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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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Hepatocyte apoptosis was evaluated via TUNEL staining assay.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 apoptotic hepatocytes. (G) The apoptotic hepatocytes were counted manually in at least three random fields every section. Data are expressed as means ± SEM (n = 6). *P<0.05 compared with the control; #P<0.05 compared with clivorine.
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pone-0098970-g003: Hepatocyte apoptosis was evaluated via TUNEL staining assay.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 apoptotic hepatocytes. (G) The apoptotic hepatocytes were counted manually in at least three random fields every section. Data are expressed as means ± SEM (n = 6). *P<0.05 compared with the control; #P<0.05 compared with clivorine.

Mentions: From the TUNEL assay, no apoptotic cells were found in the liver of the control mice (Fig. 3A). After clivorine administration (210 mg/kg), the liver demonstrated an increased amount of scattered TUNEL-positive apoptotic hepatocytes (Fig. 3B). Administration of various doses of quercetin reduced the TUNEL-positive apoptotic cells enhanced by clivorine (Figs. 3C to E). No apoptotic cells were found in the livers of quercetin (90 mg/kg)-treated mice (Fig. 3F). Apoptotic cell count showed that clivorine (210 mg/kg) obviously increased the number of apoptotic cells (P<0.05), while quercetin (40 and 90 mg/kg) decreased AP-increased apoptotic cell number (P<0.05) (Fig. 3G). Furthermore, Western-blot results (Fig. 4) showed that clivorine decreased the expression of pro-caspase-3 and increased the expression of cleaved caspase-3, which indicates that clivorine can induce the cleaved activation of caspase-3. Quercetin (60, 90 mg/kg) reversed the decreased expression of pro-caspase-3 and the increased expression of cleaved caspase-3 induced by clivorine. The inhibition of quercetin on the cleaved activation of caspase-3 induced by clivorine further evidences that quercetin can inhibit clivorine-induced liver apoptosis.


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)

Hepatocyte apoptosis was evaluated via TUNEL staining assay.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 apoptotic hepatocytes. (G) The apoptotic hepatocytes were counted manually in at least three random fields every section. Data are expressed as means ± SEM (n = 6). *P<0.05 compared with the control; #P<0.05 compared with clivorine.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0098970-g003: Hepatocyte apoptosis was evaluated via TUNEL staining assay.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 apoptotic hepatocytes. (G) The apoptotic hepatocytes were counted manually in at least three random fields every section. Data are expressed as means ± SEM (n = 6). *P<0.05 compared with the control; #P<0.05 compared with clivorine.
Mentions: From the TUNEL assay, no apoptotic cells were found in the liver of the control mice (Fig. 3A). After clivorine administration (210 mg/kg), the liver demonstrated an increased amount of scattered TUNEL-positive apoptotic hepatocytes (Fig. 3B). Administration of various doses of quercetin reduced the TUNEL-positive apoptotic cells enhanced by clivorine (Figs. 3C to E). No apoptotic cells were found in the livers of quercetin (90 mg/kg)-treated mice (Fig. 3F). Apoptotic cell count showed that clivorine (210 mg/kg) obviously increased the number of apoptotic cells (P<0.05), while quercetin (40 and 90 mg/kg) decreased AP-increased apoptotic cell number (P<0.05) (Fig. 3G). Furthermore, Western-blot results (Fig. 4) showed that clivorine decreased the expression of pro-caspase-3 and increased the expression of cleaved caspase-3, which indicates that clivorine can induce the cleaved activation of caspase-3. Quercetin (60, 90 mg/kg) reversed the decreased expression of pro-caspase-3 and the increased expression of cleaved caspase-3 induced by clivorine. The inhibition of quercetin on the cleaved activation of caspase-3 induced by clivorine further evidences that quercetin can inhibit clivorine-induced liver apoptosis.

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