TY - JOUR
T1 - Apocynin combined with drugs as coadjuvant could be employed to prevent and/or treat the chronic kidney disease
AU - Montes-Rivera, Jorge Osvaldo
AU - Tamay-Cach, Feliciano
AU - Quintana-Pérez, Julio César
AU - Guevara-Salazar, Juan Alberto
AU - Trujillo-Ferrara, José Guadalupe
AU - Del Valle-Mondragón, Leonardo
AU - Arellano-Mendoza, Mónica Griselda
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/10/15
Y1 - 2018/10/15
N2 - A worldwide public health problem is chronic kidney disease (CKD) presenting alarming epidemiological data. It currently affects about 10% of the adult population worldwide and has a high mortality rate. It is now known that oxidative stress represents one of the most important mechanisms in its pathophysiology, from the early stages to the terminal phase. Oxidation increases inflammation and reduces the capacity of NO• to relax vascular smooth muscle, in part by decreasing bioavailability of tetrahydrobiopterin (BH4), leading to endothelial dysfunction and high blood pressure, and due to the limited effectiveness of existing treatments, new drugs are needed to prevent and/or treat these mechanisms. The aim of this study was to test apocynin in a 5/6 nephrectomy mouse model of CKD to investigate whether its known antioxidant effect can improve the disease outcome. This effect results from the inhibition of NADPH oxidase and consequently a reduced production of the superoxide anion (O2•-). Animals were divided into five groups: sham, 5/6 nephrectomy only, and 5/6 nephrectomy followed by treatment with captopril, losartan or apocynin. The parameters evaluated were blood pressure and markers of oxidative stress (O2•-) and endothelial function (BH4). There were significantly lower levels of and a greater availability of serum BH4 in the apocynin-treated animals versus the control group and the two other drug treatments. The present findings suggest that apocynin in conjunction with a coadjuvant for modulating blood pressure may be useful for controlling the progression of CRF.
AB - A worldwide public health problem is chronic kidney disease (CKD) presenting alarming epidemiological data. It currently affects about 10% of the adult population worldwide and has a high mortality rate. It is now known that oxidative stress represents one of the most important mechanisms in its pathophysiology, from the early stages to the terminal phase. Oxidation increases inflammation and reduces the capacity of NO• to relax vascular smooth muscle, in part by decreasing bioavailability of tetrahydrobiopterin (BH4), leading to endothelial dysfunction and high blood pressure, and due to the limited effectiveness of existing treatments, new drugs are needed to prevent and/or treat these mechanisms. The aim of this study was to test apocynin in a 5/6 nephrectomy mouse model of CKD to investigate whether its known antioxidant effect can improve the disease outcome. This effect results from the inhibition of NADPH oxidase and consequently a reduced production of the superoxide anion (O2•-). Animals were divided into five groups: sham, 5/6 nephrectomy only, and 5/6 nephrectomy followed by treatment with captopril, losartan or apocynin. The parameters evaluated were blood pressure and markers of oxidative stress (O2•-) and endothelial function (BH4). There were significantly lower levels of and a greater availability of serum BH4 in the apocynin-treated animals versus the control group and the two other drug treatments. The present findings suggest that apocynin in conjunction with a coadjuvant for modulating blood pressure may be useful for controlling the progression of CRF.
KW - Apocynin
KW - Chronic renal failure
KW - Endothelial dysfunction
KW - Nephrectomy
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=85044161103&partnerID=8YFLogxK
U2 - 10.1080/0886022X.2017.1421557
DO - 10.1080/0886022X.2017.1421557
M3 - Artículo
C2 - 29299955
SN - 0886-022X
VL - 40
SP - 92
EP - 98
JO - Renal Failure
JF - Renal Failure
IS - 1
ER -