Quercetin Administration Ameliorates Pulmonary Complications of Cirrhosis in Rats

Abstract

In the hepatopulmonary syndrome (HPS), a common complication of liver cirrhosis, pulmonary endothelial endothelin B (ETB) receptor overexpression, enhanced endothelial nitric oxide (NO) synthase (eNOS)-derived NO production, and increases in pulmonary inducible NO synthase (iNOS) and heme oxygenase (HO-1) are important factors in the development of vasodilatation. These changes may be influenced by redox-sensitive signaling pathways, including nuclear factor-kappaB (NF-kappaB). In this study, our aim was to evaluate the effects of the flavonoid antioxidant quercetin on the development of HPS in rats with common bile duct ligation (CBDL). Rats were divided into the following 4 groups: rats subjected to CBDL, Sham (rats subjected to simulated CBDL), quercetin-treated sham, and quercetin-treated CBDL. Quercetin (50 mg/kg) was administered for 2 wk starting on d 14 after surgery. Increased NO production, overexpression of iNOS, eNOS, HO-1, and ETB-receptor and activation of NF-kappaB were observed in lung of CBDL rats. Quercetin inhibited oxidative stress, NF-kappaB activation, and the expression of different pulmonary mediators involved in HPS. Quercetin also ameliorated liver injury and reduced the expression of hepatic endothelin-1 and HO-1 in untreated cirrhotic rats. Our findings suggest that quercetin administered after the onset of hepatic injury significantly ameliorates pulmonary complications in CBDL rats and that limitation of cirrhotic evolution contributes to this effect.

Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation

“…These findings were associated with a marked inhibition of HFD-induced TLR-4 expression at transcriptional level and the modulation of TLR-4-NF-B signaling pathway activation by quercetin, and a downregulation of TNF- and IL-6 gene expression, confirming its well-known anti-inflammatory capacity [5,26,59,60]. TNF- and IL-6 play a key role in glucose homeostasis impairment associated with HFD [61], suggesting that proinflammatory cytokines blockage by quercetin contributes to its anti-insulin resistance properties.…”

Protective effect of quercetin on liver damage induced by biliary obstruction in rats

“…TGF b was 2.9 fold greater in untreated BDL rats compared to control rats. Administration of QE to cirrhotic rats with established bridging fibrosis resulted in 18-28% lower expression levels compared to untreated BDL rats (Tieppo et al 2009). We analyzed TGF-b1 as a target of QE to prevent fibrosis.…”

“…In BDL-QE rats, fibrosis was greatly reduced (Tieppo et al 2009). Likewise Tieppo et al andAksu et al's (2009, 2009) studies, we have found in our study that the positive stainings for a-SMA were greatly increased especially in vascular smooth muscle cells and sinusoids and also in the cells of portal ducts, fibrotic septa, perisinuses and around the proliferated bile ducts. The a-SMA positive cells in the BDL group were observed to be reduced with the QE treatment.…”

Protective effects of thymoquinone against cholestatic oxidative stress and hepatic damage after biliary obstruction in rats

“…In BDL-QE rats, fibrosis was greatly reduced (Tieppo et al 2009). Likewise Tieppo et al andAksu et al's (2009,2010) studies, we have found in our study that the positive stainings for a-SMA were greatly increased especially in vascular smooth muscle cells and sinusoids and also in the cells of portal ducts, fibrotic septa, perisinuses and around the proliferated bile ducts. The a-SMA positive cells in the BDL group were observed to be reduced with the TQ treatment.…”