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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 urinary activity of NAG (a), levels of Cr (b), RBP (c), β2-MG (d), and ALB (e) in rats. Values are mean ± SEM of n = 8 in each group. P value CdCl2 versus control at +<0.05, ++<0.01, and +++<0.001; treatment versus CdCl2 at *<0.05 and **<0.01 for LSD post hoc test.
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fig1: Effects of a 4-week treatment of CdCl2 and coadministration of quercetin on urinary activity of NAG (a), levels of Cr (b), RBP (c), β2-MG (d), and ALB (e) in rats. Values are mean ± SEM of n = 8 in each group. P value CdCl2 versus control at +<0.05, ++<0.01, and +++<0.001; treatment versus CdCl2 at *<0.05 and **<0.01 for LSD post hoc test.

Mentions: Dysfunction and damage of renal tubules are characterized by the increased activity of urine NAG/Cr [23]. Figure 1(a) showed that Cd at 3 mg/kg (P < 0.01) and 6 mg/kg (P < 0.001) increased urine NAG activity in rats. Quercetin at 50 and 100 mg/kg significantly inhibited NAG activity (P < 0.05) in 3 mg/kg Cd-exposed rats, the latter decreased NAG activity (P < 0.01) in 6 mg/kg Cd-exposed rats. In addition, there were no significant changes of Cr levels in serum (data not shown) and urine (Figure 1(b)) among the tested groups.


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 urinary activity of NAG (a), levels of Cr (b), RBP (c), β2-MG (d), and ALB (e) in rats. Values are mean ± SEM of n = 8 in each group. P value CdCl2 versus control at +<0.05, ++<0.01, and +++<0.001; treatment versus CdCl2 at *<0.05 and **<0.01 for LSD post hoc test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Effects of a 4-week treatment of CdCl2 and coadministration of quercetin on urinary activity of NAG (a), levels of Cr (b), RBP (c), β2-MG (d), and ALB (e) in rats. Values are mean ± SEM of n = 8 in each group. P value CdCl2 versus control at +<0.05, ++<0.01, and +++<0.001; treatment versus CdCl2 at *<0.05 and **<0.01 for LSD post hoc test.
Mentions: Dysfunction and damage of renal tubules are characterized by the increased activity of urine NAG/Cr [23]. Figure 1(a) showed that Cd at 3 mg/kg (P < 0.01) and 6 mg/kg (P < 0.001) increased urine NAG activity in rats. Quercetin at 50 and 100 mg/kg significantly inhibited NAG activity (P < 0.05) in 3 mg/kg Cd-exposed rats, the latter decreased NAG activity (P < 0.01) in 6 mg/kg Cd-exposed rats. In addition, there were no significant changes of Cr levels in serum (data not shown) and urine (Figure 1(b)) among the tested groups.

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