Betaine (N,N,N-trimethylglycine) averts photochemically-induced thrombosis in pial microvesselsin vivoand platelet aggregationin vitro

Abstract

Betaine (N,N,N-trimethylglycine) is an important food component with established health benefits through its homocysteinelowering effects, and is used to lower total homocysteine concentration in plasma of patients with homocystinuria. It is well established that hyperhomocysteinemia is an established risk factor for cardiovascular disease and stroke. However, the possible protective effect of betaine on coagulation events in vivo and in vitro has thus far not been studied. Betaine was given to mice at oral doses of either 10 mg/kg (n ¼ 6) or 40 mg/kg (n ¼ 6) for seven consecutive days, and control mice (n ¼ 6) received water only. The thrombotic occlusion time in photochemically induced thrombosis in pial arterioles was significantly delayed in mice pretreated with betaine at doses of 10 mg/kg (P < 0.001) and 40 mg/kg (P < 0.01). Similar effects were observed in pial venules with 10 mg/kg (P < 0.05) and 40 mg/kg (P < 0.05) betaine. In vitro, in whole blood samples collected from untreated mice (n ¼ 3-5), betaine (0.01-1 mg/mL) significantly reversed platelet aggregation induced by adenosine diphosphate (5 mM). The number of circulating platelets and plasma concentration of fibrinogen in vivo were not significantly affected by betaine pretreament compared with the control group. Lipid peroxidation (LPO) in mice pretreated with betaine was significantly reduced compared with the control group. Moreover, betaine (0.01-1 mg/mL) caused a dose-dependent and significant prolongation of PT (n ¼ 5) and aPTT (n ¼ 4-6). In conclusion, our data show that betaine protected against coagulation events in vivo and in vitro and decreased LPO in plasma.Keywords: Betaine, platelets, thrombosis, mice, lipid peroxidation Experimental Biology and Medicine 2015; 240: 955-960.

Integrated analysis of the association between methionine cycle and risk of moyamoya disease

“…Betaine played an important role in reducing oxidative stress, inhibiting NF‐κB activity, and NLRP3 inflammasome activation, and attenuating endoplasmic reticulum stress and apoptosis 48 . Additionally, betaine has been shown to protect against coagulation events and reverse platelet aggregation 49 . Interestingly, there seemed to be a potential link between betaine and MetO.…”

“… 48 Additionally, betaine has been shown to protect against coagulation events and reverse platelet aggregation. 49 Interestingly, there seemed to be a potential link between betaine and MetO. A recent study has found that betaine could increase the expression of MetO reductases b1 (Msrb1) and b2 (Msrb2) to exert a neuroprotective effect in ischemia/reperfusion injury‐induced brain damage.…”

Circulating choline pathway nutrients and risk of moyamoya disease

“…Second, betaine inhibits nuclear factor-κB activity, and nod-like receptor protein 3 (NLRP3) inflammasome activation has anti-inflammatory effects ( 14 ). Additionally, experimental studies have shown that betaine could reverse platelet aggregation in vivo and in vitro and protect against coagulation events ( 32 ).…”

Water-Pipe Smoke Exposure-Induced Circulatory Disturbances in Mice, and the Influence of Betaine Supplementation Thereon

“…Experimental studies in rats have reported that betaine has a protective effect against ethanol-induced hepatic steatosis [21], CCl 4 -induced kidney injury [22] and ethanol-induced oxidative stress in testes [23]. A recent study in mice has shown that betaine averts photochemically induced thrombosis [24]. However, the possible alleviating effect of betaine on WPS-induced cardiovascular toxicity has, as far as we are aware, not been studied before.…”

“…(10 and 40 mg/kg) averted photochemically-induced thrombosis in pial microvessels in vivo [24]. Here, we assessed, probably for the first time, a more relevant way of administration of betaine.…”