Limits...
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 expression of RST (a), OAT1 (b), MRP4 (c), and ABCG2 (d) at protein levels in renal cortex of rats. The protein levels were normalized by GAPDH. Values are mean ± SEM of n = 4–6 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


getmorefigures.php?uid=PMC3368504&req=5

fig7: Effects of a 4-week treatment of CdCl2 and coadministration of quercetin on expression of RST (a), OAT1 (b), MRP4 (c), and ABCG2 (d) at protein levels in renal cortex of rats. The protein levels were normalized by GAPDH. Values are mean ± SEM of n = 4–6 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: In order to explore the reasons for renal UA excretion abnormality, we examined the expression levels of renal RST, OAT1, MRP4, and ABCG2 in Cd-exposed rats by RT-PCR and Western blot analyses, respectively. As shown in Figures 6 and 7, Cd exposure significantly increased RST mRNA (3 mg/kg: P < 0.05; 6 mg/kg: P < 0.01) (Figure 6(a)) and protein (3 mg/kg: P < 0.05; 6 mg/kg: P < 0.001) (Figure 7(a)) levels and decreased OAT1 mRNA (3 mg/kg: P < 0.05; 6 mg/kg: P < 0.01) (Figure 6(b)) and protein (6 mg/kg: P < 0.01) levels (Figure 7(b)) in the kidney of rats compared with normal control. Cd exposure suppressed renal mRNA levels of MRP4 (6 mg/kg: P < 0.05) (Figure 6(c)) and ABCG2 (3 and 6 mg/kg: P < 0.001) (Figure 6(d)) and increased renal protein levels of ABCG2 (6 mg/kg: P < 0.05) (Figure 7(d)) in rats. Moreover, 100 mg/kg quercetin ameliorated 3 mg/kg Cd-induced changes of RST mRNA levels (P < 0.05) in rats (Figure 6(a)). Meanwhile, quercetin ameliorated 6 mg/kg Cd-induced changes of RST mRNA levels (50 and 100 mg/kg: P < 0.01) (Figure 6(a)) and protein levels (100 mg/kg: P < 0.05) (Figure 7(a)) in rats. The changed expression levels of renal OAT1 mRNA (100 mg/kg: P < 0.05) and protein (50 and 100 mg/kg: P < 0.05) in 6 mg/kg Cd-exposed rats were also restored by the treatment of quercetin (Figures 6(b) and 7(b)). However, quercetin performed no effects on renal MRP4 and ABCG2 in Cd-exposed rats.


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 expression of RST (a), OAT1 (b), MRP4 (c), and ABCG2 (d) at protein levels in renal cortex of rats. The protein levels were normalized by GAPDH. Values are mean ± SEM of n = 4–6 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

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

fig7: Effects of a 4-week treatment of CdCl2 and coadministration of quercetin on expression of RST (a), OAT1 (b), MRP4 (c), and ABCG2 (d) at protein levels in renal cortex of rats. The protein levels were normalized by GAPDH. Values are mean ± SEM of n = 4–6 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: In order to explore the reasons for renal UA excretion abnormality, we examined the expression levels of renal RST, OAT1, MRP4, and ABCG2 in Cd-exposed rats by RT-PCR and Western blot analyses, respectively. As shown in Figures 6 and 7, Cd exposure significantly increased RST mRNA (3 mg/kg: P < 0.05; 6 mg/kg: P < 0.01) (Figure 6(a)) and protein (3 mg/kg: P < 0.05; 6 mg/kg: P < 0.001) (Figure 7(a)) levels and decreased OAT1 mRNA (3 mg/kg: P < 0.05; 6 mg/kg: P < 0.01) (Figure 6(b)) and protein (6 mg/kg: P < 0.01) levels (Figure 7(b)) in the kidney of rats compared with normal control. Cd exposure suppressed renal mRNA levels of MRP4 (6 mg/kg: P < 0.05) (Figure 6(c)) and ABCG2 (3 and 6 mg/kg: P < 0.001) (Figure 6(d)) and increased renal protein levels of ABCG2 (6 mg/kg: P < 0.05) (Figure 7(d)) in rats. Moreover, 100 mg/kg quercetin ameliorated 3 mg/kg Cd-induced changes of RST mRNA levels (P < 0.05) in rats (Figure 6(a)). Meanwhile, quercetin ameliorated 6 mg/kg Cd-induced changes of RST mRNA levels (50 and 100 mg/kg: P < 0.01) (Figure 6(a)) and protein levels (100 mg/kg: P < 0.05) (Figure 7(a)) in rats. The changed expression levels of renal OAT1 mRNA (100 mg/kg: P < 0.05) and protein (50 and 100 mg/kg: P < 0.05) in 6 mg/kg Cd-exposed rats were also restored by the treatment of quercetin (Figures 6(b) and 7(b)). However, quercetin performed no effects on renal MRP4 and ABCG2 in Cd-exposed rats.

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