Carvedilol Attenuates the Progression of Alcohol Fatty Liver Disease in Rats

Abstract

Ethanol metabolism-induced lipogenesis may trigger the SNS-activated HSCs feedback loop, and then induct the activated HSCs and the activated HSCs-derived TNF-α, the mediator of lipogenesis, overproduction. Carvedilol may block this feedback loop via antisympathetic activity and demonstrate its preventive role on the development of hepatosteatosis in rat with AFLD.

Carvedilol improves ethanol‐induced liver injury via modifying the interaction between oxidative stress and sympathetic hyperactivity in rats

“…Studies have reported that chronic alcohol consumption induced liver injury associated with sympathetic hyperactivity, and implicated ROS in the pathogenesis of activation of the SNS, which may affect liver injury by modulating cellular oxidative damage . The major source of ROS is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an enzyme that can be activated during ethanol metabolism, leading to the production of superoxide anions (O – 2 ) in the liver.…”

“…The rats were housed at constant temperature (22 ± 2°C) and humidity (45 ± 5%), and exposed to a standard light : dark cycle (12:12 h) at the Institute of Laboratory Animals, Yamaguchi University. The same ethanol consumption protocol was used as in our previous liver study . In brief, 52 rats were housed individually, assigned to a group randomly, and fed a nutritionally adequate liquid diet for 49 days.…”

“…Carvedilol, which can block the SNS via β1‐, β2‐ and α1‐adrenoreceptors, has been shown to provide greater benefit than traditional beta‐blockers because of its antioxidant, anti‐inflammatory and antifibrotic properties in the cardiac studies . Carvedilol also exerted its antifibrotic effects by amelioration of oxidative stress in carbon tetrachloride‐induced hepatotoxicity, and its suppressing effects on the HSC‐derived lipogenesis‐ and fibrogenesis‐related mediators' production and the body insulin resistance . Insulin receptor substrate 1 (IRS‐1) is a critical element in the insulin‐signaling pathways, and mutations in the Irs‐1 gene have been reported to have a role in the impairment of hepatic insulin signaling in rats with alcoholic liver disease .…”

Liver innervation and hepatic function: new insights

“…Furthermore, the SNS may contribute at least partly to the sensitizing effect of ethanol on lipopolysaccharide-induced liver injury in mice and concurrent administration of the beta-blocker propranolol with ethanol results in attenuation of this effect [62]. Carvedilol, an agent, which can block the SNS completely via b1, b2, and a1 adrenergic receptors, may have a protective role against development of hepatosteatosis in rats with alcohol fatty liver disease [63]. On the other hand, hepatic sympathetic innervation is protective against Fas-mediated fulminant hepatitis.…”

Carvedilol Could Ameliorate Acetaminophen Overdose Hepatotoxicity. Endogenous H2S Contributes Such Effect: A Comparative Biochemical Evaluation

“…CVD provides greater cardiovascular benefits than traditional β-blockers that have been attributed to its antioxidant, anti-inflammatory, and anti-fibrotic properties [9]. The anti-fibrotic effects of CVD have been associated with the amelioration of oxidative stress in carbon tetrachloride-induced hepatotoxicity model [10] and suppression of hepatic satellite cell-derived lipogenesis-and fibrogenesis-related mediators [11].…”