TY - JOUR
T1 - Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations
AU - Cárdenas-González, Mariana C.
AU - Del Razo, Luz M.
AU - Barrera-Chimal, Jonatan
AU - Jacobo-Estrada, Tania
AU - López-Bayghen, Esther
AU - Bobadilla, Norma A.
AU - Barbier, Olivier
N1 - Funding Information:
This study was supported by the Mexican Council for Science and Technology (Conacyt 152416 to OB) and the National University of Mexico ( IN203412-3 to NAB). The technical assistance of Angel Barrera-Hernández, Luz Del Carmen Sánchez Peña, Juana Narváez Morales and Rosalba Pérez Villava is deeply appreciated. Mariana C. Cárdenas-González and Jonatan Barrera-Chimal are the recipients of a scholarship from the Conacyt (206963 and 229323, respectively).
PY - 2013/11/1
Y1 - 2013/11/1
N2 - Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25. ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15. ppm) and high (50. ppm) fluoride concentrations in drinking water for a period of 40. days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride.
AB - Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25. ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15. ppm) and high (50. ppm) fluoride concentrations in drinking water for a period of 40. days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride.
KW - Early biomarker
KW - Fluoride
KW - Kidney injury
KW - Kim-1
KW - Sub-chronic exposure
KW - Urinary biomarkers
UR - http://www.scopus.com/inward/record.url?scp=84884705075&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2013.07.026
DO - 10.1016/j.taap.2013.07.026
M3 - Artículo
C2 - 23933529
SN - 0041-008X
VL - 272
SP - 888
EP - 894
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 3
ER -