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Role of endogenous hydrogen sulfide on renal damage induced by adriamycin injection

  • Organ Toxicity and Mechanisms
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Abstract

A single injection of adriamycin (ADR) induces marked and persistent proteinuria in rats that progress to glomerular and tubulointerstitial lesions. It has been shown that ADR-induced nephrotoxicity is mediated, at least in part, by oxidative stress that lead to inflammation. Endogenous hydrogen sulfide (H2S) is synthesized from l-cysteine and is an important signaling molecule in inflammation. This study evaluates the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the evolution of renal damage induced by ADR. The rats were injected i.p. with 0.15 M NaCl or PAG (50 mg/kg) 2 h after ADR injection (3.5 mg/kg). Control rats were injected with 0.15 M NaCl or PAG only. Twenty hours urine samples were collected for albuminuria and creatinine measurements on days 1 and 14 after saline or ADR injections and on days 2 and 15 blood samples were collected to measure plasma creatinine, then the rats were killed. The kidneys were removed for H2S formation evaluation, renal lipid peroxidation and glutathione levels, and histological and immunohistochemical analysis. On day 2 after ADR injection the rats presented increase in oxidative stress associated with neutrophils and macrophages influx in renal tissue. On day 15 the rats also presented increased desmin expression at glomerular edge and vimentin in cortical tubulointerstitium, as well as albuminuria. All these alterations were reduced by PAG injection. The protective effect of PAG on ADR nephrotoxicity was associated to decreased H2S formation and to restriction of oxidative stress and inflammation in the renal cortex.

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Acknowledgments

The authors are grateful to Rubens Fernando de Melo, Giuliana Bertozi Francisco, and Flávio Henrique Leite, for their technical assistance. Dr. Heloísa D. C. Francescato, Dr. Roberto Silva Costa and Dr. Terezila Machado Coimbra are recipients of Conselho Nacional de Desenvolvimento Científico e Tecnológico, DF, Brazil, fellowship. This study was presented in part at the 42nd Annual Renal Week Meeting held in San Diego, California, in November of 2009.

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The authors declare that they have no Conflict of interest.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil

    Heloísa Della Coletta Francescato, Evelyn Cristina Santana Marin, Cleonice Giovanini Alves da Silva & Terezila Machado Coimbra

  2. Department of Pharmacology, Faculty of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil

    Fernando de Queiroz Cunha

  3. Department of Pathology, Faculty of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil

    Roberto Silva Costa

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  1. Heloísa Della Coletta Francescato
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  5. Cleonice Giovanini Alves da Silva
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Correspondence to Terezila Machado Coimbra.

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Francescato, H.D.C., Marin, E.C.S., de Queiroz Cunha, F. et al. Role of endogenous hydrogen sulfide on renal damage induced by adriamycin injection. Arch Toxicol 85, 1597–1606 (2011). https://doi.org/10.1007/s00204-011-0717-y

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