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Quercetin prevents pyrrolizidine alkaloid clivorine-induced liver injury in mice by elevating body defense capacity.

Ji L, Ma Y, Wang Z, Cai Z, Pang C, Wang Z - PLoS ONE (2014)

Bottom Line: Results also showed that quercetin reduced the increase in liver glutathione and lipid peroxidative product malondialdehyde induced by clivorine.Quercetin reduced the enhanced liver immunohistochemical staining for 4-hydroxynonenal induced by clivorine.Some of the alterations were confirmed by real-time PCR.

View Article: PubMed Central - PubMed

Affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines and Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Shanghai R&D Centre for Standardization of Chinese Medicines, Shanghai, China.

ABSTRACT
Quercetin is a plant-derived flavonoid that is widely distributed in nature. The present study is designed to analyze the underlying mechanism in the protection of quercetin against pyrrolizidine alkaloid clivorine-induced acute liver injury in vivo. Serum transaminases, total bilirubin analysis, and liver histological evaluation demonstrated the protection of quercetin against clivorine-induced liver injury. Terminal dUTP nick end-labeling assay demonstrated that quercetin reduced the increased amount of liver apoptotic cells induced by clivorine. Western-blot analysis of caspase-3 showed that quercetin inhibited the cleaved activation of caspase-3 induced by clivorine. Results also showed that quercetin reduced the increase in liver glutathione and lipid peroxidative product malondialdehyde induced by clivorine. Quercetin reduced the enhanced liver immunohistochemical staining for 4-hydroxynonenal induced by clivorine. Results of the Mouse Stress and Toxicity PathwayFinder RT2 Profiler PCR Array demonstrated that the expression of genes related with oxidative or metabolic stress and heat shock was obviously altered after quercetin treatment. Some of the alterations were confirmed by real-time PCR. Our results demonstrated that quercetin prevents clivorine-induced acute liver injury in vivo by inhibiting apoptotic cell death and ameliorating oxidative stress injury. This protection may be caused by the elevation of the body defense capacity induced by quercetin.

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Histological observation of the protection of quercetin against clivorine-induced liver injury.After treatment, livers were removed, fixed, sectioned (5 µm), and processed for hematoxylin and eosin staining. Typical images were selected from each experimental group (original magnification: 100×). (A) Vehicle control, (B) clivorine (210 mg/kg), (C) clivorine (210 mg/kg) + quercetin (40 mg/kg), (D) clivorine (210 mg/kg) + quercetin (60 mg/kg), (E) clivorine (210 mg/kg) + quercetin (90 mg/kg), and (F) quercetin (90 mg/kg). Arrows indicate the intrahepatic hemorrhage.
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pone-0098970-g002: Histological observation of the protection of quercetin against clivorine-induced liver injury.After treatment, livers were removed, fixed, sectioned (5 µm), and processed for hematoxylin and eosin staining. Typical images were selected from each experimental group (original magnification: 100×). (A) Vehicle control, (B) clivorine (210 mg/kg), (C) clivorine (210 mg/kg) + quercetin (40 mg/kg), (D) clivorine (210 mg/kg) + quercetin (60 mg/kg), (E) clivorine (210 mg/kg) + quercetin (90 mg/kg), and (F) quercetin (90 mg/kg). Arrows indicate the intrahepatic hemorrhage.

Mentions: Clivorine (210 mg/kg) obviously increased serum ALT and AST activity (P<0.01, P<0.001) (Fig. 1A), while quercetin (40, 60, and 90 mg/kg) reduced the clivorine-induced increase in these parameters (P<0.05, P<0.01, P<0.001). Clivorine increased serum TB level (P<0.001), but quercetin inhibited such increase (P<0.01) (Fig. 1B). Additionally, clivorine-treated mice showed severe liver damage, indicating intrahepatic hemorrhage and destruction of liver structure (Fig. 2B). Quercetin can reverse such liver injury in a dose-dependent manner (Figs. 2C to E). A liver histological picture of quercetin (90 mg/kg)-treated mice is shown in Fig. 2F, and no remarkable difference was found compared with control.


Quercetin prevents pyrrolizidine alkaloid clivorine-induced liver injury in mice by elevating body defense capacity.

Ji L, Ma Y, Wang Z, Cai Z, Pang C, Wang Z - PLoS ONE (2014)

Histological observation of the protection of quercetin against clivorine-induced liver injury.After treatment, livers were removed, fixed, sectioned (5 µm), and processed for hematoxylin and eosin staining. Typical images were selected from each experimental group (original magnification: 100×). (A) Vehicle control, (B) clivorine (210 mg/kg), (C) clivorine (210 mg/kg) + quercetin (40 mg/kg), (D) clivorine (210 mg/kg) + quercetin (60 mg/kg), (E) clivorine (210 mg/kg) + quercetin (90 mg/kg), and (F) quercetin (90 mg/kg). Arrows indicate the intrahepatic hemorrhage.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048295&req=5

pone-0098970-g002: Histological observation of the protection of quercetin against clivorine-induced liver injury.After treatment, livers were removed, fixed, sectioned (5 µm), and processed for hematoxylin and eosin staining. Typical images were selected from each experimental group (original magnification: 100×). (A) Vehicle control, (B) clivorine (210 mg/kg), (C) clivorine (210 mg/kg) + quercetin (40 mg/kg), (D) clivorine (210 mg/kg) + quercetin (60 mg/kg), (E) clivorine (210 mg/kg) + quercetin (90 mg/kg), and (F) quercetin (90 mg/kg). Arrows indicate the intrahepatic hemorrhage.
Mentions: Clivorine (210 mg/kg) obviously increased serum ALT and AST activity (P<0.01, P<0.001) (Fig. 1A), while quercetin (40, 60, and 90 mg/kg) reduced the clivorine-induced increase in these parameters (P<0.05, P<0.01, P<0.001). Clivorine increased serum TB level (P<0.001), but quercetin inhibited such increase (P<0.01) (Fig. 1B). Additionally, clivorine-treated mice showed severe liver damage, indicating intrahepatic hemorrhage and destruction of liver structure (Fig. 2B). Quercetin can reverse such liver injury in a dose-dependent manner (Figs. 2C to E). A liver histological picture of quercetin (90 mg/kg)-treated mice is shown in Fig. 2F, and no remarkable difference was found compared with control.

Bottom Line: Results also showed that quercetin reduced the increase in liver glutathione and lipid peroxidative product malondialdehyde induced by clivorine.Quercetin reduced the enhanced liver immunohistochemical staining for 4-hydroxynonenal induced by clivorine.Some of the alterations were confirmed by real-time PCR.

View Article: PubMed Central - PubMed

Affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines and Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Shanghai R&D Centre for Standardization of Chinese Medicines, Shanghai, China.

ABSTRACT
Quercetin is a plant-derived flavonoid that is widely distributed in nature. The present study is designed to analyze the underlying mechanism in the protection of quercetin against pyrrolizidine alkaloid clivorine-induced acute liver injury in vivo. Serum transaminases, total bilirubin analysis, and liver histological evaluation demonstrated the protection of quercetin against clivorine-induced liver injury. Terminal dUTP nick end-labeling assay demonstrated that quercetin reduced the increased amount of liver apoptotic cells induced by clivorine. Western-blot analysis of caspase-3 showed that quercetin inhibited the cleaved activation of caspase-3 induced by clivorine. Results also showed that quercetin reduced the increase in liver glutathione and lipid peroxidative product malondialdehyde induced by clivorine. Quercetin reduced the enhanced liver immunohistochemical staining for 4-hydroxynonenal induced by clivorine. Results of the Mouse Stress and Toxicity PathwayFinder RT2 Profiler PCR Array demonstrated that the expression of genes related with oxidative or metabolic stress and heat shock was obviously altered after quercetin treatment. Some of the alterations were confirmed by real-time PCR. Our results demonstrated that quercetin prevents clivorine-induced acute liver injury in vivo by inhibiting apoptotic cell death and ameliorating oxidative stress injury. This protection may be caused by the elevation of the body defense capacity induced by quercetin.

Show MeSH
Related in: MedlinePlus