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 language | English (US) |
|---|---|
| Pages (from-to) | 306-311 |
| Number of pages | 6 |
| Journal | Transplantation |
| Volume | 76 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 27 2003 |
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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 journal › Article
}
TY - JOUR
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
Y1 - 2003/7/27
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.
UR - http://www.scopus.com/inward/record.url?scp=0042768045&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042768045&partnerID=8YFLogxK
U2 - 10.1097/01.TP.0000072337.37671.39
DO - 10.1097/01.TP.0000072337.37671.39
M3 - Article
C2 - 12883183
AN - SCOPUS:0042768045
VL - 76
SP - 306
EP - 311
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 2
ER -