(IC(50) = 151 microM) cell lines. Compounds 11 and 12 had anticancer potential similar to that of compound 10. After treatment with compounds 3-12, primary cultured rat hepatocytes exhibited no cytotoxicity (IC(50) > 200 microM). By investigating the structure-activity relationship (SAR) of these analogues as a whole, this study suggests that the anhydride ether oxygen such as in cantharidin, norcantharidin and compounds 10-12 may be correlated with HCC survival suppression. The results further suggest that the elimination of bridging ether oxygen on the ring, such as in compounds 10-12, can decrease cytotoxicity.
    European Journal of Medicinal Chemistry 09/2010; 45(9):3981-5. DOI:10.1016/j.ejmech.2010.05.053 · 3.43 Impact Factor
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    ABSTRACT: In the present study, we examined the protective mechanism of baicalein (BE) and its glycoside, baicalin (BI), on hydrogen-peroxide (H(2)O(2))-induced cell death in rat glioma C6 cells. Results of the MTT assay, LDH release assay, and morphological observation showed that H(2)O(2) addition reduced the viability of C6 cells, and this was prevented by the addition of BE but not BI. Incubation of C6 cells with BE significantly decreased the intracellular peroxide level induced by H(2)O(2) according to flow cytometric analysis using DCHF-DA as a fluorescent substrate. Suppression of H(2)O(2)-induced apoptotic events including DNA ladders, hypodiploid cells, and activation of caspases 3, 8, and, 9 by BE but not BI was identified in C6 cells. The cytotoxicity and phosphorylation of ERK proteins induced by H(2)O(2) were blocked by the ERK inhibitor PD98059. Catalase addition prevented H(2)O(2)-induced ROS production, ERKs protein phosphorylation, and cell death, and BE dose-dependently inhibited H(2)O(2)-induced ERK protein phosphorylation in C6 cells. These data suggest that ROS-scavenging activity is involved in BE prevention of H(2)O(2)-induced cell death via blocking ERKs activation. Additionally, BE but not BI induced heat shock protein 32 (HSP32; HO-1) protein expression in both time- and dose-dependent manners, but not heme oxygenase 2 (HO-2), heat shock protein 70 (HSP70), or heat shock protein 90 (HSP90) protein expression. In the absence of H(2)O(2), BE induces ERKs protein phosphorylation, and HO-1 protein expression induced by BE was blocked by the addition of cycloheximide, actinomycin D, and the ERK inhibitor PD98059. The addition of the HO inhibitor ZnPP inhibited the protective effect of BE against H(2)O(2)-induced cytotoxicity in C6 cells according to the MTT assay and apoptotic morphology under microscopic observation, accompanied by blocking the ROS-scavenging activity of BE in C6 cells. However, BE treatment was unable to protect C6 cells from C2-ceramide-induced cell death. These data indicate that BE possesses abilities to inhibit ROS-mediated cytotoxic effects through modulation of ERKs activation and induction of HO-1 protein expression. The role of HO-1 in ROS-scavenging activity of BE is proposed.
    Toxicology and Applied Pharmacology 11/2006; 216(2):263-73. DOI:10.1016/j.taap.2006.05.008 · 3.63 Impact Factor
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