Klener Pavel, Scott Alexander Matthew, Cullen Joseph John, Stejskal Vera, Sliva Jiri, Kotlarova Lucie, Kostiuk Pavel, Prochazka Zdenek, Kucerova Marta
Charles University, Prague, Czech Republic.
Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
J Appl Biomed. 2020 Mar;18(1):1-7. doi: 10.32725/jab.2020.003. Epub 2020 Feb 19.
Health status is determined by the balance of oxidants and antioxidants which protects healthy cells against the threat of internal and external risk factors. Antioxidants such as ascorbate (vitamin C, ascorbic acid) are of fundamental importance in this respect. Ascorbate neutralizes potential damage caused by cellular oxidative stress which may be the greatest risk of damage to healthy tissue. Cellular oxidative stress is mediated by external factors (e.g. psychological stress, physical exertion, drugs, various diseases, environmental pollution, preservatives, smoking, and alcohol) and internal factors (products of cellular metabolism including reactive oxygen species). When the products of oxidative stress are not sufficiently neutralized, healthy cells are at risk for both mitochondrial and DNA damage. In the short term, cell function may deteriorate, while an increased production of proinflammatory cytokines over time may lead to the development of chronic inflammatory changes and diseases, including cancer. Although pharmaceutical research continues to bring effective chemotherapeutic agents to the market, a limiting factor is often the normal tissue and organ toxicity of these substances, which leads to oxidative stress on healthy tissue. There is increasing interest and imperative to protect healthy tissues from the negative effects of radio-chemotherapeutic treatment. The action of ascorbate against the development of oxidative stress may justify its use not only in the prevention of carcinogenesis, but as a part of supportive or complementary therapy during treatment. Ascorbate (particularly when administered parentally at high doses) may have antioxidant effects that work to protect healthy cells and improve patient tolerability to some toxic radio-chemotherapy regimens. Additionally, ascorbate has demonstrated an immunomodulatory effect by supporting mechanisms essential to anti-tumor immunity. Intravenous administration of gram doses of vitamin C produce high plasma levels immediately, but the levels drop rapidly. Following oral vitamin C administration, plasma levels increase slowly to relatively low values, and then gradually decay. With an oral liposomal formulation, significantly higher levels are attainable than with standard oral formulations. Therefore, oral administration of liposomal vitamin C appears to be an optimal adjunct to intravenous administration. In this review, the basic mechanisms and clinical benefits of ascorbate as an antioxidant that may be useful as complementary therapy to chemotherapeutic regimens will be discussed.
健康状况取决于氧化剂和抗氧化剂的平衡,这种平衡可保护健康细胞免受内部和外部风险因素的威胁。在这方面,抗氧化剂如抗坏血酸盐(维生素C、抗坏血酸)至关重要。抗坏血酸盐可中和细胞氧化应激造成的潜在损害,而细胞氧化应激可能是对健康组织造成损害的最大风险。细胞氧化应激由外部因素(如心理压力、体力消耗、药物、各种疾病、环境污染、防腐剂、吸烟和饮酒)和内部因素(包括活性氧在内的细胞代谢产物)介导。当氧化应激产物未得到充分中和时,健康细胞就有发生线粒体和DNA损伤的风险。短期内,细胞功能可能会恶化,而随着时间的推移促炎细胞因子产生增加可能会导致慢性炎症变化和疾病的发生,包括癌症。尽管药物研究不断将有效的化疗药物推向市场,但一个限制因素往往是这些物质对正常组织和器官的毒性,这会导致健康组织产生氧化应激。保护健康组织免受放化疗治疗的负面影响的兴趣日益增加且势在必行。抗坏血酸盐对氧化应激发展的作用可能证明其不仅可用于预防癌症发生,还可作为治疗期间支持性或补充性疗法的一部分。抗坏血酸盐(特别是高剂量静脉给药时)可能具有抗氧化作用,可保护健康细胞并提高患者对某些毒性放化疗方案的耐受性。此外,抗坏血酸盐通过支持抗肿瘤免疫所必需的机制已显示出免疫调节作用。静脉注射克剂量的维生素C可立即产生高血浆水平,但水平会迅速下降。口服维生素C后,血浆水平会缓慢上升至相对较低的值,然后逐渐下降。使用口服脂质体制剂时,可达到比标准口服制剂显著更高的水平。因此,口服脂质体维生素C似乎是静脉给药的最佳辅助手段。在本综述中,将讨论抗坏血酸盐作为抗氧化剂的基本机制和临床益处,其可能作为化疗方案的补充疗法发挥作用。