Cyclic adenosine monophosphate protects renal cell lines against amphotericin B toxicity in a PKA-independent manner

Abstract

Amphotericin B is the “gold standard” agent in the management of serious systemic fungal infections. However, this drug can cause nephrotoxicity, which contributes up to 25% of all acute kidney injuries in critically ill patients. Cyclic adenosine monophosphate can protect kidney cells from death due to injury or drug exposure in some cases. Hence, the objective of this work was to evaluate if cAMP could prevent cell death that occurs in renal cell lines subjected to AmB treatment and, if so, to assess the involvement of PKA in the transduction of this signal. Two different renal cell lines (LLC-PK1 and MDCK) were used in this study. MTT and flow cytometry assays showed increased cell survival when cells were exposed to cAMP in a PKA-independent manner, which was confirmed by western blot. This finding suggests that cAMP (db-cAMP) may prevent cell death caused by exposure to AmB. This is the first time this effect has been identified when renal cells are exposed to AmB’s nephrotoxic potential.

Keywords:

• cAMP
• cell protection
• nephrotoxicity

Acknowledgements

The authors thank Gláucia A. A. Carvalho for excellent technical assistance.

Declaration of interest

The authors report that they have no conflicts of interest. UFMG (Universidade Federal de Minas Gerais), UFOP (Universidade Federal de Ouro Preto), FAPEMIG (Fundação de Amparo e Pesquisa de Minas Gerais Log Number: APQ-00596-08), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), and CNPQ (Conselho Nacional de Pesquisa) supported this paper.