title: Hydrogen sulphide as a novel therapy to ameliorate cyclosporine nephrotoxicity.
abstract: BACKGROUND
  Calcineurin inhibitors have significant nephrotoxic side effects, which can exacerbate ischemia-reperfusion injury in renal transplantation. Novel therapeutic agents such as hydrogen sulphide (H₂S) may reduce these harmful effects. This study investigated the effects of H₂S on cyclosporine (CsA) induced nephrotoxicity.
  
  
  METHODS
  Porcine kidneys were subjected to 15 min of warm ischemia and 2 h of static cold storage. They were reperfused for 3 h with oxygenated normothermic autologous whole blood on an isolated organ reperfusion apparatus. Kidneys were treated with CsA during reperfusion (n = 6) or cyclosporine and 0.25 mmol/L of H₂S infused 10 min before and 20 min after reperfusion (n = 6). These were compared with untreated controls (n = 7).
  
  
  RESULTS
  CsA caused a significant reduction in renal blood flow during reperfusion, which was reversed by H₂S (area under the curve renal blood flow CsA 257 ± 93 versus control 477 ± 206 versus CsA + H₂S 478 ± 271 mL/min/100 g.h; P = 0.024). Urine output was higher after 2 h of reperfusion in the CsA + H₂S group (CsA + H₂S 305 ± 218 versus CsA 78 ± 180 versus control 210 ± 45 mL; P = 0.034). CsA treatment was associated with an increase in tubular injury, which was not reversed by H₂S (area under the curve fractional excretion of sodium, control 77 ± 53 versus CsA 100 ± 61 versus CsA + H2S 111 ± 57%.h; P = 0.003). Histologic evaluation showed significant vacuolation and glomerular shrinkage in the CsA group. These were significantly reduced by H₂S (P = 0.005, 0.002).
  
  
  CONCLUSIONS
  H₂S reversed the vasoconstriction changes associated with CsA treatment during reperfusion.
authors.affiliation: Department of Infection, Immunity and Inflammation, Transplant Group, The University of Leicester, Leicester General Hospital, Leicester, United Kingdom. Electronic address: gwynlee@hotmail.co.uk.
authors.forename: Gwyn
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Infection, Immunity and Inflammation, Transplant Group, The University of Leicester, Leicester General Hospital, Leicester, United Kingdom.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Hosgood
authors.affiliation: Department of Infection, Immunity and Inflammation, Transplant Group, The University of Leicester, Leicester General Hospital, Leicester, United Kingdom.
authors.forename: Meeta S
authors.initials: MS
authors.lastname: Patel
authors.affiliation: Department of Infection, Immunity and Inflammation, Transplant Group, The University of Leicester, Leicester General Hospital, Leicester, United Kingdom.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nicholson
mesh_terms: D000818:Animals; D065095:Calcineurin Inhibitors / Q000009:adverse effects*; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D006862:Hydrogen Sulfide / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy*; D013552:Swine; D016896:Treatment Outcome; D014661:Vasoconstriction / Q000187:drug effects; D052096:Warm Ischemia
chemical_list: D065095:Calcineurin Inhibitors; D020011:Protective Agents; D016572:Cyclosporine; D006862:Hydrogen Sulfide
keywords: Cyclosporine; Hydrogen sulphide; Ischemia–reperfusion injury; Kidney