Interrelation of liver vascularity to non-alcoholic fatty liver through a comparative study of the vasodilator effect of carvedilol or nicorandil in rats

Soliman, Ghada Farouk; Rashed, Laila Ahmed; Morsi, Heba; Ibrahim, Walaa; Abdallah, Hanan; Bastawy, Nermeen; Maksoud, Omnia Mohamed Abdel

doi:10.1016/j.lfs.2019.02.057

Cited by 8 publications

(5 citation statements)

References 40 publications

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“…Consistent with our findings, Soliman et al (2019) recently showed that carvedilol reduced hepatic α-smooth muscle actin immunopositivity (an indicator of stellate cells activation), malondialdehyde (oxidative stress marker), and triglyceride content in rats with diet-induced liver steatosis. We successfully reproduced the reducing effect of carvedilol on the excessive cumulation of triglycerides in the liver of NASH mice.…”

Section: Discussionsupporting

confidence: 92%

“…It also exhibits antifibrotic activity in animal models of liver injury induced by ethanol ( Hakucho et al , 2014 ), carbon tetrachloride ( Ling et al , 2019 ), or bile duct ligation ( Tian et al , 2017 ). In addition, amelioration of liver impairment by carvedilol was described in a rat model of liver steatosis ( Soliman et al , 2019 ); however, the efficacy of carvedilol treatment in nonalcoholic steatohepatitis (NASH), which is a more severe form of fatty liver, remains unclear. In contrast, treatment with propranolol, a β-adrenoreceptor antagonist, worsened liver injury in a mouse NASH model ( McKee et al , 2013 ).…”

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confidence: 99%

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Carvedilol impairs bile acid homeostasis in mice: implication for nonalcoholic steatohepatitis

Lastuvkova,

Nova,

Hroch

et al. 2023

Toxicological Sciences

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Carvedilol is a widely used beta-adrenoreceptor antagonist for multiple cardiovascular indications; however, it may induce cholestasis in patients, but the mechanism for this effect is unclear. Carvedilol also prevents the development of various forms of experimental liver injury, but its effect on nonalcoholic steatohepatitis (NASH) is largely unknown. In this study, we determined the effect of carvedilol (10 mg/kg/day p.o.) on bile formation and bile acid (BA) turnover in male C57BL/6 mice consuming either a chow diet or a western-type NASH-inducing diet. BAs were profiled by LC-MS and BA-related enzymes, transporters, and regulators were evaluated by western blot analysis and qRT-PCR. In chow diet-fed mice, carvedilol increased plasma concentrations of BAs resulting from reduced BA uptake to hepatocytes via Ntcp transporter downregulation. Inhibition of the β-adrenoreceptor-cAMP-Epac1-Ntcp pathway by carvedilol may be the post-transcriptional mechanism underlying this effect. In contrast, carvedilol did not worsen the deterioration of BA homeostasis accompanying NASH; however, it shifted the spectra of BAs toward more hydrophilic and less toxic α-muricholic and hyocholic acids. This positive effect of carvedilol was associated with a significant attenuation of liver steatosis, inflammation, and fibrosis in NASH mice. In conclusion, our results indicate that carvedilol may increase BAs in plasma by modifying their liver transport. In addition, carvedilol provided significant hepatoprotection in a NASH murine model without worsening BA accumulation. These data suggest beneficial effects of carvedilol in patients at high risk for developing NASH.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Carvedilol impairs bile acid homeostasis in mice: implication for nonalcoholic steatohepatitis

Lastuvkova,

Nova,

Hroch

et al. 2023

Toxicological Sciences

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“…The World Health Organization reported approximately 2.6 million deaths due to hypercholesterolemia [2]. Hypercholesterolemia has multiple significant consequences on different physiological systems, and is one of the major risk factors for several health problems, including ischemic heart diseases, fatty liver, and kidney diseases [3][4][5]. Altered cardiac systolic and diastolic functions as well as contractile dysfunction have been reported in rodents that were fed a high-cholesterol diet (HCD) [6].…”

Section: Introductionmentioning

confidence: 99%

Baicalein Neutralizes Hypercholesterolemia-Induced Aggravation of Oxidative Injury in Rats

Alsaad¹,

Mohany²,

Almalki³

et al. 2020

Int. J. Med. Sci.

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Hypercholesterolemia is a major risk factor for several cardiovascular and metabolic diseases as it triggers oxidative and pro-inflammatory cascades. Baicalein (BL) is a natural flavone with multiple therapeutic properties. The present study aimed to evaluate the potential protective effect of BL supplementation in hypercholesterolaemic rats. Rats were fed a high-cholesterol diet (HCD) for six weeks and then orally administered BL at two doses (25 and 50 mg/kg body weight/day) for four weeks. Serum lipids, liver enzymes, cardiac enzymes, renal markers, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-10 (IL-10), caspase-3, nitric oxide (NO) and prostaglandin-2 (PGE-2) were measured. In renal, hepatic, and cardiac tissues, thiobarbituric acid-reactive (TBARS) substance, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured. The altered levels of lipoproteins, aminotransferases, creatine kinases, and urea in hypercholesterolemic animals were significantly corrected by BL. Inflammatory and apoptotic biomarkers were also markedly attenuated in the HCD group following BL treatment. Hypercholesterolemia considerably induced the lipid peroxidation product, TBARS, and oxidative radicals in cardiac, hepatic, and renal tissues, which were attenuated by BL treatment, particularly, at the 50 mg/kg/day dose. BL enhanced the activities of superoxide dismutase, catalase, and glutathione peroxidase that were suppressed by HCD. Histological alterations induced by cholesterol overload in cardiac, hepatic, and renal tissues were ameliorated by BL supplementation. Our results show that the BL treatments (25 and 50 mg/kg/day) to HCD fed rats improved all the altered parameters. These results demonstrate that BL treatment improves cardiac, renal and hepatic dysfunctions in hypercholesterolaemic rats by activation of cellular antioxidant enzymes and/or suppression of inflammatory cytokines.

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“…Hypercholesterolemia has multiple significant consequences on different physiological systems, and is one of the major risk factors for several health problems, including ischemic heart diseases, fatty liver, and kidney diseases (3)(4)(5). Altered cardiac systolic and diastolic functions as well as contractile dysfunction have been reported in rodents that were fed a high-cholesterol diet (HCD) (6).…”

Section: Introductionmentioning

confidence: 99%

Baicalein neutralizes hypercholesterolemia-induced aggravation of oxidative injury in rats

Alsaad

Almalki

Almutham

et al. 2020

Preprint

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Background: Hypercholesterolemia is a major risk factor for several cardiovascular and metabolic diseases as it triggers oxidative and pro-inflammatory cascades. Baicalein (BL) is a natural flavone with multiple therapeutic properties. The present study aimed to evaluate the potential protective effect of BL supplementation in hypercholesterolemic rats. Methods: Rats were fed a high-cholesterol diet (HCD) for six weeks and then orally administered BL at two doses (25 and 50 mg/kg body weight/day) for four weeks. Serum lipids, liver enzymes, cardiac enzymes, renal markers, tumor necrosis factor-α, interleukin-6, interleukin-1β, interleukin-10, caspase-3, nitric oxide and prostaglandin-2 were measured. In renal, hepatic, and cardiac tissues, thiobarbituric acid-reactive substance, glutathione, superoxide dismutase, catalase, and glutathione peroxidase activities were measured. Results: The altered levels of lipoproteins, aminotransferases, creatine kinases, and urea in hypercholesterolemic animals were significantly corrected by BL. Inflammatory and apoptotic biomarkers were also markedly attenuated in the HCD group following BL treatment. Hypercholesterolemia considerably induced the lipid peroxidation product, TBARS, and oxidative radicals in cardiac, hepatic, and renal tissues, which were attenuated by BL treatment, particularly, at the 50 mg/kg/day dose. BL enhanced the activities of superoxide dismutase, catalase, and glutathione peroxidase that were suppressed by HCD. Histological alterations induced by cholesterol overload in cardiac, hepatic, and renal tissues were ameliorated by BL supplementation. Conclusions: Our results show that the co-administration of BL (25 and 50 mg/kg/day) in HCD rats improved all the altered parameters. Activation of cellular antioxidant enzymes and/or suppression of inflammatory cytokines may be involved in these prominent effects.

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Interrelation of liver vascularity to non-alcoholic fatty liver through a comparative study of the vasodilator effect of carvedilol or nicorandil in rats

Cited by 8 publications

References 40 publications

Carvedilol impairs bile acid homeostasis in mice: implication for nonalcoholic steatohepatitis

Carvedilol impairs bile acid homeostasis in mice: implication for nonalcoholic steatohepatitis

Baicalein Neutralizes Hypercholesterolemia-Induced Aggravation of Oxidative Injury in Rats

Baicalein neutralizes hypercholesterolemia-induced aggravation of oxidative injury in rats

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