Moderate hyperhomocysteinemia provokes dysfunction of cardiovascular autonomic system and liver oxidative stress in rats

Abstract

Hyperhomocysteinemia (HHcy) is associated with cardiovascular disease, atherosclerosis and reactive oxygen species generation. Thus, our aim was to investigate whether there was an association between HHcy, blood pressure, autonomic control and liver oxidative stress. Male Wistar rats were divided into 2 groups and treated for 8weeks: one group (control, CO) received tap water, while the other group (methionine, ME) was given a 100mg/kg of methionine in water by gavage. Two catheters were implanted into the femoral artery and vein to record arterial pressure (AP) and heart rate (HR) and drug administration. Signals were recorded by a data acquisition system. Baroreflex sensitivity was evaluated by HR responses to AP changes induced by vasoactive drugs. HR variability and AP variability were performed by spectral analysis in time and frequency domains to evaluate the contribution of the sympathetic and parasympathetic modulation. Lipid peroxidation and antioxidant enzyme activities were evaluated by measuring superoxide dismutase, catalase and glutathione peroxidase in liver homogenates. The ME group presented a significant increase in systolic arterial pressure (118±9 vs 135±6mmHg), diastolic arterial pressure (81±6 vs. 92±4) and mean arterial pressure (95±7 vs. 106±6). In addition, pulse interval variability presented a significant decrease (41%), while the low frequency component of AP was significantly increased (delta P=6.24mmHg(2)) in the ME group. We also found a positive association between lipid peroxidation and cardiac sympathetic modulation, sympathetic and vagal modulation ratio and systolic pressure variability. Collectively, these findings showed that HHcy induced dysfunction of cardiovascular autonomic system and liver oxidative stress.

Vitamin B complex mitigates cardiac dysfunction in high‐methionine diet‐induced hyperhomocysteinemia

“…Hcy inhibits the activity of GSH in vitro and leads to a dramatic reduction of GSH. In conjunction with this reduction, other studies confirm that Hcy also significantly decreases the thiol redox state of vascular cells, as measured by the ratio of GSH/GSSG, through the oxidation of GSH . Superoxide dismutase is essential to catalyse the dismutation of superoxide and has been shown to protect cells from oxygen free radicals.…”

The role of homocysteine in seminal vesicles remodeling in rat

“…The pathological processes by which homocysteine promotes organ damage have yet not been fully elucidated. Oxidative stress [5] and activation of pro-inflammatory factors [6] have been proposed to explain the pathogenic effects of Hhcy. Previous studies have revealed that these processes induced by Hhcy were associated with initiation and progression of fibrosis characterized by an accumulation of extracellular matrix (ECM) proteins, particularly collagen and an imbalance of MMPs/TIMPs system, which also plays a determinant role in the regulation of collagen tissue turnover [7,8].…”

The effects of acute hyperhomocysteinemia induced by DL-homocysteine or DL-homocysteine thiolactone on serum biochemical parameters, plasma antioxidant enzyme and cardiac acetylcholinesterase activities in the rat

“…Disturbed fibrinogen levels may occur due to an established process of homocysteine vs proteins interactions. Recent studies have demonstrated that treatment with methionine for 8 weeks (100 mg/kg) led to liver dysfunction through increased ROS production [28].…”