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Catechin suppresses an array of signalling molecules and modulates alcohol-induced endotoxin mediated liver injury in a rat model.

Bharrhan S, Koul A, Chopra K, Rishi P - PLoS ONE (2011)

Bottom Line: Additionally, nitrite levels and lactate dehydrogenase activities were also significantly elevated on chronic alcohol consumption.Alcohol exposure also increased the number of micronucleated cells indicating that alcohol abuse may again be associated with the nuclear changes.Moreover, a remarkable decrease in the percentage of micronucleated cells was observed with catechin supplementation indicating an apparent protection against alcohol-induced toxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Basic Medical Sciences Block, Panjab University, Chandigarh, India.

ABSTRACT
Induction of nuclear factor kappa B (NF-κB)-mediated gene expression has been implicated in the pathogenesis of alcoholic liver disease through enhanced production of reactive oxygen species and pro-inflammatory mediators. The present study was carried out to investigate the role of catechin as a chain breaking inhibitor against experimental alcoholic liver injury. Rats were administered 35% v/v ethanol orally at a dose of 10 g/Kg/day for two weeks, followed by 14 g/Kg/day for 10 weeks. Catechin (50 mg/Kg) was co-supplemented after 4 weeks of alcohol treatment till the end of the dosing period. Following chronic alcohol exposure, rats developed endotoxemia and severe pathological changes in the liver such as pronounced fatty change, vacuolar degeneration and inflammation. These changes were accompanied by activation of NF-κB and induction of inflammatory and cytotoxic mediators leading to increased level of tumor necrosis factor-alpha, enhanced formation of malondialdehyde in the liver followed by drastic alterations in the hepatic antioxidant defense systems. Additionally, nitrite levels and lactate dehydrogenase activities were also significantly elevated on chronic alcohol consumption. Alcohol exposure also increased the number of micronucleated cells indicating that alcohol abuse may again be associated with the nuclear changes. Supplementation with catechin ameliorated the alcohol-induced liver injury by downregulating the endotoxin-mediated activation of initial signalling molecule NF-κB and further going downstream the signalling cascade including tumor necrosis factor-alpha, nitric oxide and reactive oxygen species and by enhancing the antioxidant profile. These observations correlated well with the histological findings. Moreover, a remarkable decrease in the percentage of micronucleated cells was observed with catechin supplementation indicating an apparent protection against alcohol-induced toxicity. These findings suggest that catechin may alleviate experimental alcoholic liver disease by suppressing induction of NF-κB, a key component of signalling pathway, thus forming a pharmacological basis for designing novel therapeutic agents against alcohol induced endotoxin-mediated liver injury.

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Photomicrographs of hematoxylin-eosin stained rat liver sections after alcohol administration.A) Photomicrograph of the normal/control rat liver showing normal liver morphology; B) Photomicrograph of rat liver of catechin per se group showing normal liver morphology; C, D) Photomicrograph of the liver from alcohol-administered rat showing vacuolar degeneration, micro- and macrovesicular fatty change; E) Photomicrograph of the liver from alcohol-administered rat showing portal triaditis with thin fibrous bridges radiating from the portal tract. Liver cells show vacuolar degeneration and microvesicular fatty change; F) Photomicrograph of the liver from alcohol-administered rat supplemented with catechin (Alc + CT) showing mild cytoplasmic vacuolation with no fatty change; G) Photomicrograph of the liver from alcohol-administered rat supplemented with catechin (Alc + CT) showing normal liver morphology.
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pone-0020635-g002: Photomicrographs of hematoxylin-eosin stained rat liver sections after alcohol administration.A) Photomicrograph of the normal/control rat liver showing normal liver morphology; B) Photomicrograph of rat liver of catechin per se group showing normal liver morphology; C, D) Photomicrograph of the liver from alcohol-administered rat showing vacuolar degeneration, micro- and macrovesicular fatty change; E) Photomicrograph of the liver from alcohol-administered rat showing portal triaditis with thin fibrous bridges radiating from the portal tract. Liver cells show vacuolar degeneration and microvesicular fatty change; F) Photomicrograph of the liver from alcohol-administered rat supplemented with catechin (Alc + CT) showing mild cytoplasmic vacuolation with no fatty change; G) Photomicrograph of the liver from alcohol-administered rat supplemented with catechin (Alc + CT) showing normal liver morphology.

Mentions: Histological evaluation did not reveal any morphological alterations in the control group (Figure 2A) and catechin per se group (Figure 2B). The liver sections of alcohol-administered rats showed vacuolar degeneration, micro and macrofollicular fatty changes, focal collection of lymphocytes and vascular congestion. Portal tract inflammation (portal triaditis) was also observed with thin fibrous bridges radiating from the portal tract (Figures 2C–2E). In contrast, the histological examination of tissue sections from alcohol-fed rats supplemented with catechin showed an improvement of liver morphology except for mild vacuolar degeneration. Necrotic cells and fatty change were nearly absent (Figures 2F, 2G).


Catechin suppresses an array of signalling molecules and modulates alcohol-induced endotoxin mediated liver injury in a rat model.

Bharrhan S, Koul A, Chopra K, Rishi P - PLoS ONE (2011)

Photomicrographs of hematoxylin-eosin stained rat liver sections after alcohol administration.A) Photomicrograph of the normal/control rat liver showing normal liver morphology; B) Photomicrograph of rat liver of catechin per se group showing normal liver morphology; C, D) Photomicrograph of the liver from alcohol-administered rat showing vacuolar degeneration, micro- and macrovesicular fatty change; E) Photomicrograph of the liver from alcohol-administered rat showing portal triaditis with thin fibrous bridges radiating from the portal tract. Liver cells show vacuolar degeneration and microvesicular fatty change; F) Photomicrograph of the liver from alcohol-administered rat supplemented with catechin (Alc + CT) showing mild cytoplasmic vacuolation with no fatty change; G) Photomicrograph of the liver from alcohol-administered rat supplemented with catechin (Alc + CT) showing normal liver morphology.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3108820&req=5

pone-0020635-g002: Photomicrographs of hematoxylin-eosin stained rat liver sections after alcohol administration.A) Photomicrograph of the normal/control rat liver showing normal liver morphology; B) Photomicrograph of rat liver of catechin per se group showing normal liver morphology; C, D) Photomicrograph of the liver from alcohol-administered rat showing vacuolar degeneration, micro- and macrovesicular fatty change; E) Photomicrograph of the liver from alcohol-administered rat showing portal triaditis with thin fibrous bridges radiating from the portal tract. Liver cells show vacuolar degeneration and microvesicular fatty change; F) Photomicrograph of the liver from alcohol-administered rat supplemented with catechin (Alc + CT) showing mild cytoplasmic vacuolation with no fatty change; G) Photomicrograph of the liver from alcohol-administered rat supplemented with catechin (Alc + CT) showing normal liver morphology.
Mentions: Histological evaluation did not reveal any morphological alterations in the control group (Figure 2A) and catechin per se group (Figure 2B). The liver sections of alcohol-administered rats showed vacuolar degeneration, micro and macrofollicular fatty changes, focal collection of lymphocytes and vascular congestion. Portal tract inflammation (portal triaditis) was also observed with thin fibrous bridges radiating from the portal tract (Figures 2C–2E). In contrast, the histological examination of tissue sections from alcohol-fed rats supplemented with catechin showed an improvement of liver morphology except for mild vacuolar degeneration. Necrotic cells and fatty change were nearly absent (Figures 2F, 2G).

Bottom Line: Additionally, nitrite levels and lactate dehydrogenase activities were also significantly elevated on chronic alcohol consumption.Alcohol exposure also increased the number of micronucleated cells indicating that alcohol abuse may again be associated with the nuclear changes.Moreover, a remarkable decrease in the percentage of micronucleated cells was observed with catechin supplementation indicating an apparent protection against alcohol-induced toxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Basic Medical Sciences Block, Panjab University, Chandigarh, India.

ABSTRACT
Induction of nuclear factor kappa B (NF-κB)-mediated gene expression has been implicated in the pathogenesis of alcoholic liver disease through enhanced production of reactive oxygen species and pro-inflammatory mediators. The present study was carried out to investigate the role of catechin as a chain breaking inhibitor against experimental alcoholic liver injury. Rats were administered 35% v/v ethanol orally at a dose of 10 g/Kg/day for two weeks, followed by 14 g/Kg/day for 10 weeks. Catechin (50 mg/Kg) was co-supplemented after 4 weeks of alcohol treatment till the end of the dosing period. Following chronic alcohol exposure, rats developed endotoxemia and severe pathological changes in the liver such as pronounced fatty change, vacuolar degeneration and inflammation. These changes were accompanied by activation of NF-κB and induction of inflammatory and cytotoxic mediators leading to increased level of tumor necrosis factor-alpha, enhanced formation of malondialdehyde in the liver followed by drastic alterations in the hepatic antioxidant defense systems. Additionally, nitrite levels and lactate dehydrogenase activities were also significantly elevated on chronic alcohol consumption. Alcohol exposure also increased the number of micronucleated cells indicating that alcohol abuse may again be associated with the nuclear changes. Supplementation with catechin ameliorated the alcohol-induced liver injury by downregulating the endotoxin-mediated activation of initial signalling molecule NF-κB and further going downstream the signalling cascade including tumor necrosis factor-alpha, nitric oxide and reactive oxygen species and by enhancing the antioxidant profile. These observations correlated well with the histological findings. Moreover, a remarkable decrease in the percentage of micronucleated cells was observed with catechin supplementation indicating an apparent protection against alcohol-induced toxicity. These findings suggest that catechin may alleviate experimental alcoholic liver disease by suppressing induction of NF-κB, a key component of signalling pathway, thus forming a pharmacological basis for designing novel therapeutic agents against alcohol induced endotoxin-mediated liver injury.

Show MeSH
Related in: MedlinePlus