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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 weekly urine UA levels (a), levels of serum UA (b), and urine UMOD (c) at the end of week 4. Values are mean ± SEM of n = 8 in each group. P value CdCl2 versus control at +<0.05, ++<0.01, +++<0.001; treatment versus CdCl2 at *<0.05 and **<0.01 for LSD post hoc test.
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fig2: Effects of a 4-week treatment of CdCl2 and coadministration of quercetin on weekly urine UA levels (a), levels of serum UA (b), and urine UMOD (c) at the end of week 4. Values are mean ± SEM of n = 8 in each group. P value CdCl2 versus control at +<0.05, ++<0.01, +++<0.001; treatment versus CdCl2 at *<0.05 and **<0.01 for LSD post hoc test.

Mentions: UA is a biomarker of nephropathy, and its detection is stable and easy. Compared with control group, urine UA levels were increased in rats exposed to Cd from week 2 and maintained until week 4 (3 mg/kg Cd: week 2, P < 0.01, week 3, P < 0.05, and week 4, P < 0.05; 6 mg/kg Cd: week 2, P < 0.01, week 3, P < 0.001, and week 4, P < 0.001) (Figure 2(a)). The decreased urine UA levels were observed in 6 mg/kg Cd-exposed rats receiving quercetin at week 4 (quercetin 50 mg/kg: P < 0.05; 100 mg/kg: P < 0.01). Furthermore, 6 mg/kg Cd exposure increased serum UA levels in rats compared with normal control (P < 0.001), which were significantly restored by the treatment of quercetin (P < 0.05) (Figure 2(b)). UMOD is a useful marker of renal dysfunction associated with hyperuricemia. The decreased urine UMOD levels (P < 0.05) were observed in 6 mg/kg Cd-exposed rats. Quercetin did not affect urine UMOD levels in Cd-exposed rats (Figure 2(c)).


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 weekly urine UA levels (a), levels of serum UA (b), and urine UMOD (c) at the end of week 4. Values are mean ± SEM of n = 8 in each group. P value CdCl2 versus control at +<0.05, ++<0.01, +++<0.001; treatment versus CdCl2 at *<0.05 and **<0.01 for LSD post hoc test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368504&req=5

fig2: Effects of a 4-week treatment of CdCl2 and coadministration of quercetin on weekly urine UA levels (a), levels of serum UA (b), and urine UMOD (c) at the end of week 4. Values are mean ± SEM of n = 8 in each group. P value CdCl2 versus control at +<0.05, ++<0.01, +++<0.001; treatment versus CdCl2 at *<0.05 and **<0.01 for LSD post hoc test.
Mentions: UA is a biomarker of nephropathy, and its detection is stable and easy. Compared with control group, urine UA levels were increased in rats exposed to Cd from week 2 and maintained until week 4 (3 mg/kg Cd: week 2, P < 0.01, week 3, P < 0.05, and week 4, P < 0.05; 6 mg/kg Cd: week 2, P < 0.01, week 3, P < 0.001, and week 4, P < 0.001) (Figure 2(a)). The decreased urine UA levels were observed in 6 mg/kg Cd-exposed rats receiving quercetin at week 4 (quercetin 50 mg/kg: P < 0.05; 100 mg/kg: P < 0.01). Furthermore, 6 mg/kg Cd exposure increased serum UA levels in rats compared with normal control (P < 0.001), which were significantly restored by the treatment of quercetin (P < 0.05) (Figure 2(b)). UMOD is a useful marker of renal dysfunction associated with hyperuricemia. The decreased urine UMOD levels (P < 0.05) were observed in 6 mg/kg Cd-exposed rats. Quercetin did not affect urine UMOD levels in Cd-exposed rats (Figure 2(c)).

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