Down-regulation of NF-κB signalling by polyphenolic compounds prevents endotoxin-induced liver injury in a rat model.
Activation of NF-κB has been reported to play a key role in causing endotoxin-induced hepatic damage through enhanced production of reactive oxygen species and pro-inflammatory mediators. In this context, the potential of polyphenolic phytochemicals in preventing endotoxin-induced liver damage remains unclear. Here, we demonstrate that catechin and quercetin have the potential to down-regulate the initial signalling molecule NF-κB which may further inhibit the downstream cascade including TNF-α and NO. These results were confirmed using N-nitro-L-arginine methyl ester (L-NAME), the inhibitor of inducible nitric oxide synthase (iNOS) along with the biochemical and histological alterations occurring in the presence and absence of supplementation with both the polyphenols. However, catechin was found to be more effective than quercetin against endotoxin-induced liver injury. These findings suggest that these polyphenols may form a pharmacological basis for designing a therapeutic agent against endotoxin-mediated oxidative damage.
Department of Microbiology, Basic Medical Sciences Block, Panjab University, Chandigarh, India.
Sushma
S
Bharrhan
Kanwaljit
K
Chopra
Sunil K
SK
Arora
Jaideep S
JS
Toor
Praveen
P
Rishi
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects; D002392:Catechin / Q000008:administration & dosage* / Q000009:adverse effects; D004195:Disease Models, Animal; D004731:Endotoxins / Q000276:immunology* / Q000633:toxicity; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects; D059808:Polyphenols / Q000627:therapeutic use*; D011794:Quercetin / Q000008:administration & dosage* / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000150:complications; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D004731:Endotoxins; D016328:NF-kappa B; D059808:Polyphenols; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002392:Catechin; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II; D019331:NG-Nitroarginine Methyl Ester