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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 expression of OCTN2 (a), CPT1 (b), AMPK (c), PPARα (d), SREBP-1 (e), PGC-1β (f) at mRNA levels, and OCTN2 (g) and CPT1 (h) at protein levels in renal cortex of rats. The mRNA levels or protein levels were normalized by GAPDH, respectively. Values are mean ± SEM of n = 4–6 in each group. P value CdCl2 versus control at + < 0.05, ++ < 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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fig9: Effects of a 4-week treatment of CdCl2 and coadministration of quercetin on expression of OCTN2 (a), CPT1 (b), AMPK (c), PPARα (d), SREBP-1 (e), PGC-1β (f) at mRNA levels, and OCTN2 (g) and CPT1 (h) at protein levels in renal cortex of rats. The mRNA levels or protein levels were normalized by GAPDH, respectively. Values are mean ± SEM of n = 4–6 in each group. P value CdCl2 versus control at + < 0.05, ++ < 0.01, and +++<0.001; treatment versus CdCl2 at *<0.05, **<0.01, and ***<0.001 for LSD post hoc test.

Mentions: L-carnitine is essential to fatty acid β-oxidation from mitochondrial membrane mediated by CPT1. OCTN2 is an important transporter for L-carnitine reabsorption [29]. However, no significant changes of L-carnitine levels in serum, urine, and kidney cortex were observed in the tested groups (data not shown). Cd exposure reduced renal levels of OCTN2 and CPT1 mRNA (3 mg/kg: P < 0.05; 6 mg/kg: P < 0.001) (Figures 9(a) and 9(b)) and protein (P < 0.001) (Figures 9(g) and 9(h)) in rats compared with normal control. These data indicated that Cd-induced OCTN2 downregulation did not affect L-carnitine levels, which might not be an important factor to cause renal lipid metabolism disorder in Cd nephrotoxicity of 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 OCTN2 (a), CPT1 (b), AMPK (c), PPARα (d), SREBP-1 (e), PGC-1β (f) at mRNA levels, and OCTN2 (g) and CPT1 (h) at protein levels in renal cortex of rats. The mRNA levels or protein levels were normalized by GAPDH, respectively. Values are mean ± SEM of n = 4–6 in each group. P value CdCl2 versus control at + < 0.05, ++ < 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

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getmorefigures.php?uid=PMC3368504&req=5

fig9: Effects of a 4-week treatment of CdCl2 and coadministration of quercetin on expression of OCTN2 (a), CPT1 (b), AMPK (c), PPARα (d), SREBP-1 (e), PGC-1β (f) at mRNA levels, and OCTN2 (g) and CPT1 (h) at protein levels in renal cortex of rats. The mRNA levels or protein levels were normalized by GAPDH, respectively. Values are mean ± SEM of n = 4–6 in each group. P value CdCl2 versus control at + < 0.05, ++ < 0.01, and +++<0.001; treatment versus CdCl2 at *<0.05, **<0.01, and ***<0.001 for LSD post hoc test.
Mentions: L-carnitine is essential to fatty acid β-oxidation from mitochondrial membrane mediated by CPT1. OCTN2 is an important transporter for L-carnitine reabsorption [29]. However, no significant changes of L-carnitine levels in serum, urine, and kidney cortex were observed in the tested groups (data not shown). Cd exposure reduced renal levels of OCTN2 and CPT1 mRNA (3 mg/kg: P < 0.05; 6 mg/kg: P < 0.001) (Figures 9(a) and 9(b)) and protein (P < 0.001) (Figures 9(g) and 9(h)) in rats compared with normal control. These data indicated that Cd-induced OCTN2 downregulation did not affect L-carnitine levels, which might not be an important factor to cause renal lipid metabolism disorder in Cd nephrotoxicity of 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