Amelioration of tacrolimus-induced nephrotoxicity in rats using juniper oil

Lavjay Butani, Arash Afshinnik, Jeremy Johnson, Daniel Javaheri, Schonze Peck, J. Bruce German, Richard V Perez

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background. Calcineurin-inhibitor nephrotoxicity plays a role in the pathogenesis of chronic allograft nephropathy by causing renal ischemia mediated by vasoconstrictive metabolites of the prostanoid pathway. The purpose of our study was to evaluate whether altering the prostanoid profile using juniper oil (JO) would afford renoprotection in rats treated with tacrolimus. Methods. Diets supplemented with biologic oils (no supplementation, JO, fish oil [FO], safflower oil [SO], and arachidonic acid [AA]) were fed to five groups of rats for 5 weeks; during the last 2 weeks, tacrolimus was administered to all groups except for a control group of animals. At week 5, urinary prostaglandin (PG)F2-α and inulin clearances were measured. The rat kidneys were harvested to determine the renal cell membrane composition for arachidonic, eicosatrienoic, and eicosapentaenoic acids. Results. Both JO and FO completely reversed the decrease in inulin clearance seen with tacrolimus, the greatest effect being with JO (inulin clearance 15.1±3 vs. 6.0±1.1 ml/min in the nonsupplemented group; P<0.001); urinary PGF2-α excretion was also highest in the JO group (328±23 pg/mL, P<0.001 vs. the non-supplemented group). Fatty acid membrane analysis showed greatest incorporation of eicosapentaenoic and eicosatrienoic acids in the JO- (5.7±0.6% and 3.1±0.4%, respectively) and FO- (8.1±0.7% and 2.8±0.6%, respectively) treated animals. Conclusions. JO supplementation in tacrolimus-treated rats was associated with incorporation of vasodilatory prostanoids in the renal-cell membrane and elevated urinary PGF2-α excretion, and the precipitous fall in inulin clearance induced by tacrolimus was completely prevented. Whether this benefit will translate into a reduction in chronic allograft nephropathy remains to be determined. However, our preliminary data point towards the need for human trials.

Original languageEnglish (US)
Pages (from-to)306-311
Number of pages6
JournalTransplantation
Volume76
Issue number2
DOIs
StatePublished - Jul 27 2003

Fingerprint

Juniperus
Tacrolimus
Oils
Inulin
Dinoprost
Fish Oils
Prostaglandins
Kidney
Eicosapentaenoic Acid
Allografts
Cell Membrane
Safflower Oil
Arachidonic Acid
Fatty Acids
Ischemia
Diet
Control Groups
Membranes

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Amelioration of tacrolimus-induced nephrotoxicity in rats using juniper oil. / Butani, Lavjay; Afshinnik, Arash; Johnson, Jeremy; Javaheri, Daniel; Peck, Schonze; German, J. Bruce; Perez, Richard V.

In: Transplantation, Vol. 76, No. 2, 27.07.2003, p. 306-311.

Research output: Contribution to journalArticle

Butani, Lavjay ; Afshinnik, Arash ; Johnson, Jeremy ; Javaheri, Daniel ; Peck, Schonze ; German, J. Bruce ; Perez, Richard V. / Amelioration of tacrolimus-induced nephrotoxicity in rats using juniper oil. In: Transplantation. 2003 ; Vol. 76, No. 2. pp. 306-311.
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abstract = "Background. Calcineurin-inhibitor nephrotoxicity plays a role in the pathogenesis of chronic allograft nephropathy by causing renal ischemia mediated by vasoconstrictive metabolites of the prostanoid pathway. The purpose of our study was to evaluate whether altering the prostanoid profile using juniper oil (JO) would afford renoprotection in rats treated with tacrolimus. Methods. Diets supplemented with biologic oils (no supplementation, JO, fish oil [FO], safflower oil [SO], and arachidonic acid [AA]) were fed to five groups of rats for 5 weeks; during the last 2 weeks, tacrolimus was administered to all groups except for a control group of animals. At week 5, urinary prostaglandin (PG)F2-α and inulin clearances were measured. The rat kidneys were harvested to determine the renal cell membrane composition for arachidonic, eicosatrienoic, and eicosapentaenoic acids. Results. Both JO and FO completely reversed the decrease in inulin clearance seen with tacrolimus, the greatest effect being with JO (inulin clearance 15.1±3 vs. 6.0±1.1 ml/min in the nonsupplemented group; P<0.001); urinary PGF2-α excretion was also highest in the JO group (328±23 pg/mL, P<0.001 vs. the non-supplemented group). Fatty acid membrane analysis showed greatest incorporation of eicosapentaenoic and eicosatrienoic acids in the JO- (5.7±0.6{\%} and 3.1±0.4{\%}, respectively) and FO- (8.1±0.7{\%} and 2.8±0.6{\%}, respectively) treated animals. Conclusions. JO supplementation in tacrolimus-treated rats was associated with incorporation of vasodilatory prostanoids in the renal-cell membrane and elevated urinary PGF2-α excretion, and the precipitous fall in inulin clearance induced by tacrolimus was completely prevented. Whether this benefit will translate into a reduction in chronic allograft nephropathy remains to be determined. However, our preliminary data point towards the need for human trials.",
author = "Lavjay Butani and Arash Afshinnik and Jeremy Johnson and Daniel Javaheri and Schonze Peck and German, {J. Bruce} and Perez, {Richard V}",
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T1 - Amelioration of tacrolimus-induced nephrotoxicity in rats using juniper oil

AU - Butani, Lavjay

AU - Afshinnik, Arash

AU - Johnson, Jeremy

AU - Javaheri, Daniel

AU - Peck, Schonze

AU - German, J. Bruce

AU - Perez, Richard V

PY - 2003/7/27

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N2 - Background. Calcineurin-inhibitor nephrotoxicity plays a role in the pathogenesis of chronic allograft nephropathy by causing renal ischemia mediated by vasoconstrictive metabolites of the prostanoid pathway. The purpose of our study was to evaluate whether altering the prostanoid profile using juniper oil (JO) would afford renoprotection in rats treated with tacrolimus. Methods. Diets supplemented with biologic oils (no supplementation, JO, fish oil [FO], safflower oil [SO], and arachidonic acid [AA]) were fed to five groups of rats for 5 weeks; during the last 2 weeks, tacrolimus was administered to all groups except for a control group of animals. At week 5, urinary prostaglandin (PG)F2-α and inulin clearances were measured. The rat kidneys were harvested to determine the renal cell membrane composition for arachidonic, eicosatrienoic, and eicosapentaenoic acids. Results. Both JO and FO completely reversed the decrease in inulin clearance seen with tacrolimus, the greatest effect being with JO (inulin clearance 15.1±3 vs. 6.0±1.1 ml/min in the nonsupplemented group; P<0.001); urinary PGF2-α excretion was also highest in the JO group (328±23 pg/mL, P<0.001 vs. the non-supplemented group). Fatty acid membrane analysis showed greatest incorporation of eicosapentaenoic and eicosatrienoic acids in the JO- (5.7±0.6% and 3.1±0.4%, respectively) and FO- (8.1±0.7% and 2.8±0.6%, respectively) treated animals. Conclusions. JO supplementation in tacrolimus-treated rats was associated with incorporation of vasodilatory prostanoids in the renal-cell membrane and elevated urinary PGF2-α excretion, and the precipitous fall in inulin clearance induced by tacrolimus was completely prevented. Whether this benefit will translate into a reduction in chronic allograft nephropathy remains to be determined. However, our preliminary data point towards the need for human trials.

AB - Background. Calcineurin-inhibitor nephrotoxicity plays a role in the pathogenesis of chronic allograft nephropathy by causing renal ischemia mediated by vasoconstrictive metabolites of the prostanoid pathway. The purpose of our study was to evaluate whether altering the prostanoid profile using juniper oil (JO) would afford renoprotection in rats treated with tacrolimus. Methods. Diets supplemented with biologic oils (no supplementation, JO, fish oil [FO], safflower oil [SO], and arachidonic acid [AA]) were fed to five groups of rats for 5 weeks; during the last 2 weeks, tacrolimus was administered to all groups except for a control group of animals. At week 5, urinary prostaglandin (PG)F2-α and inulin clearances were measured. The rat kidneys were harvested to determine the renal cell membrane composition for arachidonic, eicosatrienoic, and eicosapentaenoic acids. Results. Both JO and FO completely reversed the decrease in inulin clearance seen with tacrolimus, the greatest effect being with JO (inulin clearance 15.1±3 vs. 6.0±1.1 ml/min in the nonsupplemented group; P<0.001); urinary PGF2-α excretion was also highest in the JO group (328±23 pg/mL, P<0.001 vs. the non-supplemented group). Fatty acid membrane analysis showed greatest incorporation of eicosapentaenoic and eicosatrienoic acids in the JO- (5.7±0.6% and 3.1±0.4%, respectively) and FO- (8.1±0.7% and 2.8±0.6%, respectively) treated animals. Conclusions. JO supplementation in tacrolimus-treated rats was associated with incorporation of vasodilatory prostanoids in the renal-cell membrane and elevated urinary PGF2-α excretion, and the precipitous fall in inulin clearance induced by tacrolimus was completely prevented. Whether this benefit will translate into a reduction in chronic allograft nephropathy remains to be determined. However, our preliminary data point towards the need for human trials.

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