Caffeine prevents experimental liver fibrosis by blocking the expression of TGF-β

Arauz, Jonathan; Zarco, Natanael; Segovia, José; Shibayama, Mineko; Tsutsumi, Vı́ctor; Muriel, Pablo

doi:10.1097/meg.0b013e3283644e26

Cited by 61 publications

(52 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the development of LC, HSCs and LSECs play important roles . Caffeine decreased expression of alpha‐smooth muscle actin in TAA‐induced cirrhotic rats .…”

Section: Discussionmentioning

confidence: 99%

Caffeine ameliorates hemodynamic derangements and portosystemic collaterals in cirrhotic rats

Hsu

Lee

Wang³

et al. 2015

Hepatology

View full text Add to dashboard Cite

Portal hypertension (PH), a pathophysiological derangement of liver cirrhosis, is characterized by hyperdynamic circulation, angiogenesis, and portosystemic collaterals. These may lead to lethal complications, such as variceal bleeding. Caffeine has been noted for its effects on liver inflammation, fibrogenesis, and vasoreactiveness. However, the relevant influences of caffeine in cirrhosis and PH have not been addressed. Spraque-Dawley rats with common bile duct ligation-induced cirrhosis or sham operation received prophylactic or therapeutic caffeine treatment (50 mg/kg/day, the first or 15th day since operation, respectively) for 28 days. Compared to vehicle (distilled water), caffeine decreased cardiac index, increased systemic vascular resistance, reduced portal pressure (PP), superior mesenteric artery flow, mesenteric vascular density, portosystemic shunting (PSS), intrahepatic angiogenesis, and fibrosis without affecting liver and renal biochemistry. The beneficial effects were reversed by selective adenosine A1 agonist N6-cyclopentyladenosine (CPA) or A2A agonist GCS21680. Both prophylactic and therapeutic caffeine treatment decreased portal resistance and PP in thioacetamide (200mg/kg, thrice-weekly for 8 weeks)-induced cirrhotic rats. Caffeine down-regulated endothelial nitric oxide synthase, vascular endothelial growth factor (VEGF), phospho-VEGFR2, and phospho-Akt mesenteric protein expression. Caffeine adversely affected viability of hepatic stellate and sinusoidal endothelial cells, which was reversed by CPA and GCS21680. On the other hand, caffeine did not modify vascular response to vasoconstrictors in splanchnic, hepatic, and collateral vascular beds. Conclusions: Caffeine decreased PP, ameliorated hyperdynamic circulation, PSS, mesenteric angiogenesis, hepatic angiogenesis, and fibrosis in cirrhotic rats. Caffeine may be a feasible candidate to ameliorate PH-related complications in cirrhosis. (HEPATOLOGY 2015;61:1672-1684

show abstract

“…During the development of LC, HSCs and LSECs play important roles . Caffeine decreased expression of alpha‐smooth muscle actin in TAA‐induced cirrhotic rats .…”

Section: Discussionmentioning

confidence: 99%

Caffeine ameliorates hemodynamic derangements and portosystemic collaterals in cirrhotic rats

Hsu

Lee

Wang³

et al. 2015

Hepatology

View full text Add to dashboard Cite

show abstract

“…[14] TGF-β1 could be secreted by active HSCs and their cell line, HSC-T6 cells. TGF-β1 could induce the activity of many signaling pathways such as MAPK and Wnt through a Smad3-mediated signaling cascade.…”

Section: Discussionmentioning

confidence: 99%

Anti-fibrosis effects of Huisheng oral solution in CCl ₄ -induced hepatic fibrosis in rat

Zhu

et al. 2014

Indian J Pharmacol

View full text Add to dashboard Cite

Aim:Some gradient of Huisheng oral solution (HOS) has been reported to have anti-fibrosis activity. This study was designed to investigate whether HOS could inhibit liver fibrosis and to elucidate its molecular mechanism of action.Materials and Methods:Hepatic fibrosis model in rat was induced by subcutaneous injection of CCl4. Rats in the treatment group were administrated with HOS intragastrically. Hematoxylin and eosin (H and E) staining and Masson's trichrome staining were used to examine the changes in liver pathology. Levels of ALT, AST, LDH, hyaluronic acid (HA) and laminin (LN) in serum and hydroxyproline (Hyp) in liver were detected by biochemical examination and radioimmunoassay, respectively. The expression and distribution of Smad3, TGF-β1, α-SMA and TIMP-1 were observed and the active TGF-β1 was tested.Results:Our data demonstrated that HOS alleviated CCl4-induced collagen deposition in liver tissue, improved liver condition and liver function in rats. HOS also significantly reduced the expression and distribution of Smad3, TGF-β1, α-SMA and TIMP-1 as well as decreased active TGF-β1.Conclusions:This study revealed that HOS attenuates the development of liver fibrosis through suppressing the TGF-β1 pathway. It provides us a new approach to treatment of liver fibrosis.

show abstract

“…Moderate caffeine intake (400 mg of caffeine) does not increase arrhythmia risk acutely in healthy individuals [21,22]. Although several studies showed that caffeine reduced hepatic fibrosis by interfering with transforming growth factor b signaling [23][24][25], limited data are available about its cardiac antifibrosis effect which, if it occurs, might be responsible for its protective effect against arrhythmias [26,27].…”

Section: Discussionmentioning

confidence: 99%

Does Caffeine Consumption Increase the Risk of New-Onset Atrial Fibrillation?

Abdelfattah

Kamran²,

Lazar³

et al. 2018

Cardiology

View full text Add to dashboard Cite

Objective: Caffeine has been considered a trigger for atrial fibrillation (AF). We conducted a meta-analysis including a dose-response analysis to assess the relationship between caffeine consumed and incidence of AF. Methods: Data from selected studies represented 176,675 subjects (AF in 9,987 [5.7%]). Caffeine content varied widely, ranging from 40 to 180 mg per cup of coffee. For purposes of the calculations in this study, we assumed 140 mg of caffeine in a standard 12-oz cup of coffee. Results: No significant difference was found in AF incidence when the subjects consuming less than 2 cups of coffee per day were compared to subjects with higher consumption, 1.068 (0.937–1.216). The risk of AF was higher among subjects consuming less than 2 cups of coffee daily when compared to higher daily consumption subjects. A lower incidence of AF was found among people consuming more than 436 mg daily. Conclusion: The incidence of AF is not increased by coffee consumption. In fact, we found a lower incidence of AF when caffeine consumption exceeded 436 mg/day. Therefore, based on available evidence there is no association between caffeine intake and AF risk.

show abstract

Caffeine prevents experimental liver fibrosis by blocking the expression of TGF-β

Cited by 61 publications

References 36 publications

Caffeine ameliorates hemodynamic derangements and portosystemic collaterals in cirrhotic rats

Caffeine ameliorates hemodynamic derangements and portosystemic collaterals in cirrhotic rats

Anti-fibrosis effects of Huisheng oral solution in CCl ₄ -induced hepatic fibrosis in rat

Does Caffeine Consumption Increase the Risk of New-Onset Atrial Fibrillation?

Contact Info

Product

Resources

About

Caffeine prevents experimental liver fibrosis by blocking the expression of TGF-β

Cited by 61 publications

References 36 publications

Caffeine ameliorates hemodynamic derangements and portosystemic collaterals in cirrhotic rats

Caffeine ameliorates hemodynamic derangements and portosystemic collaterals in cirrhotic rats

Anti-fibrosis effects of Huisheng oral solution in CCl 4 -induced hepatic fibrosis in rat

Does Caffeine Consumption Increase the Risk of New-Onset Atrial Fibrillation?

Contact Info

Product

Resources

About

Anti-fibrosis effects of Huisheng oral solution in CCl ₄ -induced hepatic fibrosis in rat