Cyclosporine nephrotoxicity in the ischemic kidney and the protective effect of pentoxifylline--a study in the rat.
In order to prevent cyclosporine nephrotoxicity in the ischemic kidney, pentoxifylline was used in a rat model. Seventy-two rats were divided into six groups according to treatment after right nephrectomy: Group I was the control, group II was treated with 25 mg/kg cyclosporine, group III underwent renal ischemia for 45 min, group IV was given 25 mg/kg cyclosporine and subjected to renal ischemia, and group V was subjected to renal ischemia and given 45 mg/kg pentoxifylline (repeated at 12, 36, and 48 hr), group VI underwent renal ischemia and was then given both cyclosporine and pentoxifylline. BUN, creatinine, and potassium levels were significantly elevated 24 hr after cyclosporine (group II), ischemia (group III), and cyclosporine and ischemia (group IV). Sodium levels remained unaffected. BUN levels normalized in all but groups III and IV after 48 hr. Creatinine levels normalized in all but group IV after 48 hr. Creatinine clearance fell in all groups and remained low even after 48 hr. Pentoxifylline prevented dramatic rises in BUN and creatinine and levels nearly normalized after 48 hr. It also histologically prevented extensive tissue damage seen after ischemia. In conclusion, pentoxifylline has a protective effect upon the kidney when subjected to cyclosporine in the presence of ischemia.
Ates
E
E
Department of Surgery, Faculty of Medicine, Osmangazi University, Eskisehir, Turkey.
Sharma
P
P
Erkasap
S
S
Talbot
D
D
Ihtiyar
E
E
Yasar
B
B
Kiper
H
H
D000818:Animals; D002114:Calcinosis / Q000139:chemically induced; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000633:toxicity*; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008026:Ligation; D008833:Microcirculation / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000502:physiology; D014617:Vacuoles / Q000648:ultrastructure; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D011453:Prostaglandins; D014665:Vasodilator Agents; D013928:Thromboxane A2; D016572:Cyclosporine; D003404:Creatinine; D010431:Pentoxifylline