Abstract
Amphotericin B‐deoxycholate (Fungizone [FZ]) is a widely used potent antimycotic drug in spite of its nephrotoxic effect via different mechanisms. The effect of FZ on renal cell bioenergetics is not clear. The current study evaluated the effect of FZ on the bioenergetics of albino rats' isolated renal proximal tubule cells (PTCs). The cytotoxic effect of FZ on the isolated renal cells was assessed by MTT and lactate dehydrogenase (LDH) assays. The effect of FZ on the PTCs uptake (OAT1 and OCT2) and efflux (P‐gp and MRP2) transporters was evaluated. Then, the effect of FZ on mitochondria was assessed by studying complexes I–IV activities, lactate assay, oxygen consumption rates (OCR), and western blotting for all mitochondrial complexes. Moreover, the effect of FZ on mitochondrial membrane fluidity (MMF) and fatty acids composition was evaluated. Additionally, the protective effect of coenzyme q10 was studied. Outcomes showed that FZ was cytotoxic to the PTCs in a concentration and time‐dependent patterns. FZ significantly inhibited the studied uptake and efflux tubular transporters with inhibition of the mitochondrial complexes activities and parallel increase in lactate production and decrease in OCRs. Finally, FZ significantly reduced the expression of all mitochondrial complexes in addition to significant increase in MMF and MMFA concentration. Coenzyme Q10 was found to significantly decrease FZ‐induced cytotoxicity and transporters impairment in the PTC. FZ significantly inhibits bioenergetics of PTC, which may stimulate the cascade of cell death and clinical nephrotoxicity.
Fungizone significantly inhibits mitochondrial bioenergetics of the renal proximal tubular cells with significant functional impairment. This mitochondrial dysfunction may stimulate the cascade of cell death and clinical nephrotoxicity. Coenzyme Q10 was found to significantly decrease Fungizone‐induced cytotoxicity and transporters impairment in the PTC.