Journal of Experimental Pharmacology (Oct 2020)
Effect of Kaempferol on Tacrolimus-Induced Nephrotoxicity and Calcineurin B1 Expression Level in Animal Model
Abstract
Ahmed Shaker Ali,1,2 Abdullah Saddah Almalki,1,3 Basma Tarek Alharthy1 1Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt; 3Department of Pharmacy, Ajyad Hospital, Ministry of Health, Riyadh, Saudi ArabiaCorrespondence: Abdullah Saddah Almalki Makkah 24268 – 9382, Kingdom of Saudi ArabiaTel +966 126401000 - Ext 20151Fax +966 126400855Email [email protected]: 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.Keywords: FK506, kaempferol, calcineurin B1, nephrotoxicity, biomarkers
