CardiacProtective effects of naringenin in cardiorenal syndrome
Introduction
The heart has a complicated and bidirectional interrelationship with the kidneys.1 Impairment of one organ could influence the other one, which in turn results in damage of both organs. This phenomenon is defined as cardiorenal syndrome.1 Cardiovascular morbidity is considered to be the major cause of death among those patients with impaired renal function.2, 3 In turn, myocardial infarction has been reported to result in injury of renal function.4 Therefore, impairment of renal and cardiovascular function forms a vicious cycle through cardiorenal interaction, leading to increase of morbidity and mortality in patients with cardiovascular and renal diseases. Numerous literature has suggested that the renin-angiotensin-aldosterone system, sympathetic nervous system, endothelial dysfunction, oxidative stress, and inflammation are involved in cardiorenal syndrome.5, 6, 7, 8, 9, 10
Naringenin (NG) is a naturally occurring flavonoid which is widely distributed in grapefruit, lemon, and tomato.11 NG possesses various biological and pharmacologic properties, including antioxidant, anti-inflammatory, antithrombotic, anticarcinogenic, antidiarrheal, and antiulcer activities. In the last decade, several studies have shown that NG exhibits cardiovascular and renal protective effects. Subburaman et al. showed that NG protected against doxorubicin-induced cardiotoxicity in a rat model.12 Karuppagounder et al. found that NG-ameliorated daunorubicin-induced nephrotoxicity through inhibition of inflammation.13 However, whether NG could improve the outcomes of cardiorenal syndrome is unclear.
In the present study, we sought to assess whether NG could improve cardiac and renal function in a rat model of cardiorenal syndrome. We found that NG attenuated cardiac remodeling and cardiac dysfunction in rats with cardiorenal syndrome. NG decreased lipid profiles, inhibited cardiac inflammation, and reduced oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) and/or catalytic subunit of γ-glutamylcysteine ligase (GCLc)-regulated glutathione (GSH) synthesis contributed to NG-induced antioxidant effects and thus the cardioprotective effects against cardiorenal syndrome.
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Animal treatment
All the experimental procedures were approved by the Animal Ethnics Committee of the Yan'an University. All experiments were carried out in accordance with the approved guidelines. 80 Male Sprague Dawley rats (180-220 g) were purchased from Laboratory Animal Centre of Yan'an University. The animals were housed under conditions of controlled temperature (23 ± 2°C) and humidity (60%) with 12-h light and/or dark cycles.
Rat model of cardiorenal syndrome was established as previously reported.14, 15
NG attenuated cardiac remodeling and dysfunction in rats with cardiorenal syndrome
The administration of NG significantly and dose dependently decreased LVW, increased BW, and decreased LVW/BW, compared with that of rats with cardiorenal syndrome (Table 1). The results indicated that NG attenuated cardiac remodeling in rats with cardiorenal syndrome. Concentration of Scr in rats with cardiorenal syndrome was decreased from 88.7 ± 9.8 μmol/L to 72.1 ± 8.5 μmol/L and 59.6 ± 9.9 μmol/L by low dose of NG and high dose of NG (P = 0.006), respectively (Table 2). NG significantly
Discussion
Flavonoids are naturally occurring compounds that have a wide variety of biological properties. NG, a flavanone, is one of the major antioxidants that are present in citrus fruits. Numerous literature has shown that NG possesses cardio and renal protective effects in vivo and in vitro.12, 19, 20, 21, 22 Those findings provide a possibility that NG may have beneficial effects for cardiorenal syndrome. In the present study, we examined the effect of NG in rats with cardiorenal syndrome. We found
Acknowledgment
Author contributions: A.G. and Y.L. designed the experiments. Y.L. and W.A. did the experiments. A.G., Y.L., and W.A. wrote the article.
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2018, Trends in Food Science and TechnologyCitation Excerpt :Naringenin also modulated the mitochondrial potassium channels, mitochondrial oxidative metabolism activity, estradiol level and estrogen-related pathways (ER and VDR) (Da Pozzo et al., 2017). Besides in cardiac fibroblasts, naringenin improved the cardiac function via upregulating the Nrf2 and/or γ-glutamylcysteine ligase (GCLc) expression-mediated antioxidant effect (Liu, An, & Gao, 2016). Furthermore, naringenin inhibited the cholesterol-induced cardiotoxicity in rats, by altering the relative heart weights (%), cardiac lipid profile (TC, TG, FFA, and phospholipids), serum cardiac markers (CK and LDH), and antioxidant status (CAT, GPx, SOD, GSH, NPSH, Vit C, and Vit E).
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2017, European Journal of PharmacologyCitation Excerpt :We and others have reported that naringin, a narigenin glycone, relieves hyperglycemia-induced cardiac fibrosis and cardiac hypertrophy in diabetic rats (Adebiyi et al., 2016a) and has general cardioprotectic effects under experimental conditions (Cook and Samman, 1996; Mojzisová et al., 2009; Qin et al., 2008). Recently, protective effects of naringenin on cardiorenal syndrome have been reported where it mitigated cardiac remodeling, cardiac dysfunction and left ventricular diastolic pressure in experimental animals (Liu et al., 2016a, 2016b). These actions of naringenin are a consequence of its anti-oxidant effects that activate AMPK-, PPARα–, MAP kinase-mediated signaling pathways (Alam et al., 2014; Adebiyi et al., 2016a).
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