Changes of concentrations, shipment amounts and ecological risk of pesticides in river water flowing into Lake Biwa.

A survey of various pesticide contaminations was performed for water in Yanamune River flowing into Lake Biwa from 1988 to 2009. Ten pesticides (diazinon and fenitrothion as insecticides, iprobenfos and isoprothiolane as fungicides and chlornitrofen, thiobencarb, molinate, bromobutide, simetryne and pretilachlor as herbicides) were selected and concentration changes of the pesticides were evaluated based on their shipment amounts. Yearly maximum concentrations of eight of the pesticides in Yanamune River water were compared with their no observed effect concentration and their predicted no effect concentration values and initial ecological risk assessment was conducted for five pesticides (diazinon, fenitrothion, iprobenfos, isoprothiolane and thiobencarb) by their predicted no effect concentration values. All of the diazinon (0.01-0.28 µg/L) and fenitrothion (0.005-0.31 µg/L) concentrations from 1988 to 2007, the iprobenfos (2.7 and 2.4 µg/L) concentrations in 1988 and 1990 and the thiobencarb (0.24-2.7 µg/L) concentrations in 1988, 1992, 1993 and 1995 exceeded their predicted no effect concentration (PNEC) (0.00026, 0.00021, 1.0 and 0.17 µg/L) values.

Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes.

AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) has various extra-pancreatic actions, in addition to its enhancement of insulin secretion from pancreatic beta cells. The GLP-1 receptor is produced in kidney tissue. However, the direct effect of GLP-1 on diabetic nephropathy remains unclear. Here we demonstrate that a GLP-1 receptor agonist, exendin-4, exerts renoprotective effects through its anti-inflammatory action via the GLP-1 receptor without lowering blood glucose. METHODS: We administered exendin-4 at 10 µg/kg body weight daily for 8 weeks to a streptozotocin-induced rat model of type 1 diabetes and evaluated their urinary albumin excretion, metabolic data, histology and morphometry. We also examined the direct effects of exendin-4 on glomerular endothelial cells and macrophages in vitro. RESULTS: Exendin-4 ameliorated albuminuria, glomerular hyperfiltration, glomerular hypertrophy and mesangial matrix expansion in the diabetic rats without changing blood pressure or body weight. Exendin-4 also prevented macrophage infiltration, and decreased protein levels of intercellular adhesion molecule-1 (ICAM-1) and type IV collagen, as well as decreasing oxidative stress and nuclear factor-κB activation in kidney tissue. In addition, we found that the GLP-1 receptor was produced on monocytes/macrophages and glomerular endothelial cells. We demonstrated that in vitro exendin-4 acted directly on the GLP-1 receptor, and attenuated release of pro-inflammatory cytokines from macrophages and ICAM-1 production on glomerular endothelial cells. CONCLUSIONS/INTERPRETATION: These results indicate that GLP-1 receptor agonists may prevent disease progression in the early stage of diabetic nephropathy through direct effects on the GLP-1 receptor in kidney tissue.