Pretreatment with quercetin prevents changes in lymphocytes E-NTPDase/E-ADA activities and cytokines secretion in hyperlipidemic rats

Abstract

Hyperlipidemia (HL) is a condition associated with endothelial dysfunction and inflammatory disorders. Purinergic system ectoenzymes play an important role in modulating the inflammatory and immune response. This study investigated whether the preventive treatment with quercetin is able to prevent changes caused by hyperlipidemia in the purinergic system, through the activities of E-NTPDase and E-ADA in lymphocytes, and quantify the nucleotides and nucleoside, and the secretion of anti- and proinflammatory cytokines. Animals were divided into saline/control, saline/quercetin 5 mg/kg, saline/quercetin 25 mg/kg, saline/quercetin 50 mg/kg, saline/simvastatin (0.04 mg/kg), hyperlipidemia, hyperlipidemia/quercetin 5 mg/kg, hyperlipidemia/quercetin 25 mg/kg, hyperlipidemia/quercetin 50 mg/kg, and hyperlipidemia/simvastatin. Animals were pretreated with quercetin for 30 days and hyperlipidemia was subsequently induced by intraperitoneal administration of 500 mg/kg of poloxamer-407. Simvastatin was administered after the induction of hyperlipidemia. Lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Serum was separated for the cytokines and nucleotide/nucleoside quantification. E-NTPDase and E-ADA activities were increased in lymphocytes from hyperlipidemic rats and pretreatment with quercetin was able to prevent the increase in the activities of these enzymes caused by hyperlipidemia. Hyperlipidemic rats when receiving pretreatment with quercetin and treatment with simvastatin showed decreased levels of ATP and ADP when compared to the untreated hyperlipidemic group. The IFN-γ and IL-4 cytokines were increased in the hyperlipidemic group when compared with control group, and decreased when hyperlipidemic rats received the pretreatment with quercetin. However, pretreatment with quercetin was able to prevent the alterations caused by hyperlipidemia probably by regulating the inflammatory process. We can suggest that the quercetin is a promising compound to be used as an adjuvant in the treatment of hyperlipidemia.

Berberine attenuates inflammation and oxidative stress and modulates lymphocyte E‐NTPDase in acute hyperlipidemia

“…The elevation in cytokines was associated with enhanced activities of E‐NTPDase and E‐ADA in lymphocytes. The elevated cytokines and activated E‐NTPDase and E‐ADA in hyperlipidemic rats coincided with previous studies attributed these effects to increased TG, CHO, and LDL‐C (Braun et al, 2018; Klafke et al, 2016; Ruchel et al, 2021). INF‐γ is a pro‐atherogenic cytokine that contributes to inflammatory activities and promotes the adhesion of leukocytes to the endothelium, and studies on atherosclerosis supported the evidence that IL‐4 is pro‐atherogenic (Leon & Zuckerman, 2005; Walch et al, 2006).…”

“…INF‐γ is a pro‐atherogenic cytokine that contributes to inflammatory activities and promotes the adhesion of leukocytes to the endothelium, and studies on atherosclerosis supported the evidence that IL‐4 is pro‐atherogenic (Leon & Zuckerman, 2005; Walch et al, 2006). Both cytokines are increased in P‐407‐induced hyperlipidemia in rodent models (Braun et al, 2018; Ruchel et al, 2021). P‐407‐induced dyslipidemia has been associated with upregulated TNF‐α, IL‐6, and IL‐1β, not only in the blood as reported by Saja et al (2018), but also in different tissues, including hippocampus (Park et al, 2021).…”

Role of purinergic signalling in obesity-associated end-organ damage: focus on the effects of natural plant extracts

“…EADA converts adenosine into inosine, regulating adenosine receptor engagement ( 8 ). Pretreatment with quercetin was indicated to suppress the ENTPDase and EADA activities and reduce the serum ATP and ADP levels, therefore suppressing of inflammatory cell responses and atherosclerosis ( 45 ).…”

“…Polyphenols, such as quercetin and resveratrol, have been studied for their potential to prevent and alleviate obesity-related metabolic diseases ( 45 ). These molecules are available in the form of capsules or pills and can be taken as dietary supplements.…”

Rutin and Quercetin Decrease Cholesterol in HepG2 Cells but Not Plasma Cholesterol in Hamsters by Oral Administration

“…As with R, Q is also widely present in many foods, such as buckwheat, apple, onion, red wine, and cranberry [ 16 , 17 , 18 ]. Q has also been demonstrated to possess anti-oxidative, anti-viral, anti-atherosclerotic, and anti-inflammatory activities [ 19 , 20 , 21 , 22 , 23 ]. Various studies have been carried out to investigate the effects of R and Q on cholesterol metabolism using different models, including vascular endothelial cells, intestinal epithelial cells, macrophages, hepatic cells, male Swiss ablino mice, male Wistar rats, male Sprague Dawley rats, male New Zealand white rabbits, male C576J/BL mice, and male golden Syrian hamsters [ 24 , 25 , 26 , 27 ].…”