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Resveratrol attenuates cisplatin-induced nephrotoxicity in rats

  • Organ Toxicity and Mechanisms
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Abstract

Cisplatin is an antitumor drug widely used in the treatment of many malignant tumors. However, the most common adverse effect, nephrotoxicity, limits the use of this drug in many cancer patients. Resveratrol is a phytoalexin that presents highly efficient protection in experimental nephrotoxicity models. This study evaluated the effect of resveratrol on cisplatin-induced kidney damage. Male Wistar rats were treated with resveratrol (25 mg/kg b.w., i.p.) before the administration of cisplatin (5 mg/kg b.w., i.p.) and killed 2 or 5 days later. Blood and urine samples were collected and the kidneys were removed. Rats from the cisplatin group showed acute tubular cell necrosis and increased immunostaining for ED1 (macrophages/monocytes) and T-lymphocytes in the renal cortex and outer medulla when compared with the control group. These alterations were less intense in animals pre-treated with resveratrol. Moreover, indicators of renal injury such as increased serum creatinine levels, urinary volume and urinary protein caused by the administration of cisplatin, were also significantly reduced with resveratrol. Increased lipid peroxidation and glutathione depletion in tissue were attenuated by resveratrol. In conclusion, resveratrol attenuated the cisplatin-induced structural and functional renal changes by reducing free radicals and inhibiting inflammatory cell infiltrates.

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Fig. 1

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Abbreviations

ATN:

Acute tubular necrosis

cDDP:

Cisplatin

GSH:

Reduced glutathione

MDA:

Malondialdehyde

Res:

Resveratrol

ROS:

Reactive oxygen species

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Acknowledgments

This study was sponsored by the Conselho Nacional de Desenvolvimento Científico e Tecnológico––CNPq. The authors thank Quiral Química do Brasil (Juiz de Fora, Brazil) for their generosity in supplying cisplatin for free. The authors are also grateful to Mrs. Adriana L. G. de Almeida (FMRP-USP) and Mrs. Erica Delloiagono (FMRP-USP) for their technical assistance.

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Authors and Affiliations

  1. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Do Café, s/n, 14041-903, Ribeirao Preto, Brazil

    Cátia Lira Do Amaral, Joana D’arc Castania Darin, Lusânia Maria Greggi Antunes & Maria De Lourdes Pires Bianchi

  2. Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirao Preto, Brazil

    Heloísa Della Coletta Francescato & Terezila Machado Coimbra

  3. Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirao Preto, Brazil

    Roberto Silva Costa

Authors
  1. Cátia Lira Do Amaral
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  2. Heloísa Della Coletta Francescato
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  3. Terezila Machado Coimbra
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  4. Roberto Silva Costa
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  5. Joana D’arc Castania Darin
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  6. Lusânia Maria Greggi Antunes
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  7. Maria De Lourdes Pires Bianchi
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Corresponding author

Correspondence to Lusânia Maria Greggi Antunes.

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Do Amaral, C.L., Francescato, H.D.C., Coimbra, T.M. et al. Resveratrol attenuates cisplatin-induced nephrotoxicity in rats. Arch Toxicol 82, 363–370 (2008). https://doi.org/10.1007/s00204-007-0262-x

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  • DOI: https://doi.org/10.1007/s00204-007-0262-x

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