Porcine proximal tubular cells (LLC-PK1) are able to tolerate high levels of lithium chloride in vitro: assessment of the influence of 1-20 mM LiCl on cell death and alterations in cell biology and biochemistry.
Lithium, a prophylactic drug for the treatment of bipolar disorder, is prescribed with caution due to its side effects, including renal damage. In this study porcine LLC-PK1 renal tubular cells were used to establish the direct toxicity of lithium on proximal cells and gain insights into the molecular mechanisms involved. In the presence of LiCl, cell proliferation exhibited insignificant decreases in a concentration-dependent manner, but once confluent, constant cell numbers were observed. Cell cycle studies indicated a small dose-dependent accumulation of cells in the G2/M stage after 24 h, as well as an increase in cells in the G0/G1 phase after treatment with 1-10 mM LiCl, but not at 20 mM LiCl. No evidence of apoptosis was observed based on cell morphology or DNA fragmentation studies, or evidence of protein expression changes for Bax, Bcl-2, and p53 proteins using immunocytochemistry. In addition caspases 3, 8 and 9 activity remained unaltered between control and lithium-treated cultures. To conclude, exposure to high concentrations of lithium did not result in overt toxic effects to LLC-PK1 renal cells, although LiCl did alter some aspects of cell behaviour, which could potentially influence function over time.
Lucas
Kirsten C
KC
Department of Biochemistry, Microbiology and Biotechnology, School of Molecular and Life Sciences, University of Limpopo, P/Bag X1106 Sovenga, 0727, South Africa. kirstenl@ul.ac.za
Hart
David A
DA
Becker
Rolf W
RW
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002455:Cell Division; D016193:G1 Phase; D016195:G2 Phase; D018374:LLC-PK1 Cells; D018021:Lithium Chloride / Q000633:toxicity*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D016160:Retinoblastoma Protein / Q000378:metabolism; D013552:Swine; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D018021:Lithium Chloride