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 posttestonly control group design. Twenty-five adult male Swiss Webster mice were randomly divided into five groups: shamoperated group (SO), UUO-control day-7 (U7), UUO-control day-14 (U14), UUO-chlorogenic acid day-7 (UC7), and UUOchlorogenic acid day 14 (UC14). Myofibroblasts were identified by immunohistochemical staining of alphasmooth 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. UUOchlorogenic 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.

Global pollution monitoring of butyltin compounds using skipjack tuna as a bioindicator.

Butyltin compounds (BTs) including mono- (MBT), di- (DBT), tri-butyltin (TBT) and total tin (sigmaSn), were determined in the liver of skipjack tuna (Katsuwonus pelamis) collected from Asian offshore waters (off-Japan, the Japan Sea, off-Taiwan, the East China Sea, the South China Sea, off-Philippines, off-Indonesia, the Bay of Bengal), off-Seychelles, off-Brazil and open seas (the North Pacific). BTs were detected in all the skipjack tuna collected, suggesting widespread contamination of BTs even in offshore waters and open seas on a global scale. Considering specific accumulation, Sex-, body length- differences and migration of skipjack tuna did not seem to affect BT concentrations, indicating rapid reflection of the pollution levels in seawater where and when they were collected. Skipjack tuna is a suitable bioindicator for monitoring the global distribution of BTs in offshore waters and open seas. High concentrations of BTs were observed in skipjack tuna from offshore waters around Japan, a highly developed and industrialized region (up to 400 ng/g wet weight). Moreover skipjack tuna collected from offshore waters around Asian developing countries also revealed the levels comparable to those in Japan (up to 270 ng/g wet weight) which may be due to the recent improvement in economic status in Asian developing countries. High percentages (almost 90%) of BTs in total tin (sigmaSn: sum of inorganic tin+organic tin) were found in the liver of skipjack tuna from offshore waters around Asian developing countries. This finding suggests that the anthropogenic BTs represent the major source of Sn accumulation in skipjack tuna from these regions.

Global pollution monitoring of PCBs and organochlorine pesticides using skipjack tuna as a bioindicator.

Concentrations of organochlorines (OCs) representing persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), dichlorodiphenyl trichloroethane and its metabolites (DDTs), chlordane compounds (CHLs), hexachlorocyclohexane isomers (HCHs), and hexachlorobenzene (HCB), were determined in the liver of skipjack tuna (Katsuwonus pelamis) collected from the offshore waters of various regions in the world (offshore waters around Japan, Taiwan, Philippines, Indonesia, Seychelles, and Brazil, and the Japan Sea, the East China Sea, the South China Sea, the Bay of Bengal, and the North Pacific Ocean). OCs were detected in livers of all of the skipjack tuna collected from the locations surveyed, supporting the thesis that there is widespread contamination of persistent OCs in the marine environment. Within a location, no significant relationship between growth-stage (body length and weight) and OC concentrations (lipid weight basis) was observed, and the OC residue levels were rather uniform among the individuals. Interestingly, the distribution of OC concentrations in skipjack tuna was similar to those in surface seawaters from which they were taken. These results suggest that OC concentrations in skipjack tuna could reflect the pollution levels in seawater from which they are collected and that this species is a suitable bioindicator for monitoring the global distribution of OCs in offshore waters and the open ocean. Concentrations of PCBs and CHLs in skipjack tuna were higher in offshore waters around Japan (up to 1100 and 250 ng/g lipid wt, respectively), suggesting the presence of sources of PCBs and CHLs in Japan. High concentrations of DDTs and HCHs were observed in samples from the Japan Sea, the East China Sea, the South China Sea, and the Bay of Bengal (up to 1300 and 22 ng/g lipid wt, respectively). This result suggests recent use of technical DDT and HCH for agricultural and/or public health purposes in Russia, China, India, and some other developing Asian countries. Relatively high concentrations of PCBs, CHLs, HCHs, and HCB were also observed in samples collected from some locations in the middle of the Pacific Ocean, indicating the expansion of OC contamination on a global scale. Considering these facts, continuous studies monitoring these compounds in offshore waters and the open seas, using skipjack tuna as a bioindicator, are needed to further understand the future trend of contamination.