Abstract
Chronic kidney disease (CKD) poses significant challenges to public health and is a key contributing factor to cardiovascular disease. Research performed at the University of Otago found the anti-diuretic drug amiloride reduced kidney fibrosis in three rat models. How amiloride reduces kidney fibrosis is uncertain. Additional research suggests that impaired fatty acid oxidation (FAO) leads to fibrosis. This study aimed to determine if amiloride could restore CPT1?? (fatty acid mediator) expression in CKD rat kidney tissue.
Kidney tissue from two CKD models (folic acid and adenine) treated with and without amiloride, and control tissues (amiloride or vehicle control only) with n=8 for each group were selected. Tissue sections were stained with an anti-CPT1?? antibody using immunohistochemistry. Stained slides were digitally scanned, and positive pixels counted using ImageJ software. Three different thresholds captured the different staining intensities of CPT1??: strong, moderate, and weak. The data collected was subject to a One-Way ANOVA, corrected for multiple comparisons.
CPT1?? using the strong threshold was significantly increased in rats treated with amiloride and adenine compared to adenine alone with a mean positive pixel count of 838634 for the amiloride and adenine group, versus 378359 pixels for the adenine group per x200 magnification field (P = 0.0072). Consequently, it caused significantly less weak staining when compared to the control (P = 0.0015).
Within the moderate threshold, folic acid significantly reduced CPT1?? levels compared to the control (P = 0.0009). Additionally, the amiloride and folic acid group approached control levels with a mean of 271442 versus 323667 pixels per x200 magnification.
These findings suggest amiloride can restore CPT1?? in fibrotic kidney tissue. This may be protective against impaired FAO, which may contribute to the reduction in kidney fibrosis. Suggesting that amiloride could serve as a potential treatment for those with CKD.