Targeting mitochondria with folic acid and vitamin B12 ameliorates nicotine mediated islet cell dysfunction

Nicotine, one of the well‐known highly toxic components of cigarette smoke, causes a number of adverse health effects and diseases. Our previous study has shown that nicotine induces reactive oxygen species (ROS) in islet cell and disrupts islet cell mitochondrial membrane potential (ΔΨm). However, supplementation with folic acid and vitamin B₁₂ were found effective against nicotine induced changes in pancreatic islet cells. But the toxicological effects and underlying mechanisms of nicotine‐induced mitochondrial dysfunction is still unknown. In this study, nicotine exposure decreases mitochondrial enzymes (pyruvate dehydrogenase, alpha‐ketoglutarate dehydrogenase, aconitase, malate dehydrogenase) activities by increasing cytosolic Ca²⁺ level which may contribute to increased mitochondrial ROS production by raising its flow to mitochondria. This in turn produces malondialdehyde and nitric oxide (NO) with a concomitant decrease in the activities of antioxidative enzymes and glutathione levels leading to loss of ΔΨm. Simultaneously, nicotine induces pancreatic islet cell apoptosis by modulating ΔΨm via increased cytosolic Ca²⁺ level, altered Bcl‐2, Bax, cytochrome c, caspase‐9, PARP expressions which were prevented by the supplementation of folic acid and vitamin B₁₂. In conclusion, nicotine alters islet cell mitochondrial redox status, apoptotic machinery, and enzymes to cause disruption in the ΔΨm and supplementation of folic acid and vitamin B₁₂ possibly blunted all these mitochondrial alterations. Therefore, this study may help to determine the pathophysiology of nicotine‐mediated islet cell mitochondrial dysfunction.     

叶酸和维生素B12对糖尿病肾病患者氧化应激水平的影响

目的:探讨叶酸(FA)、维生素B1(2VitB12)干预对糖尿病肾病(DN)患者血浆同型半胱氨酸(Hcy)和氧化应激的影响,从而提供治疗DN的有效治疗方法。方法:将40例DN患者随机分为DN1组和DN2组,DN1组仅给予常规治疗,DN2组在常规治疗的基础上给予FA5mg和VitB12500μg每日3次,干预时间为2周。测定治疗前后的血糖、Hcy、FA、VitB12、血清丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)、肾功能、肝功能、总胆固醇(CHO)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、24h尿微量白蛋白。结果:(1)治疗后,DN1组FA、VitB12、Hcy无明显变化,DN2组FA、VitB12上升,Hcy水平下降(P<0.01),DN1组和DN2组血糖、MDA、24h尿微量白蛋白定量较干预前下降,NO、SOD较干预前升高(P<0.01)。(2)DN2组MDA、NO、SOD、24h尿微量白蛋白变化幅度高于DN1组(P<0.05)。结论:补充FA、VitB12可降低同型半胱氨酸,降低DN患者体内的氧化应激水平,可能是治疗DN的有效措施。     

正常人血浆中同型半胱氨酸水平及其与叶酸和维生素B12的相互关系

目的 :测定正常人血浆同型半胱氨酸 (HCY)、血清叶酸和维生素B12 水平 ,以探讨不同年龄组 3者之间的相互关系。方法 :用HPLC法测定血浆HCY水平 ,放射免疫法测定血清叶酸及维生素B12 水平。结果 :2 4 7例正常人血浆HCY水平、血清叶酸和维生素B12 水平分别为 (8 8± 2 4 ) μmol·L-1,(5 93± 2 31)ng·mL-1和 (9 3± 3 2 )ng·mL-1。血浆HCY水平随年龄增加呈明显升高 (r=0 5 4 2 0 ,P <0 0 1) ,6 1～ 70a正常老年人的血浆HCY水平为 (11 5± 2 2 ) μmol·L-1,较其他各年龄组有非常显著差别(P均 <0 0 1)。同时 ,血清叶酸和维生素B12 水平随年龄增加呈明显降低 ,与HCY水平呈负相关 (r=- 0 3891和 - 0 2 80 1,P<0 0 1)。结论 :正常人血浆HCY水平随年龄增加而明显升高 ,并与叶酸和维生素B12 水平呈负相关。     

不同剂量叶酸联合维生素B12干预对高Hcy急性心肌梗死患者预后的影响

目的：探讨不同剂量叶酸联合维生素B12干预对高同型半胱氨酸（HHcy）急性心肌梗死患者预后的影响。方法：445例HHcy急性心肌梗死患者按照治疗方法分为观察组（n=223）和对照组（n=222）。比较两组患者治疗前后血清Hcy水平,分析影响HHcy心肌梗死患者发生主要不良心血管事件（MACE）的相关因素。结果：治疗后两组患者血清Hcy水平均下降,观察组下降幅度高于对照组（P<0.05）。治疗后观察组2a MACE发生率明显低于对照组（9.87%vs 21.62%,P<0.05）。Cox单因素及多因素分析显示年龄、糖尿病、LDL-C、Hcy、治疗方式与HHcy急性心肌梗死患者治疗后发生MACE密切相关。结论：叶酸联合维生素B12干预能够降低HHcy急性心肌梗死患者MACE的发生率,且叶酸剂量15 mg·d^-1效果最佳。