Chlorogenic acid attenuates kidney fibrosis via antifibrotic action of bmp-7 and hgf

Background: Kidney fibrosis, characterised by tubulointerstitial fibrosis, is a histological landmark of chronic kidney disease. The body attempts to compensate for progressive detrimental process of kidney fibrosis by producing antifibrotic substances, such as bone morphogenetic protein-7 (BMP-7) and hepatocyte growth factor (HGF). Chlorogenic acid is known to have renoprotective and antifibrotic properties. This study aims to evaluate the effect of chlorogenic acid on unilateral ureteral obstruction (UUO)-induced kidney fibrosis mice model. Methods: This study was a quasi-experimental with posttest-only control group design. Twenty-five adult male Swiss Webster mice were randomly divided into five groups: sham-operated group (SO), UUO-control day-7 (U7), UUO-control day-14 (U14), UUO-chlorogenic acid day-7 (UC7), and UUO-chlorogenic acid day 14 (UC14). Myofibroblasts were identified by immunohistochemical staining of alpha-smooth muscle actin (α-SMA) while collagen fibers were identified by Sirius Red staining. Both data were presented as area fraction. BMP-7 and HGF mRNA expressions were assessed by reverse transcription PCR (RT-PCR). Data were quantified using ImageJ software. Results: UUO-control groups (U7 and U14) showed higher α-SMA-immunopositive (6.52±1.33, 18.24±1.39 vs. 0.22±0.01; p<0.05) and Sirius Red-positive area fractions (6.61±0.8, 12.98±2.31 vs. 0.62±0.10; p<0.05), lower BMP-7 (1.02±0.47, 1.18±0.65 vs. 2.09±0.87; p<0.05) and HGF mRNA expressions (1.06±0.31, 0.89±0.14 vs. 1.88±0.81; p<0.05) compared to SO group. UUO-chlorogenic acid groups (UC7 and UC14) showed lower α-SMA-immunopositive (1.24±0.37, 4.58±0.61; p<0.05) and Sirius Red-positive area fractions (4.76±1.03, 3.72±0.54; p<0.05), higher BMP-7 (1.84±0.49, 2.19±0.43; p<0.05) and HGF (1.58±0.38; p>0.05, 1.84±0.42; p<0.05) mRNA expressions compared to UUO-control groups. UUO-chlorogenic acid groups showed BMP-7 and HGF mRNA expressions that were not significantly different from the SO group. Conclusion: Chlorogenic acid administration prevents kidney fibrosis in UUO mice model through modulating antifibrotic pathway. © 2020 Elsevier B.V., All rights reserved.