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Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling.

Lin BR, Yu CJ, Chen WC, Lee HS, Chang HM, Lee YC, Chien CT, Chen CF - J. Biomed. Sci. (2009)

Bottom Line: GT pretreatment attenuated ROS production, mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, plasma ALT and cytokines levels, biliary acute phase proteins secretion and hepatic pathology by the enhancement of anti-apoptotic mechanisms.In conclusion, D-GalN induced ALI via hypoxia/hypoperfusion-enhanced mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, contributing to oxidative stress and inflammation in the liver.GT can counteract the D-GalN-induced ALI via the attenuation of apoptotic and proinflammatory signaling by the upregulation of anti-apoptotic mechanism.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Taiwan University College of Medicine, Taipei, Taiwan. brucelin@ntuh.gov.tw

ABSTRACT
Oxidative stress and inflammation contributed to the propagation of acute liver injury (ALI). The present study was undertaken to determine whether D-galactosamine (D-GalN) induces ALI via the mitochondrial apoptosis- and proinflammatory cytokine-signaling pathways, and possible mechanism(s) by which green tea (GT) extract modulates the apoptotic and proinflammatory signaling in rat. D-GalN induced hepatic hypoxia/hypoperfusion and triggered reactive oxygen species (ROS) production from affected hepatocytes, infiltrated leukocytes, and activated Kupffer cells. D-GalN evoked cytosolic Bax and mitochondrial cytochrome C translocation and activated proinflammatory nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) translocation, contributing to the increase of intercellular adhesion molecule-1 expression, terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL)-positive hepatocytes, multiple plasma cytokines and chemokines release, and alanine aminotransferase (ALT) activity. An altered biliary secretion profile of several acute phase proteins directly indicates oxidative stress affecting intracellular trafficking in the hepatocyte. GT pretreatment attenuated ROS production, mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, plasma ALT and cytokines levels, biliary acute phase proteins secretion and hepatic pathology by the enhancement of anti-apoptotic mechanisms. In conclusion, D-GalN induced ALI via hypoxia/hypoperfusion-enhanced mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, contributing to oxidative stress and inflammation in the liver. GT can counteract the D-GalN-induced ALI via the attenuation of apoptotic and proinflammatory signaling by the upregulation of anti-apoptotic mechanism.

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Leukocytic infiltration (indicated by green arrows, B-C), lipogenic accumulation (indicated by stars *, B, H, K), nitroblue tetrazolium (NBT) deposits (blue precipitate indicated by green arrows, E), hepatic Kupffer cell (ED1) stain (brown stain, D-F), 4-hydroxy-2-nonenal (4-HNE) stain (brown color, H), and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) stain were used to demonstrate de novo production of oxidative stress in the D-GalN treated liver. Oxidative stress indicated by NBT (green arrows) appeared in the Kupffer cells (identified by ED1 brown color) and hepatocytes of rat livers subjected to 24 hr of D-GalN treatment (E), but less evident in the control liver (D) and the liver with low dose of GT pretreatment (F). 4-HNE stain for oxidized protein concomitantly occurred in the D-GalN treated hepatocyte with lipogenic accumulation (H), but not appeared in the control (G) or GT pretreated livers (I). TUNEL stain for apoptotic cell death was absent in the control liver (J) and GT treated liver (L), but appeared in the liver after 24 hr of D-GalN treatment (K). A-C, hematoxylin and eosin stain, × 400; D-F, NBT+ED1 counterstain, × 400; G-I, 4-HNE stain, × 600;J-L, TUNEL stain, × 400.
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Figure 6: Leukocytic infiltration (indicated by green arrows, B-C), lipogenic accumulation (indicated by stars *, B, H, K), nitroblue tetrazolium (NBT) deposits (blue precipitate indicated by green arrows, E), hepatic Kupffer cell (ED1) stain (brown stain, D-F), 4-hydroxy-2-nonenal (4-HNE) stain (brown color, H), and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) stain were used to demonstrate de novo production of oxidative stress in the D-GalN treated liver. Oxidative stress indicated by NBT (green arrows) appeared in the Kupffer cells (identified by ED1 brown color) and hepatocytes of rat livers subjected to 24 hr of D-GalN treatment (E), but less evident in the control liver (D) and the liver with low dose of GT pretreatment (F). 4-HNE stain for oxidized protein concomitantly occurred in the D-GalN treated hepatocyte with lipogenic accumulation (H), but not appeared in the control (G) or GT pretreated livers (I). TUNEL stain for apoptotic cell death was absent in the control liver (J) and GT treated liver (L), but appeared in the liver after 24 hr of D-GalN treatment (K). A-C, hematoxylin and eosin stain, × 400; D-F, NBT+ED1 counterstain, × 400; G-I, 4-HNE stain, × 600;J-L, TUNEL stain, × 400.

Mentions: Significant lipid accumulation was detected in helatocytes 24–72 hrs after D-GalN treatment (Figure 6). GT pretreatment reduced the appearance of fatty liver (Figure 6C).


Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling.

Lin BR, Yu CJ, Chen WC, Lee HS, Chang HM, Lee YC, Chien CT, Chen CF - J. Biomed. Sci. (2009)

Leukocytic infiltration (indicated by green arrows, B-C), lipogenic accumulation (indicated by stars *, B, H, K), nitroblue tetrazolium (NBT) deposits (blue precipitate indicated by green arrows, E), hepatic Kupffer cell (ED1) stain (brown stain, D-F), 4-hydroxy-2-nonenal (4-HNE) stain (brown color, H), and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) stain were used to demonstrate de novo production of oxidative stress in the D-GalN treated liver. Oxidative stress indicated by NBT (green arrows) appeared in the Kupffer cells (identified by ED1 brown color) and hepatocytes of rat livers subjected to 24 hr of D-GalN treatment (E), but less evident in the control liver (D) and the liver with low dose of GT pretreatment (F). 4-HNE stain for oxidized protein concomitantly occurred in the D-GalN treated hepatocyte with lipogenic accumulation (H), but not appeared in the control (G) or GT pretreated livers (I). TUNEL stain for apoptotic cell death was absent in the control liver (J) and GT treated liver (L), but appeared in the liver after 24 hr of D-GalN treatment (K). A-C, hematoxylin and eosin stain, × 400; D-F, NBT+ED1 counterstain, × 400; G-I, 4-HNE stain, × 600;J-L, TUNEL stain, × 400.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2667169&req=5

Figure 6: Leukocytic infiltration (indicated by green arrows, B-C), lipogenic accumulation (indicated by stars *, B, H, K), nitroblue tetrazolium (NBT) deposits (blue precipitate indicated by green arrows, E), hepatic Kupffer cell (ED1) stain (brown stain, D-F), 4-hydroxy-2-nonenal (4-HNE) stain (brown color, H), and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) stain were used to demonstrate de novo production of oxidative stress in the D-GalN treated liver. Oxidative stress indicated by NBT (green arrows) appeared in the Kupffer cells (identified by ED1 brown color) and hepatocytes of rat livers subjected to 24 hr of D-GalN treatment (E), but less evident in the control liver (D) and the liver with low dose of GT pretreatment (F). 4-HNE stain for oxidized protein concomitantly occurred in the D-GalN treated hepatocyte with lipogenic accumulation (H), but not appeared in the control (G) or GT pretreated livers (I). TUNEL stain for apoptotic cell death was absent in the control liver (J) and GT treated liver (L), but appeared in the liver after 24 hr of D-GalN treatment (K). A-C, hematoxylin and eosin stain, × 400; D-F, NBT+ED1 counterstain, × 400; G-I, 4-HNE stain, × 600;J-L, TUNEL stain, × 400.
Mentions: Significant lipid accumulation was detected in helatocytes 24–72 hrs after D-GalN treatment (Figure 6). GT pretreatment reduced the appearance of fatty liver (Figure 6C).

Bottom Line: GT pretreatment attenuated ROS production, mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, plasma ALT and cytokines levels, biliary acute phase proteins secretion and hepatic pathology by the enhancement of anti-apoptotic mechanisms.In conclusion, D-GalN induced ALI via hypoxia/hypoperfusion-enhanced mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, contributing to oxidative stress and inflammation in the liver.GT can counteract the D-GalN-induced ALI via the attenuation of apoptotic and proinflammatory signaling by the upregulation of anti-apoptotic mechanism.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Taiwan University College of Medicine, Taipei, Taiwan. brucelin@ntuh.gov.tw

ABSTRACT
Oxidative stress and inflammation contributed to the propagation of acute liver injury (ALI). The present study was undertaken to determine whether D-galactosamine (D-GalN) induces ALI via the mitochondrial apoptosis- and proinflammatory cytokine-signaling pathways, and possible mechanism(s) by which green tea (GT) extract modulates the apoptotic and proinflammatory signaling in rat. D-GalN induced hepatic hypoxia/hypoperfusion and triggered reactive oxygen species (ROS) production from affected hepatocytes, infiltrated leukocytes, and activated Kupffer cells. D-GalN evoked cytosolic Bax and mitochondrial cytochrome C translocation and activated proinflammatory nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) translocation, contributing to the increase of intercellular adhesion molecule-1 expression, terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL)-positive hepatocytes, multiple plasma cytokines and chemokines release, and alanine aminotransferase (ALT) activity. An altered biliary secretion profile of several acute phase proteins directly indicates oxidative stress affecting intracellular trafficking in the hepatocyte. GT pretreatment attenuated ROS production, mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, plasma ALT and cytokines levels, biliary acute phase proteins secretion and hepatic pathology by the enhancement of anti-apoptotic mechanisms. In conclusion, D-GalN induced ALI via hypoxia/hypoperfusion-enhanced mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, contributing to oxidative stress and inflammation in the liver. GT can counteract the D-GalN-induced ALI via the attenuation of apoptotic and proinflammatory signaling by the upregulation of anti-apoptotic mechanism.

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Related in: MedlinePlus