Tetrahydrobiopterin (bh4) supplementation prevents the cardiorenal effects of diabetes in mice by reducing oxidative stress, inflammation and fibrosis
Autor
Novoa, Ulises
Soto, Karen
Valdés, Cristian
Villaseñor, Jorge
Treuer, Adriana V.
González, Daniel R.
Fecha
2022Resumen
Background: The effects of diabetes on the cardiovascular system as well as in the kidney
are profound, which include hypertrophy and fibrosis. Diabetes also induces oxidative stress, at least
in part due to the uncoupling of nitric oxide synthase (NOS); this is a shift in NO production toward
superoxide production due to reduced levels of the NOS cofactor tetrahydrobiopterin (BH4). With
this in mind, we tested the hypothesis that BH4 supplementation may prevent the development of
diabetic cardiomyopathy and nephropathy. Methods: Diabetes was induced in Balb/c mice with
streptozotocin. Then, diabetic mice were divided into two groups: one group provided with BH4
(sapropterin) in drinking water (daily doses of 15 mg/kg/day, during eight weeks) and the other
that received only water. A third group of normoglycemic mice that received only water were used
as the control. Results: Cardiac levels of BH4 were increased in mice treated with BH4
(p = 0.0019). Diabetes induced cardiac hypertrophy, which was prevented in the group that received BH4
(p < 0.05). In addition, hypertrophy was evaluated as cardiomyocyte cross-sectional area. This was reduced
in diabetic mice that received BH4 (p = 0.0012). Diabetes induced cardiac interstitial fibrosis that
was reduced in mice that received BH4 treatment (p < 0.05). We also evaluated in the kidney the
impact of BH4 treatment on glomerular morphology. Diabetes induced glomerular hypertrophy
compared with normoglycemic mice and was prevented by BH4
treatment. In addition, diabetic mice presented glomerular fibrosis, which was prevented in mice that received BH4 . Conclusions: These results suggest that chronic treatment with BH4
in mice ameliorates the cardiorenal effects of diabetes,, probably by restoring the nitroso–redox balance. This offers a possible new alternative to explore a BH4-based treatment for the organ damage caused by diabetes.
Fuente
Biomedicines, 10(10), 2479Link de Acceso
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doi.org/10.3390/biomedicines10102479Colecciones
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