Inhibition of hydrogen sulphide formation reduces cisplatin-induced renal damage

Abstract

Background. Cisplatin (CP)-induced renal damage is associated with inflammation. Hydrogen sulphide (H(2)S) is involved in models of inflammation. This study evaluates the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H(2)S formation, on the renal damage induced by CP.Methods. the rats were injected with CP (5 mg/kg, i.p.) or PAG(5 mg/kg twice a day, i.p.) for 4 days, starting 1 h before CP injection. Control rats were injected with 0.15 M NaCl or PAG only. Blood and urine samples were collected 5 days after saline or CP injections for renal function evaluation. the kidneys were removed for tumour necrosis factor (TNF)-alpha quantification, histological, immunohistochemical and Western blot analysis. the cystathionine gamma-lyase (CSE) activity and expression were assessed. the direct toxicity of H(2)S in renal tubular cells was evaluated by the incubation of these cells with NaHS, a donor of H(2)S.Results. CP-treated rats presented increases in plasma creatinine levels and in sodium and potassium fractional excretions associated with tubulointerstitial lesions in the outer medulla. Increased expression of TNF-alpha, macrophages, neutrophils and T lymphocytes, associated with increased H(2)S formation rate and CSE expression, were also observed in the outer medulla from CP-injected rats. All these alterations were reduced by treatment with PAG. A direct toxicity of NaHS for renal tubular epithelial cells was not observed.Conclusions. Treatment with PAG reduces the renal damage induced by CP. This effect seems to be related to the H2S formation and the restriction of the inflammation in the kidneys from PAG+CP-treated rats.