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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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Liver immunohistochemical analysis of 4-HNE.Typical images were selected from each experimental group (original magnification: 200×). (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). (G) IOD values of 4-HNE staining 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-g006: Liver immunohistochemical analysis of 4-HNE.Typical images were selected from each experimental group (original magnification: 200×). (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). (G) IOD values of 4-HNE staining 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: Clivorine (210 mg/kg) increased the MDA and GSH levels in the liver (P<0.001), but quercetin (90 mg/kg) reversed such increase (P<0.01) (Figs. 5A and B). Quercetin (60 mg/kg) also decreased clivorine-induced increase in the GSH level (P<0.05). Liver immunostaining of 4-HNE, which is a marker for LPO, was weak in the control and quercetin (90 mg/kg)-treated mice (Figs. 6A and F). The 4-HNE staining cells increased in clivorine-treated mice (Fig. 6B). Quercetin (60 and 90 mg/kg) reduced clivorine-increased 4-HNE staining cells (Figs. 6D and E). The statistical result in Fig. 6G demonstrated that clivorine enhanced the immunohistochemical staining of 4-HNE, contrary to the evident quercetin (60 and 90 mg/kg)-induced reduction in clivorine-increased 4-HNE staining (P<0.01, P<0.001).


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)

Liver immunohistochemical analysis of 4-HNE.Typical images were selected from each experimental group (original magnification: 200×). (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). (G) IOD values of 4-HNE staining 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

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

pone-0098970-g006: Liver immunohistochemical analysis of 4-HNE.Typical images were selected from each experimental group (original magnification: 200×). (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). (G) IOD values of 4-HNE staining 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: Clivorine (210 mg/kg) increased the MDA and GSH levels in the liver (P<0.001), but quercetin (90 mg/kg) reversed such increase (P<0.01) (Figs. 5A and B). Quercetin (60 mg/kg) also decreased clivorine-induced increase in the GSH level (P<0.05). Liver immunostaining of 4-HNE, which is a marker for LPO, was weak in the control and quercetin (90 mg/kg)-treated mice (Figs. 6A and F). The 4-HNE staining cells increased in clivorine-treated mice (Fig. 6B). Quercetin (60 and 90 mg/kg) reduced clivorine-increased 4-HNE staining cells (Figs. 6D and E). The statistical result in Fig. 6G demonstrated that clivorine enhanced the immunohistochemical staining of 4-HNE, contrary to the evident quercetin (60 and 90 mg/kg)-induced reduction in clivorine-increased 4-HNE staining (P<0.01, P<0.001).

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