20 research outputs found

    Attenuating Oxidative Stress by Paeonol Protected against Acetaminophen-Induced Hepatotoxicity in Mice

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    <div><p>Acetaminophen (APAP) overdose is the most frequent cause of drug-induced acute liver failure. The purpose of this study was to investigate whether paeonol protected against APAP-induced hepatotoxicity. Mice treated with paeonol (25, 50, 100 mg/kg) received 400 mg/kg acetaminophen intraperitoneally (i.p.) and hepatotoxicity was assessed. Pre-treatment with paeonol for 6 and 24 h ameliorated APAP-induced hepatic necrosis and significantly reduced the serum alanine aminotransferase (ALT) and aspartate transaminase (AST) levels in a dose-dependent manner. Post-treatment with 100 mg/kg paeonol ameliorated APAP-induced hepatic necrosis and reduced AST and ALT levels in the serum after APAP administration for 24 h. Western blot revealed that paeonol inhibited APAP-induced phosphorylated JNK protein expression but not p38 and Erk1/2. Moreover, paeonol showed anti-oxidant activities with reducing hepatic MDA contents and increasing hepatic SOD, GSH-PX and GSH levels. Paeonol dose-dependently prevented against H<sub>2</sub>O<sub>2</sub> or APAP-induced LDH releasing and ROS production in primary mouse hepatocytes. In addition, the mRNA levels of pro-inflammatory genes such as TNF-α, MCP-1, IL-1β and IL-6 in the liver were dose-dependently reduced by paeonol pre-treatment. Pre-treatment with paeonol significantly inhibited IKKα/β, IκBα and p65 phosphorylation which contributed to ameliorating APAP-induced hepatic inflammation. Collectively, the present study demonstrates paeonol has a protective ability against APAP-induced hepatotoxicity and might be an effective candidate compound against drug-induced acute liver failure.</p></div

    Post-treatment with paeonol protected against APAP-induced liver injury.

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    <p>Mice were intraperitoneally injected with either 400 mg/kg APAP or an equal volume of PBS. After 30 min, mice were administered with either vehicle (0.5% CMC-Na) or paeonol (25, 50, 100 mg/kg) by gavage. Liver tissue and blood were collected after paeonol treatment for 24 h. (A) Liver sections were stained with H&E. Magnification: 200X. (B) The levels of ALT and AST in the serum were determined by a commercially available kit. Data are shown as means ± S.E.M. *<i>P</i><0.05, **<i>P</i><0.01 v.s. APAP treatment (n = 8).</p

    Paeonol inhibited APAP-induced MAPK pathway activation.

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    <p>The protein levels of total and phosphorylated p38, JNK and Erk1/2 in the liver were determined by western blot. β-actin was used as the endogenous control. The representative data are shown and bands were analyzed by densitometry. Data are shown as means ± S.E.M. *<i>P</i><0.05, **<i>P</i><0.01 v.s. APAP treatment.</p

    Paeonol inhibited APAP-induced hepatic inflammation.

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    <p>Total RNA from liver was isolated and hepatic mRNA levels of pro-inflammatory genes were determined by qPCR. GAPDH was used as the endogenous control. Data are shown as means ± S.E.M. *<i>P</i> <0.05, **<i>P</i><0.01 v.s. APAP treatment (n = 8).</p

    Paeonol reduced APAP-induced hepatic oxidative stress.

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    <p>(A) Mice were administered with either vehicle (0.5% CMC-Na) or paeonol (25, 50, 100 mg/kg) by gavage for three days. At day 3, mice were intraperitoneally injected with either 400 mg/kg APAP or an equal volume of PBS. Liver was collected and hepatic homogenates were used for the determination of MDA, SOD, GSH and GSH-PX levels by using commercial kits. (B) Mice were administered with either vehicle (0.5% CMC-Na) or paeonol (25, 50, 100 mg/kg) by gavage for three days. At day 3, mice were co-treated with either 400 mg/kg APAP and 300 mg/kg NAC by intraperitoneal injection. The levels of ALT and AST in the serum were determined by a commercially available kit. (C) The protein levels of total and phosphorylated JNK in the liver were determined by western blot. β-actin was used as the endogenous control. The representative data are shown and bands were analyzed by densitometry. Data are shown as means ± S.E.M. *<i>P</i><0.05, **<i>P</i><0.01 v.s. APAP treatment (n = 8).</p

    Paeonol prevented against H<sub>2</sub>O<sub>2</sub> or APAP-induced LDH releasing and ROS production in primary mouse hepatocytes.

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    <p>Primary mouse hepatocytes were treated with paeonol (20, 40, 80 μM) in the absence or presence of 5 mM APAP or 250 μM H<sub>2</sub>O<sub>2</sub> for 6 h. (A) LDH leakage percentage were determined by a commercial kit. (B) ROS formation was measured using a fluorescence microplate reader. Data are shown as means ± S.E.M. *<i>P</i><0.05, **<i>P</i><0.01 v.s. APAP treatment.</p

    Paeonol significantly inhibited IKKα/β, IκBα and p65 phosphorylation in APAP-treated liver.

    No full text
    <p>The protein levels of total and phosphorylated IKKα/β, IκBα and p65 in the liver were determined by western blot. β-actin was used as the endogenous control. The representative data are shown and bands were analyzed by densitometry. Data are shown as means ± S.E.M. *<i>P</i><0.05, **<i>P</i><0.01 v.s. APAP treatment.</p

    Pre-treatment with paeonol protected against APAP-induced liver injury.

    No full text
    <p>Mice were administered with either vehicle (0.5% CMC-Na) or paeonol (25, 50, 100 mg/kg) by gavage for three days. At day 3, mice were intraperitoneally (i.p.) injected with either 400 mg/kg APAP or an equal volume of PBS. Liver tissues were collected after APAP administration for 6 h (A) and 24 h (B). Liver sections were stained with H&E. Magnification: 200X. (C) After APAP administration for 6 h, blood was collected and the levels of ALT and AST in the serum were determined by a commercially available kit. Data are shown as means ± S.E.M. *<i>P</i><0.05, **<i>P</i><0.01 v.s. APAP treatment (n = 8).</p

    Intratumoral CD8<sup>+</sup> Cytotoxic Lymphocyte Is a Favorable Prognostic Marker in Node-Negative Breast Cancer

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    <div><p>Background</p><p>The prognostic effect of tumor infiltrating CD8<sup>+</sup> cytotoxic lymphocytes (CTLs) in breast cancer is controversial. We analyzed the association between CD8<sup>+</sup> CTLs and survival of untreated node-negative breast cancer patients.</p><p>Material and Methods</p><p>CD8<sup>+</sup> CTLs infiltrate was evaluated by immunostaining in a cohort of 332 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of CD8<sup>+</sup> CTLs for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate analysis and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 expression and human epidermal growth factor receptor 2 (HER-2) status.</p><p>Results</p><p>285 (85.8%) patients showed strong CD8<sup>+</sup> CTLs infiltrate positive status. Univariate analysis showed that CD8<sup>+</sup> CTLs had statistically significant association with DFS (P = 0.004, hazard ratio [HR] = 0.454, 95% confidence interval [CI] = 0.265–0.777) and OS (P = 0.014, HR = 0.430, 95% CI = 0.220–0.840) in the entire cohort. The significance of CD8<sup>+</sup> CTLs was especially strong in ER negative, HER-2 negative and ER, PR, HER-2 triple-negative breast cancers. In Kaplan-Meier analysis, CD8<sup>+</sup> CTLs had significant effect on prognosis of patients (Log-rank test: P = 0.003 for DFS and P = 0.011 for OS), independent of established clinical factors for DFS (P = 0.002, HR = 0.418, 95% CI = 0.242–0.724) as well as for OS (P = 0.009, HR = 0.401, 95% CI = 0.202–0.797).</p></div
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