Inhibition of hydrogen sulphide formation reduces cisplatin-induced renal damage.
BACKGROUND
Cisplatin (CP)-induced renal damage is associated with inflammation. Hydrogen sulphide (H2S) is involved in models of inflammation. This study evaluates the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S 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)-α quantification, histological, immunohistochemical and Western blot analysis. The cystathionine γ-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 H2S.


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-α, macrophages, neutrophils and T lymphocytes, associated with increased H2S 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.
Della Coletta Francescato
Heloísa
H
E-mail: tmcoimbr@fmrp.usp.br.
Cunha
Fernando Queiroz
FQ
Costa
Roberto Silva
RS
Barbosa Júnior
Fernando
F
Boim
Mirian Aparecida
MA
Arnoni
Carine Prisco
CP
da Silva
Cleonice Giovanini Alves
CG
Coimbra
Terezila Machado
TM
D000480:Alkynes / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000037:antagonists & inhibitors*; D007249:Inflammation; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced; D051381:Rats
D000480:Alkynes; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C009055:propargylglycine; D002945:Cisplatin; D005998:Glycine; D006862:Hydrogen Sulfide