The combined effects of
glyphosate and hard water on
chronic kidney disease of unknown etiology (CDKu) have attracted much interest, but the mechanisms remain unknown. Cytoplasmic
phospholipase A2 (cPLA2) plays a key role in the acute and chronic inflammatory reactions. This study explored the effect of
glyphosate combined with hard water on renal tubules and the possible targets and mechanisms involved.
METHODS: Administration of
glyphosate in mice resulted in elevated levels of β2-microglobulin (β2-MG),
albumin (ALB), and serum
creatinine (SCr) compared to control mice. This increase was more pronounce when
glyphosate was combined with hard water. In the
glyphosate-treated mice, small areas of the kidney revealed fibroblast proliferation and vacuolar degeneration, particularly at the higher dose of 400 mg/kg
glyphosate. However, the combination of
glyphosate and hard water induced an even greater degree of pathological changes in the kidney. Immunofluorescence and western blot analyses showed that
glyphosate and hard water had a coordinated effect on
calcium ions (Ca2+)-activated
phospholipase A2 and the activation may play a key role in
inflammation and renal tubular injury. Exposure to
glyphosate alone or
glyphosate plus hard water increased the levels of oxidative stress markers and inflammatory
biomarkers, namely,
thromboxane A2 (TX-A2),
leukotriene B4 (
LTB4),
prostaglandin E2 (
PGE2),
nitric oxide synthase (NOS), and
nitric oxide (NO). Parameters of oxidative stress, including the levels of
superoxide dismutase (SOD) and
glutathione peroxidase (GSH-Px) were decreased. Further analysis showed that the levels of these
biomarkers were significantly different between the mice treated with
glyphosate plus hard water and the mice treated with
glyphosate alone.
CONCLUSIONS: