PATHOPHYSIOLOGICAL RESPONSE OF RHESUS MONKEY KIDNEY EPITHELIAL CELLS EXPOSED TO CYCLOSPORINE A

摘要

Cyclosporine A (CsA) is extracted from Tolypocladium inflatum Gains, which is metabolized through the superfamily of hepatic isoenzymes P-450. CsA has a mean life of 6.4-8.7 h, although this varies among different individuals. Ninety percent of the drug is excreted through biliary excretion and only 6% appears unchanged in the urine. The exact mechanism of action of CsA is unknown; however, CsA has the ability to act on the immune system by blocking the biosynthesis of some lymphokines produced by T lymphocytes and interlenkin-2 synthesis at the transcriptional level. It has been suggested that CsA interacts with the cytoplasmic membrane and activates the intracellular calcium pathway, or binds to cytoplasmic proteins (Parra, 2003). The specific objective of this study was to investigate the effects of various concentrations of CsA on the proliferation and viability of Rhesus Monkey Kidney epithelial cells (RMKEC) in culture. Thirty-five wells were plated with RMKEC and sub-divided into five equal groups. Group 2 was treated with 10mL of ETOH (vehicle for CsA). Groups 3-5, were treated with 10, 25, and 50 μM of CsA, respectively. Data obtained suggests that: (1) there was no significance difference observed using CsA 10 μM and CsA 25 μM in comparison to the control, (2) the use of 50 μM CsA suppressed cell proliferation in comparison to the control and caused an increase in all biochemical markers (MDA, Protein, and Nitric oxide), (3) the vehicle resulted in an increase in cell proliferation and a decrease in the biochemical markers MDA and Glutathione. The data suggests that further studies need to be conducted to determine the full impact of CsA on Kidney Epithelial function.