Effect of Kaempferol on Tacrolimus-Induced Nephrotoxicity and Calcineurin B1 Expression Level in Animal Model.
J Exp Pharmacol
; 12: 397-407, 2020.
Article
en En
| MEDLINE
| ID: mdl-33149706
ABSTRACT
BACKGROUND:
The kidneys are considered one of the most susceptible organs for adverse drug effects, particularly in post-transplant conditions. Tacrolimus (FK506), a calcineurin inhibitor immunosuppressant, is an essential component in the transplantation regimen. Despite that, nephrotoxicity is a severe drawback for its chronic utilization, where oxidative stress might be implicated. Kaempferol (KMF) is a natural flavonoid that has many adaptable biological activities, including antioxidant action.OBJECTIVE:
Exploring the KMF protective effect on FK506-induced nephrotoxicity and the underlying role of calcineurin B1.METHODS:
Twenty-four male albino-Wistar rats were randomly divided into three equal groups. The control group received solvents propylene glycol, i.p. and 0.5% carboxymethyl cellulose, PO; FK506 group was injected with FK506 (0.6 mg/kg, i.p.), and FK506+KMF group was given FK506 (0.6 mg/kg, i.p.) and KMF (10 mg/kg, PO). The treatment regimen for all groups was once daily for 30 days. ELISA technique applied for measuring FK506 trough level and nephrotoxicity biomarkers in serum (cystatin C and urea) on days 15 and 30, and in kidney tissue homogenate (MDA and calcineurin B1) on day 30.RESULTS:
In FK506-treated rats, the FK506 trough level was 7.84 ± 1.31 ug/l on day 15 and 9.54 ± 1.45 ug/l on day 30. FK506 use has significantly (P<0.01) increased biomarkers levels of cystatin C (325% and 477%), urea (177% and 245%), MDA (1253%), except calcineurin B1 that has decreased (97%). The KMF combination has resulted in a significant reduction in the FK506 trough level by day 30 (6.79 ± 1.35 ug/l, P<0.01). KMF has significantly ameliorated the levels of cystatin C (46% and 73%, P<0.001), urea (38% and 68%, P<0.001), MDA (75%, P<0.001), and calcineurin B1 (1833%, P<0.05).CONCLUSION:
Oxidative stress and calcineurin B1 are contributing factors in FK506-induced nephrotoxicity. Hence, inhibition of calcineurin enzyme is not limited to the immune cells. KMF could be a novel nephroprotective antioxidant.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Exp Pharmacol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Arabia Saudita