Long-term methionine-diet induced mild hyperhomocysteinemia associated cardiac metabolic dysfunction in multiparous rats

Abstract

Mild hyperhomocysteinemia (HHcy, clinically defined as less than 30 μmol/L) is an independent cardiovascular disease (CVD) risk factor, and is associated with many complications during pregnancy, such as preeclampsia (PE). The aim of this study was to assess the effect of long-term mild HHcy on cardiac metabolic function of multiparous rats. Female rats were mated 3 to 4 times and were fed with methionine in drinking water to increase plasma Hcy (2.9 ± 0.3 to 10.5 ± 2.3 μmol/L) until termination. This caused significant increase of heart weight/body weight (0.24 ± 0.01 to 0.27 ± 0.01 g/100 g) and left ventricle weight (0.69 ± 0.03 to 0.78 ± 0.01 g). Superoxide production was increased by 2.5-fold in HHcy hearts using lucigenin chemiluminescence. The ability of bradykinin and carbachol to regulate myocardial oxygen consumption (MVO2) in vitro was impaired by 59% and 66% in HHcy heart, and it was restored by ascorbic acid (AA), tempol, or apocynin (Apo). Protein expression of p22phox subunit of NAD(P)H oxidase was increased by 2.6-fold, but there were no changes in other NAD(P)H oxidase subunits, NOSs or SODs. Microarray revealed 1518 genes to be differentially regulated (P < 0.05). The mRNA level of NAD(P)H oxidase subunits, NOSs or SODs remained unchanged. In conclusion, long-term mild HHcy increases cardiac superoxide mainly through regulation of p22phox component of the NAD(P)H oxidase and impairs the ability of NO to regulate MVO2 in heart of multiparous mothers.

Divergent outcomes of fructose consumption on exercise capacity of rats: friend or foe

“…8A). In agreement with previous studies (33,34,43), administration of BK to normal hearts stimulated NO release to suppress oxygen consumption, a response that spares oxygen to potentiate exercise tolerance. However, the BK-induced NO-mediated suppression of MV O 2 was basically indiscernible in myocardium of rats in the HF- 30D group (Fig.…”

Effect of Methionine Diet on Time-Related Metabolic and Histopathological Changes of Rat Hippocampus in the Model of Global Brain Ischemia

“…If the plasma levels of Hcy exceed 10–15 μmol/l, there is a condition known as hHcy, which occurs as a result of an inborn error of methionine metabolism or by non-genetic causes [ 35 ]. In our experiment, in the Met-C group was the level of Hcy increased 1.5-fold in comparison to the naïve control animals that matches the criteria for mild hHcy [ 35 , 36 ]. Dos Santos et al [ 37 ] demonstrated in their hHcy model (subcutaneous injection of DL-Hcy in the lower dose of 0.03 μmol/g of the body weight of male Wistar rats twice a day for 30 days that this dose increases rats Hcy plasma concentration, similarly described in the moderate hHcy patients.…”

The Role of Methionine-Rich Diet in Unhealthy Cerebrovascular and Brain Aging: Mechanisms and Implications for Cognitive Impairment

“…High methionine intake and/or hyperhomocysteinemia have also been shown to upregulate major cellular oxidant systems, including NAD(P)H oxidases [90-95]. NAD(P)H oxidases, also known as NOX enzymes, are a family of enzymes contributing to age-related increases in ROS production in cells of the cardiovascular and immune systems as well as other organs [93, 165,166]. In the context of high methionine intake and hyperhomocysteinemia, increased NAD(P)H oxidase activity can further exacerbate age-related oxidative stress [93,165].…”