Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

Vodovotz, Yoram; Kim, Peter K.M.; Bagci, Elife Zerrin; Ermentrout, Bard; Chow, Carson C.; Bahar, İvet; Billiar, Timothy R.

doi:10.2174/1566524043359944

Cited by 70 publications

(50 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well known that NO and PGE2 are main macrophage-derived inflammatory mediators. 50,55,56 Furthermore, it has been reported that TNF-α, IL-6 and IL-1β is an important inflammatory cytokine. Therefore, it has been thought suppression on TNF-α, IL-6, IL-1β and NO is a good strategy to reduce inflammation.…”

Section: Resultsmentioning

confidence: 99%

In vitro study of Myristica fragrans seed (Nutmeg) ethanolic extract and quercetin compound as anti-inflammatory agent

et al. 2015

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

In vitro study of Myristica fragrans seed (Nutmeg) ethanolic extract and quercetin compound as anti-inflammatory agent

et al. 2015

View full text Add to dashboard Cite

“…NF-κB is also involved in the regulation of COX-2 and iNOS gene expression by binding to their promoter regions [28] . COX-2 and iNOS exert a prominent role under inflammatory conditions by producing prostaglandins and NO · , respectively [29,30] . Thus, the antiinflammatory effect of quercetin and rutin in CCl 4 -injured liver could be attributed to the inhibition of the NF-κB pathway, which is in agreement with previous findings [31] .…”

Section: Discussionmentioning

confidence: 99%

Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB/cN mice

et al. 2012

View full text Add to dashboard Cite

Aim: To investigate the mechanisms underlying the protective effects of quercetin-rutinoside (rutin) and its aglycone quercetin against CCl 4 -induced liver damage in mice. Methods: BALB/cN mice were intraperitoneally administered rutin (10, 50, and 150 mg/kg) or quercetin (50 mg/kg) once daily for 5 consecutive days, followed by the intraperitoneal injection of CCl 4 in olive oil (2 mL/kg, 10% v/v). The animals were sacrificed 24 h later. Blood was collected for measuring the activities of ALT and AST, and the liver was excised for assessing Cu/Zn superoxide dismutase (SOD) activity, GSH and protein concentrations and also for immunoblotting. Portions of the livers were used for histology and immunohistochemistry. Results: Pretreatment with rutin and, to a lesser extent, with quercetin significantly reduced the activity of plasma transaminases and improved the histological signs of acute liver damage in CCl 4 -intoxicated mice. Quercetin prevented the decrease in Cu/Zn SOD activity in CCl 4 -intoxicated mice more potently than rutin. However, it was less effective in the suppression of nitrotyrosine formation. Quercetin and, to a lesser extent, rutin attenuated the inflammation in the liver by down-regulating the CCl 4 -induced activation of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) and cyclooxygenase (COX-2). The expression of inducible nitric oxide synthase (iNOS) was more potently suppressed by rutin than by quercetin. Treatment with both flavonoids significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers, although quercetin was less effective than rutin at an equivalent dose. Quercetin more potently suppressed the expression of transforming growth factor-β1 (TGF-β1) than rutin. Conclusion: Rutin exerts stronger protection against nitrosative stress and hepatocellular damage but has weaker antioxidant and antiinflammatory activities and antifibrotic potential than quercetin, which may be attributed to the presence of a rutinoside moiety in position 3 of the C ring.

show abstract

“…An induction of the NOS2 expression has also been seen after hepatocytes are exposed to woodchuck hepatitis virus surface antigen (Liu et al, 1994). In patients with HBV or HCV infection, a consistent upregulation of hepatic NOS2 has been shown (Kane et al, 1997;Vodovotz et al, 2004).…”

Section: Figurementioning

confidence: 90%

“…In contrast, NOS2 (also called iNOS) requires induction generally, but is able to produce NO concentrations in the micromolar range (reviewed by Ambs et al, 1997). NOS2 gene expression can be induced by bacterial endotoxins, proinflammatory cytokines or hypoxia (Wild et al, 1986;Nussler et al, 1992;Lombard and Guarente, 2000) in many cell types, including macrophages (Xie et al, 1992) and hepatocytes (Mowat et al, 1990;Lombard and Guarente, 2000;Vodovotz et al, 2004) as well as in a variety of human tumors (reviewed by Ambs et al, 1997). During chronic viral hepatitis, the upregulation of certain proinflammatory cytokines, like tumor necrosis factor-a (TNF-a) and interferon-g (IFN-g), has been repeatedly demonstrated (Gonzalez-Amaro et al, 1994;Mihm et al, 1996).…”

Section: Figurementioning

confidence: 99%

TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer

et al. 2007

View full text Add to dashboard Cite

Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

Cited by 70 publications

References 107 publications

In vitro study of Myristica fragrans seed (Nutmeg) ethanolic extract and quercetin compound as anti-inflammatory agent

In vitro study of Myristica fragrans seed (Nutmeg) ethanolic extract and quercetin compound as anti-inflammatory agent

Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB/cN mice

TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer

Contact Info

Product

Resources

About