ABC | Volume 115, Nº1, July 2020

Original Article Derakhshanian et al. Quercetin improves glucocorticoid-induced dyslipidemia Arq Bras Cardiol. 2020; 115(1):102-108 for TG concentrations, which decreased to the control level as a result of high dose quercetin administration. Methylprednisolone also caused a moderate increase in HDL levels, which was not significantly changed following quercetin supplementation. Although the hyperlipidemic impact of GCs has been noticed for the last decades, the molecular mechanisms are not well recognized yet. Some in vitro and in vivo studies demonstrated that these anti-inflammatory drugs can directly increase hepatic HDL production, up-regulate lipoprotein lipase activity and impair LDL catabolism by reducing hepatic LDL receptors expression and activity. 15,20 Consequently, they contribute to fatty liver development by increasing fatty acid synthesis and decreasing β oxidation. 21 On the other hand, flavonoids have been described as lipid metabolism modulators. They mostly act through the inhibition of phosphodiesterase, alteration of hepatic cholesterol absorption and triglyceride production and secretion. 22-25 In addition, quercetin as a potent antioxidant distributed in both the lipid bilayer and aqueous phase of the cell, can suppress lipid peroxidation by radical scavenging activity. 26 Large studies have shown that ApoB/Al ratio is superior to the total cholesterol and TG for cardiovascular risk prediction in both genders and at all age ranges. 27 Given that the ApoB/Al ratio is a measurement of the number of ApoB atherogenic particles over the number of ApoAl anti-atherogenic particles, there is also a possibility that it is a more important factor than the amount of lipids carried per particle. In the present study, quercetin intake significantly decreased ApoB/AI ratio, which might be an important indicator of lower cardiovascular risk in the future. 27,28 At the end of intervention, all glucocorticoid-treated animals showed a significant weight reduction compared to their controls, which might be due to glucocorticoid- induced anorexia in rats, which has been previously reported, 29 or to severe proteolysis and muscle loss. 30 One of the limitations of this study was the lack of precise data about the animals’ food intake, which could be very useful for the interpretation of GC-induced weight loss in rats. Overall, our findings are in accordance with previous studies reporting the beneficial effects of flavonoids on lipid metabolism. 31 This is the first research evaluating the impact of quercetin on GC-induced hyperlipidemia. However, the hypolipidemic effect of some other flavonoids has been reported in GC-treated rats. 32 Other favorable properties of quercetin in improving bone density and modifying blood glucose, make this flavonoid an excellent choice to control glucocorticoid side effects. 33 Conclusion Quercetin administration, at both doses of 50 and 150 mg/kg, was able to reverse the untoward effects of high-dose glucocorticoids on the lipid profile of rats, and might be considered for combination therapy with GCs to minimize the resulting dyslipidemia. Table 1 – Initial and final body weight (gram) of experimental groups Body weight Control MP MP+Q50 MP+Q150 Initial 212±29 212±27 210±28 212±28 Final 214±30 † 182±22 *,‡ 185±20 *,‡ 180±16 *,‡ Data are presented as Mean±SD. N=8 for all groups. MP, methylprednisolone; Q50, quercetin 50 mg/kg; Q150, quercetin 150 mg/kg; Analysis of variance (ANOVA) followed by Bonferroni test. * p<0.05 compared with control group, † p<0.05 compared with MP group, ‡ p<0.05 compared with the initial weight of same group. Table 2 – Lipid profile of experimental groups after six weeks of intervention Control MP MP+Q50 MP+Q150 p value TC (mg/dl) 89.12±3.35 193.50±12.77 *.‡ 108.75±15.47 *.† 105.87±11.25 *.† <0.001 HDL (mg/dl) 34.25±3.69 41.37±5.75 * 38.25±4.77 39.00±4.07 =0.03 LDL (mg/dl) 41.87±3.79 119.22±12.70 *.‡ 52.72±15.15 † 52.22±10.87 † <0.001 TG (mg/dl) 65.00±4.34 164.50±9.36 *.‡ 88.87±12.93 *.† 73.25±11.33 †.‡ <0.001 TC/HDL 2.62±0.27 4.76±0.86 *.‡ 2.86±0.42 † 2.74±0.47 †.‡ <0.001 TG/HDL 1.92±0.29 4.05±0.71 *.‡ 2.33±0.34 † 1.92±0.51 † <0.001 LDL/HDL 1.24±0.23 2.95±0.73 *.‡ 1.39±0.43 † 1.36±0.38 † <0.001 Apo B/ Al 0.93±0.16 1.63±0.19 *.‡ 1.25±0.30 † 1.06±0.28 † <0.001 Data are presented as Mean±SD. n=8 for all groups. MP: methylprednisolone; Q50: quercetin 50 mg/kg; Q150: quercetin 150 mg/kg; TC: total cholesterol; TG: triglyceride; HDL: high-density lipoprotein; LDL: low-density lipoprotein; ApoB/Al: apolipoprotein B to apolipoprotein Al ratio; Analysis of variance (ANOVA) followed by Bonferroni test. * p<0.05 compared with control group, † p<0.05 compared with MP group, ‡ p<0.05 compared with MP+Q50. 104