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Quercetin Protects against Cadmium-Induced Renal Uric Acid Transport System Alteration and Lipid Metabolism Disorder in Rats.

Wang J, Pan Y, Hong Y, Zhang QY, Wang XN, Kong LD - Evid Based Complement Alternat Med (2012)

Bottom Line: The aim of this study was to determine the effect of quercetin, a dietary flavonoid with anti-hyperuricemic and anti-dyslipidemic properties, on the alteration of renal UA transport system and disorder of renal lipid accumulation in 3 and 6 mg/kg Cd-exposed rats for 4 weeks.We had proved that Cd-induced disorder of renal UA transport and production system might have cross-talking with renal AMPK-PPARα/PGC-1β signal pathway impairment, contributing to Cd nephrotoxicity of rats.Quercetin was found to be effective against Cd-induced dysexpression of RST and OAT1 with XOR hyperactivity and impairment of AMPK-PPARα/PGC-1β signal pathway, resulting in renal lipid accumulation reduction of rats.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.

ABSTRACT
Hyperuricemia and dyslipidemia are involved in Cd nephrotoxicity. The aim of this study was to determine the effect of quercetin, a dietary flavonoid with anti-hyperuricemic and anti-dyslipidemic properties, on the alteration of renal UA transport system and disorder of renal lipid accumulation in 3 and 6 mg/kg Cd-exposed rats for 4 weeks. Cd exposure induced hyperuricemia with renal XOR hyperactivity and UA excretion dysfunction in rats. Simultaneously, abnormal expression levels of renal UA transport-related proteins including RST, OAT1, MRP4 and ABCG2 were observed in Cd-exposed rats with inhibitory activity of renal Na(+)-K(+)-ATPase. Furthermore, Cd exposure disturbed lipid metabolism with down-regulation of AMPK and its downstream targets PPARα, OCTN2 and CPT1 expressions, and up-regulation of PGC-1β and SREBP-1 expressions in renal cortex of rats. We had proved that Cd-induced disorder of renal UA transport and production system might have cross-talking with renal AMPK-PPARα/PGC-1β signal pathway impairment, contributing to Cd nephrotoxicity of rats. Quercetin was found to be effective against Cd-induced dysexpression of RST and OAT1 with XOR hyperactivity and impairment of AMPK-PPARα/PGC-1β signal pathway, resulting in renal lipid accumulation reduction of rats.

No MeSH data available.


Related in: MedlinePlus

Effects of a 4-week treatment of CdCl2 and coadministration of quercetin on TG levels in serum (a) and kidney (b); VLDL levels in serum (c) and kidney (d) in rats. Values are mean ± SEM of n = 8 in each group. P value CdCl2 versus control at  ++<0.01 and +++<0.001; treatment versus CdCl2 at *<0.05, **<0.01, and ***<0.001 for LSD post hoc test.
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fig8: Effects of a 4-week treatment of CdCl2 and coadministration of quercetin on TG levels in serum (a) and kidney (b); VLDL levels in serum (c) and kidney (d) in rats. Values are mean ± SEM of n = 8 in each group. P value CdCl2 versus control at ++<0.01 and +++<0.001; treatment versus CdCl2 at *<0.05, **<0.01, and ***<0.001 for LSD post hoc test.

Mentions: UA and XOR are confirmed to be related to lipid metabolism [13], we addressed the question whether Cd nephrotoxicity was correlated to renal lipid metabolism disorder. Thus, TG and VLDL levels were detected in Cd-exposed rats. Cd exposure increased TG levels in serum (6 mg/kg: P < 0.001) and kidney (3 and 6 mg/kg: P < 0.001) of rats compared with normal control (Figures 8(a) and 8(b)), exhibiting renal lipid accumulation. 100 mg/kg quercetin significantly reduced serum TG levels (P < 0.05) in 6 mg/kg Cd-exposed rats (Figure 8(a)). The increased renal TG levels were ameliorated by the treatment of quercetin at 50 mg/kg (P < 0.05) and 100 mg/kg (P < 0.01) in 3 and 6 mg/kg Cd-exposed rats (Figure 8(b)). However, Cd exposure did not significantly change serum and renal VLDL levels (Figures 8(c) and 8(d)). 100 mg/kg quercetin reduced renal VLDL levels (P < 0.01) in 6 mg/kg Cd-exposed rats (Figure 8(d)).


Quercetin Protects against Cadmium-Induced Renal Uric Acid Transport System Alteration and Lipid Metabolism Disorder in Rats.

Wang J, Pan Y, Hong Y, Zhang QY, Wang XN, Kong LD - Evid Based Complement Alternat Med (2012)

Effects of a 4-week treatment of CdCl2 and coadministration of quercetin on TG levels in serum (a) and kidney (b); VLDL levels in serum (c) and kidney (d) in rats. Values are mean ± SEM of n = 8 in each group. P value CdCl2 versus control at  ++<0.01 and +++<0.001; treatment versus CdCl2 at *<0.05, **<0.01, and ***<0.001 for LSD post hoc test.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368504&req=5

fig8: Effects of a 4-week treatment of CdCl2 and coadministration of quercetin on TG levels in serum (a) and kidney (b); VLDL levels in serum (c) and kidney (d) in rats. Values are mean ± SEM of n = 8 in each group. P value CdCl2 versus control at ++<0.01 and +++<0.001; treatment versus CdCl2 at *<0.05, **<0.01, and ***<0.001 for LSD post hoc test.
Mentions: UA and XOR are confirmed to be related to lipid metabolism [13], we addressed the question whether Cd nephrotoxicity was correlated to renal lipid metabolism disorder. Thus, TG and VLDL levels were detected in Cd-exposed rats. Cd exposure increased TG levels in serum (6 mg/kg: P < 0.001) and kidney (3 and 6 mg/kg: P < 0.001) of rats compared with normal control (Figures 8(a) and 8(b)), exhibiting renal lipid accumulation. 100 mg/kg quercetin significantly reduced serum TG levels (P < 0.05) in 6 mg/kg Cd-exposed rats (Figure 8(a)). The increased renal TG levels were ameliorated by the treatment of quercetin at 50 mg/kg (P < 0.05) and 100 mg/kg (P < 0.01) in 3 and 6 mg/kg Cd-exposed rats (Figure 8(b)). However, Cd exposure did not significantly change serum and renal VLDL levels (Figures 8(c) and 8(d)). 100 mg/kg quercetin reduced renal VLDL levels (P < 0.01) in 6 mg/kg Cd-exposed rats (Figure 8(d)).

Bottom Line: The aim of this study was to determine the effect of quercetin, a dietary flavonoid with anti-hyperuricemic and anti-dyslipidemic properties, on the alteration of renal UA transport system and disorder of renal lipid accumulation in 3 and 6 mg/kg Cd-exposed rats for 4 weeks.We had proved that Cd-induced disorder of renal UA transport and production system might have cross-talking with renal AMPK-PPARα/PGC-1β signal pathway impairment, contributing to Cd nephrotoxicity of rats.Quercetin was found to be effective against Cd-induced dysexpression of RST and OAT1 with XOR hyperactivity and impairment of AMPK-PPARα/PGC-1β signal pathway, resulting in renal lipid accumulation reduction of rats.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.

ABSTRACT
Hyperuricemia and dyslipidemia are involved in Cd nephrotoxicity. The aim of this study was to determine the effect of quercetin, a dietary flavonoid with anti-hyperuricemic and anti-dyslipidemic properties, on the alteration of renal UA transport system and disorder of renal lipid accumulation in 3 and 6 mg/kg Cd-exposed rats for 4 weeks. Cd exposure induced hyperuricemia with renal XOR hyperactivity and UA excretion dysfunction in rats. Simultaneously, abnormal expression levels of renal UA transport-related proteins including RST, OAT1, MRP4 and ABCG2 were observed in Cd-exposed rats with inhibitory activity of renal Na(+)-K(+)-ATPase. Furthermore, Cd exposure disturbed lipid metabolism with down-regulation of AMPK and its downstream targets PPARα, OCTN2 and CPT1 expressions, and up-regulation of PGC-1β and SREBP-1 expressions in renal cortex of rats. We had proved that Cd-induced disorder of renal UA transport and production system might have cross-talking with renal AMPK-PPARα/PGC-1β signal pathway impairment, contributing to Cd nephrotoxicity of rats. Quercetin was found to be effective against Cd-induced dysexpression of RST and OAT1 with XOR hyperactivity and impairment of AMPK-PPARα/PGC-1β signal pathway, resulting in renal lipid accumulation reduction of rats.

No MeSH data available.


Related in: MedlinePlus