Protective effects of quercetin on cadmium-induced cytotoxicity in primary cultures of rat proximal tubular cells.

OBJECTIVE To investigate the protective effects of quercetin on cadmium-induced cytotoxicity in primary cultures of rat proximal tubular (rPT) cells. METHODS Primary cultures of rPT cells undergoing exponential growth were incubated with 1.0 μg/mL quercetin and/or cadmium (2.5, 5.0 μmol/L), in a serum-free medium at 37 °C at different time intervals. Commercial kits were used and flow cytometric analyses were performed on rPT cell cultures to assay apoptosis and oxidative stress. RESULTS Exposure of rPT cells to cadmium acetate (2.5, 5.0 µmol/L) induced a decrease in cell viability, caused an increase in apoptotic rate and apoptotic morphological changes. Simultaneously, elevation of intracellular reactive oxygen species, malondialdehyde and calcium levels, depletion of mitochondrial membrane potential and intracellular glutathione, and inhibition of Na+, K+-ATPase, Ca2+-ATPase, glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activities were revealed during the cadmium exposure of rPT cells. However, simultaneous supplementation with 1 µg/mL quercetin protected rPT cells against cadmium-induced cytotoxicity through inhibiting apoptosis, attenuating lipid peroxidation, renewing mitochondrial function and elevating the intracellular antioxidants (non-enzymatic and enzymic) levels. CONCLUSION The present study has suggested that quercetin, as a widely distributed dietary antioxidant, contributes potentially to prevent cadmium-induced cytotoxicity in rPT cells.

[1]  Y. Mi,et al.  Quercetin attenuates cadmium-induced oxidative damage and apoptosis in granulosa cells from chicken ovarian follicles. , 2011, Reproductive toxicology.

[2]  S. Prabu,et al.  Quercetin protects against oxidative stress-related renal dysfunction by cadmium in rats. , 2010, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[3]  C. Sánchez-Moreno,et al.  Flavonoid–flavonoid interaction and its effect on their antioxidant activity , 2010 .

[4]  Dong-Mei Wu,et al.  Quercetin protects rat liver against lead-induced oxidative stress and apoptosis. , 2010, Environmental toxicology and pharmacology.

[5]  Zongping Liu,et al.  Effects of Lead and/or Cadmium on the Oxidative Damage of Rat Kidney Cortex Mitochondria , 2010, Biological Trace Element Research.

[6]  F. Thévenod Cadmium and cellular signaling cascades: to be or not to be? , 2009, Toxicology and applied pharmacology.

[7]  Zongping Liu,et al.  Oxidative stress and apoptotic changes in primary cultures of rat proximal tubular cells exposed to lead , 2009, Archives of Toxicology.

[8]  E. M. Reyes-Reyes,et al.  Environmental toxicity, oxidative stress and apoptosis: ménage à trois. , 2009, Mutation research.

[9]  Ying-Na Li,et al.  The dysfunction of ATPases due to impaired mitochondrial respiration in phosgene-induced pulmonary edema. , 2008, Biochemical and biophysical research communications.

[10]  Xuezhong Liu,et al.  Role of Oxidative Stress, Apoptosis, and Intracellular Homeostasis in Primary Cultures of Rat Proximal Tubular Cells Exposed to Cadmium , 2008, Biological Trace Element Research.

[11]  Yan Liu,et al.  Cytoprotective effects of selenium on cadmium-induced LLC-PK1 cells apoptosis by activating JNK pathway. , 2007, Toxicology in vitro : an international journal published in association with BIBRA.

[12]  Sten Orrenius,et al.  Mitochondria, oxidative stress and cell death , 2007, Apoptosis.

[13]  L. Pari,et al.  Cytoprotective and antioxidant role of diallyl tetrasulfide on cadmium induced renal injury: an in vivo and in vitro study. , 2007, Life sciences.

[14]  A. Wach,et al.  Quercetin content in some food and herbal samples , 2007 .

[15]  M. Arévalo,et al.  Protective effect of quercetin on experimental chronic cadmium nephrotoxicity in rats is based on its antioxidant properties. , 2006, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[16]  N. Sen,et al.  Lipid peroxidation associated cardiolipin loss and membrane depolarization in rat brain mitochondria , 2006, Neurochemistry International.

[17]  Dennis A. Turner,et al.  Optical and pharmacological tools to investigate the role of mitochondria during oxidative stress and neurodegeneration , 2006, Progress in Neurobiology.

[18]  M. Oset-Gasque,et al.  Cadmium induces reactive oxygen species generation and lipid peroxidation in cortical neurons in culture. , 2006, Free radical biology & medicine.

[19]  J. López-Novoa,et al.  Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats. , 2006, Toxicology and applied pharmacology.

[20]  E. Oruç,et al.  Oxidative stress-related and ATPase effects of etoxazole in different tissues of Oreochromisniloticus. , 2005, Environmental toxicology and pharmacology.

[21]  C. Sheline,et al.  Apoptotic insults impair Na+, K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress. , 2003, Journal of cell science.

[22]  Y. Oyama,et al.  Tri-n-butyltin-induced change in cellular level of glutathione in rat thymocytes: a flow cytometric study. , 2000, Toxicology letters.

[23]  S. Chakraborti,et al.  Oxidant, mitochondria and calcium: an overview. , 1999, Cellular signalling.

[24]  N. Sato,et al.  Senescence marker protein-30 (SMP30) rescues cell death by enhancing plasma membrane Ca(2+)-pumping activity in Hep G2 cells. , 1998, Biochemical and biophysical research communications.

[25]  Y. Oyama,et al.  Fluorescent estimation of H2O2-induced changes in cell viability and cellular nonprotein thiol level of dissociated rat thymocytes. , 1996, Japanese journal of pharmacology.

[26]  C Haanen,et al.  A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. , 1995, Journal of immunological methods.

[27]  K. Tsuchiya,et al.  Estimation of variation among individuals of biological half-time of cadmium calculated from accumulation data. , 1995, Environmental research.

[28]  S. Dauwe,et al.  Stage- and segment-specific expression of cell-adhesion molecules N-CAM, A-CAM, and L-CAM in the kidney. , 1993, Kidney international.

[29]  R. Goyer,et al.  Mechanisms of lead and cadmium nephrotoxicity. , 1989, Toxicology letters.

[30]  S. Marklund,et al.  Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. , 1974, European journal of biochemistry.

[31]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.