BXL 628 ameliorates toxicity of lactated Ringer in HK-2 human renal proximal tubule cells in a hypovolemia mimicking model

Introduction

Lactated Ringer (L/R) for resuscitation of hemorrhagic shock is suggested by the ATLS program. However, prior studies showed that resuscitation with L/R was associated with more kidney damage in rats with severe hemorrhagic shock. The direct effects of L/R on human renal tubule cells have not been reported.

Methods

Human proximal renal tubular cell line HK-2 was used. Viability was examined by MTT assay. An additional equal volume of phosphate- buffered saline (PBS) served as control. Addition of 200 nM dipyridyl and 1 mM H₂O₂ served as conditions of hypoxia and oxidative stress, respectively. Patterns of cell death were observed by flow cytometry.

Results

To imitate early resuscitation in hypovolemic shock, medium was replaced with 40% v/v of L/R with dipyridyl plus H₂O₂ for 4 hours, followed by replacing with complete medium for 44 hours. In such conditions, L/R augmented cytotoxicity, and more annexin V (+) cells were observed. Co-treatment or post-treatment with BXL 628, a novel VDR agonist, reversed L/R-induced cytotoxicity. See Figures 1 and 2.

Figure 1

Cell death of HK-2 cells after lactated Ringer administration in a hypovolemia mimic model.

Figure 2

Elocalcitol (BXL 628) ameliorates toxicity of lactated Ringer in HK-2 human renal tubule cells.

Conclusion

BXL 628 rescued L/R-induced apoptosis in human renal proximal tubule cells in a hypovolemia mimicking model.