Benefit of theophylline administration in tacrolimus-induced nephrotoxicity in rats

Gwenn E McLaughlin, Michelle Schober, Maria Perez, Phillip Ruiz, Bernard W Steele, Carolyn Abitbol

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Tacrolimus (TAC), a widely used nephrotoxic calcineurin inhibitor, is associated with renal vasoconstriction possibly through adenosine receptor activation. Theophylline (THEO), an adenosine receptor inhibitor, protects against the nephrotoxicity of drugs associated with renal vasoconstriction. We hypothesized that co-administration of low dose THEO in rats would prevent TAC-induced nephrotoxicity. Sprague-Dawley rats pair-fed a low-sodium diet were randomized into three groups (n=10/group): the control (CONTROL) group received the vehicle for both medications; the TAC group received TAC 6 mg/kg/day and vehicle; and the TAC+THEO group received TAC and THEO 17 mg/kg/day. On day 21, a timed urine collection was obtained for creatinine clearance. On day 22, serum creatinine, THEO and whole blood TAC concentrations were determined. One kidney was removed for formalin fixation and histological assessment. In the TAC group, serum creatinine increased while creatinine clearance decreased compared to CONTROL (0.3±0.0 vs. 0.4±0.0 mg/dl and 0.53±0.06 vs. 0.34±0.04 ml/min/100 g body weight respectively, p<0.05), while TAC+THEO did not differ from control. There were no significant differences in renal histology. Concurrent administration of low-dose THEO prevented the TAC-induced decline in renal function, consistent with a role for adenosine in TAC-induced nephrotoxicity.

Original languageEnglish
Pages (from-to)860-864
Number of pages5
JournalPediatric Nephrology
Volume18
Issue number9
DOIs
StatePublished - Sep 1 2003

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Tacrolimus
Theophylline
Creatinine
Kidney
Purinergic P1 Receptors
Vasoconstriction
Sodium-Restricted Diet
Urine Specimen Collection
Serum
Adenosine
Formaldehyde
Sprague Dawley Rats
Histology
Body Weight
Control Groups

Keywords

  • Adenosine
  • Calcineurin inhibitor
  • Creatinine
  • Creatinine clearance
  • Nephrotoxicity
  • Tacrolimus
  • Theophyline

ASJC Scopus subject areas

  • Nephrology
  • Pediatrics, Perinatology, and Child Health

Cite this

Benefit of theophylline administration in tacrolimus-induced nephrotoxicity in rats. / McLaughlin, Gwenn E; Schober, Michelle; Perez, Maria; Ruiz, Phillip; Steele, Bernard W; Abitbol, Carolyn.

In: Pediatric Nephrology, Vol. 18, No. 9, 01.09.2003, p. 860-864.

Research output: Contribution to journalArticle

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