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

• Published in: Archives of toxicology 2011-12, Vol.85 (12), p.1597-1606
• Main Authors: Francescato, Heloísa Della Coletta, Marin, Evelyn Cristina Santana, de Queiroz Cunha, Fernando, Costa, Roberto Silva, da Silva, Cleonice Giovanini Alves, Coimbra, Terezila Machado
• Format: Article
• Language: English
• Subjects: Alkynes - pharmacology; Animals; Antibiotics, Antineoplastic - toxicity; Biomedical and Life Sciences; Biomedicine; Chemotherapy; Doxorubicin - toxicity; Environmental Health; Glutathione - drug effects; Glutathione - metabolism; Glycine - analogs & derivatives; Glycine - pharmacology; Hydrogen Sulfide - metabolism; Inflammation - chemically induced; Kidney - drug effects; Kidney - pathology; Kidney Cortex - drug effects; Kidney Cortex - pathology; Kidneys; Lipid Peroxidation - drug effects; Macrophages - drug effects; Macrophages - metabolism; Male; Neutrophils - drug effects; Neutrophils - metabolism; Occupational Medicine/Industrial Medicine; Organ Toxicity and Mechanisms; Oxidative stress; Oxidative Stress - drug effects; Pharmacology; Pharmacology/Toxicology; Rats; Rats, Wistar; Time Factors; Toxicity
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-011-0717-y

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 (H 2 S) 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 H 2 S 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 H 2 S 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 H 2 S formation and to restriction of oxidative stress and inflammation in the renal cortex.