Cyclosporine A and the potential nephroprotective effect of pomegranate juice in rats.
Keywords:
Pharmacokinetics, pomegranate juic, ; CsA; food-drug interaction;, P-glycoprotein efflux pump (P- gp);, CYP3A4; nephroprotective.Abstract
The purpose of this research was to examine the possible nephroprotective impact of pomegranate juice (PJ) against
cyclosporine A (CsA) caused nephrotoxicity by examining the effect of contemporaneous administration of PJ on
bioavailability of CsA.
Methods: A- In a pharmacokinetic (PK) investigation, groups of 6 Wister rats were used. CsA PO + Vehicle (I),
CsA IP + Vehicle (II), CsA PO + PJ (III), and CsA IP + PJ (IV). The CsA dosage was 20 mg/kg daily for 5 days,
and the PJ dose was 2 ml given 1 hour before each dose. CsA levels were measured using immunological assays
from blood samples collected at the beginning and end of day 1. CsA's relative bioavailability was calculated.
I- (CsA 13 mg PO + 2 ml PJ), and B- (nephroprotection research; a separate trial to give bioequivalent CsA PO
dosages, in light of PK study).To administer CsA, mix 20 mg of P0 with 2 ml of vehicle (for 28 days). Two control
groups (vehicle alone and PJ only) are also included within the design. At the 28th day, samples of bloo d and urine
were collected for histology, biochemistry, and drug analyses.
As a result, the bioavailability of oral CsA was increased by around 50% (P > 0.05) when combined with PJ juice.
However, 5 days of continuous treatment of CsA (IP) had no effect. Parallel delivery of PJ restored the severe renal
damage caused by CsA and suppressed the accompanying rise in serum creatinine.
Repeated dosing with pomegranate juice increases oral bioavailability of CsA, most likely by blocking enzymes and
transport pumps in the intestines. It significantly mitigated the renal damage generated by CsA when administered
alone.
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