Effects of Caffeine Treatment on Hepatopulmonary Syndrome in Biliary Cirrhotic Rats

Abstract

Hepatopulmonary syndrome (HPS) is a lethal complication of cirrhosis characterized by hypoxia and overt intrapulmonary shunting. In this study, we investigated the effect of caffeine in rats with common bile duct ligation (CBDL)-induced liver cirrhosis and HPS. CBDL rats were randomly allocated to receive caffeine or vehicle for 14 days. On the 28th day after CBDL, mortality rate, hemodynamics, liver, and renal biochemistry parameters and arterial blood gas analysis were evaluated. Lung and liver were dissected for the evaluation of inflammation, angiogenesis and protein expressions. In another series with parallel groups, the intrapulmonary shunting was determined. Caffeine significantly reduced portal pressure (caffeine vs. control: 10.0 ± 3.7 vs. 17.0 ± 8.1 mmHg, p < 0.05) in CBDL rats. The mortality rate, mean arterial pressure, biochemistry data and hypoxia were similar between caffeine-treated and control groups. Caffeine alleviated liver fibrosis and intrahepatic angiogenesis but intrapulmonary inflammation and angiogenesis were not ameliorated. The hepatic VEGF/Rho-A protein expressions were down-regulated but the pulmonary inflammation- and angiogenesis-related protein expressions were not significantly altered by caffeine. Caffeine did not reduce the intrapulmonary shunting, either. Caffeine has been shown to significantly improve liver fibrosis, intrahepatic angiogenesis and portal hypertension in cirrhotic rats, however, it does not ameliorate HPS.

Lycopene treatment improves intrahepatic fibrosis and attenuates pathological angiogenesis in biliary cirrhotic rats

“…To determine intrahepatic angiogenesis, immunohistochemical staining with anti-CD31 antibodies (1:200, Serotec and Pharmingen, San Diego, CA, USA) was performed, 14 using the primary antibodies against CD-31 followed by biotinylated anti-mouse IgG (H+L) (Vector Laboratories, Burlingame, CA, USA) as the second antibody.…”

Caffeine and bronchopulmonary dysplasia: Clinical benefits and the mechanisms involved

“…However, caffeine may have no significant effects on the expression of lung angiogenesisrelated protein in animal models of inflammation. 98 One possible explanation is that the effect of caffeine on angiogenic proteins may be influenced by many factors.…”

“…Caffeine act on the A2AR of endothelial cells to regulate vaso‐obliteration and vaso‐proliferation 97 ; these processes may represent potential mechanisms underlying the pulmonary vascular protection provided by caffeine. However, caffeine may have no significant effects on the expression of lung angiogenesis‐related protein in animal models of inflammation 98 . One possible explanation is that the effect of caffeine on angiogenic proteins may be influenced by many factors.…”

Effects of PCSK-9 Inhibition by Alirocumab Treatments on Biliary Cirrhotic Rats

“…Superior mesentery arterial resistance (SMAR, mmHg/mL/min/100 g BW) was calculated by (MAP-PP)/superior mesentery artery flow (SMAf) per 100 g BW. The measurements of portal venous blood flow (PVf), superior mesenteric artery blood flow (SMAf) and resistance (SMAR) were performed [39]. The PVf (mL/min) and SMAf (mL/min) were measured using a nonconstrictive perivascular ultrasonic transit-time flow probe (lRB, 1-mm diameter; Transonic Systems, Ithaca, NY, USA).…”

“…Sections were counterstained with Mayer's hematoxylin. Intrahepatic angiogenesis was assessed by counting the number of CD31-positive staining cells using light microscopy [39].…”