Protective role of quercetin against lead-induced inflammatory response in rat kidney through the ROS-mediated MAPKs and NF-κB pathway.
ABSTRACT Lead (Pb) exposure is considered as a risk factor for the development of renal dysfunction. The flavonoid quercetin (QE) in diets exerts the nephroprotective effects. This study investigated the effects of quercetin on renal oxidative stress and inflammation in rats exposed to Pb.
Wistar rats were divided into normal, lead exposure groups, lead plus quercetin groups and quercetin groups. Rats were exposed to lead acetate in the drinking water (500mgPb/L) with or without quercetin co-administration (25 and 50mgQU/kg intragastrically once daily). After 75days, serum uric acid, urea, creatinine, renal reactive oxygen species (ROS) production, thiobarbituric acid reactive substances (TBARS) and histopathological analysis were performed. Pb content in kidney was also assayed. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), the extracellular-receptor kinases (ERK1/2), the c-Jun N-terminal kinases (JNK1/2), p38 MAPK and nuclear factor-κB (NF-κB) were measured.
Quercetin significantly prevented Pb-induced nephrotoxicity in a dose-dependent manner, indicated by both diagnostic indicators and histopathological analysis. Quercetin significantly decreased Pb content in kidney. Pb-induced profound elevations of oxidative stress in kidney were suppressed by quercetin. Furthermore, quercetin significantly inhibited Pb-induced inflammation in rat kidney.
These results suggest that quercetin has the nephroprotective actions. The inhibition of Pb-induced kidney inflammation by quercetin is due at least in part to its anti-oxidant activity and its ability to modulate the MAPK and NF-κB signaling pathway.
Quercetin might be a potent nephroprotective drug to protect Pb-induced kidney injury.
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ABSTRACT: Quercetin is a well-known antioxidant. Here, we investigated the effects of treatment with quercetin on mean arterial pressure (MAP), heart rate (HR) and baroreflex sensitivity (BRS) in spontaneously hypertensive rats (SHR). SHR and their controls (WKY) were orally treated with quercetin (2, 10 or 25 mg/kg/day) or saline for seven days. On the 8th day, MAP and HR were recorded. BRS was tested using phenylephrine (8 mg/kg, i.v.) and sodium nitroprusside (25 mg/kg, i.v.). Oxidative stress was measured by tiobarbituric acid reactive species assay. The doses of 10 (n = 8) and 25 mg/kg (n = 8) were able to decrease the MAP in SHR (n = 9) (163 ± 4 and 156 ± 5 vs. 173 ± 6, respectively, p < 0.05) but not in WKY (117 ± 1 and 118 ± 2 vs. 113 ± 1, respectively, p < 0.05). The dose of 25 mg/kg/day increased the sensitivity of parasympathetic component of the baroreflex (−2.47 ± 0.31 vs. −1.25 ± 0.8 bpm/mmHg) and decreased serum oxidative stress in SHR (2.04 ± 0.17 vs. 3.22 ± 0.37 nmol/mL, n = 6). Our data suggest that treatment with quercetin reduces hypertension and improves BRS in SHR via reduction in oxidative stress.Molecules 01/2012; 17(11):12997-3008. · 2.39 Impact Factor