Department of Oral and Maxillofacial Pathology, Saveetha Dental College, Chennai, India.
Arch Oral Biol. 2013 Jun;58(6):563-74. doi: 10.1016/j.archoralbio.2013.01.016. Epub 2013 Mar 8.
Ascorbic acid or Vitamin C is a potent dietary antioxidant with a double faced character, in that it exhibits a pro-oxidant activity arising from its routine antioxidant property that generates reactive free radicals, which induce cytotoxic effects at pharmacologic concentrations. A systematic review of this effect of ascorbic acid in the oral tumours and normal oral tissues would clearly elucidate the merits or demerits of employing vitamin C in treating the same.
The aim of our systematic review is to critically review the studies reported in literature that have studied the pro-oxidant activity of ascorbic acid as a therapeutic option for treatment of oral neoplasms and its effects on normal oral cells.
Articles were searched in PUBMED, MEDLINE using appropriate key words like "ascorbic acid", "pro-oxidant activity", "treatment", "oral neoplasms". Hand search of Journals was also performed. Articles were reviewed and analysed.
The search strategy included 17 potentially relevant articles for review of which, 12 were in vitro studies; 3 were in vivo animal studies; 1 was in vivo human study and 1 was ex vivo human study. The optimum concentration of ascorbic acid used to produce potential pro-oxidant associated cytotoxic effects was found to be 3-5mM in vitro, 0.88-5mM in vivo animals, 0.5-2mM ex vivo in humans, and the corresponding effects are induction of apoptosis (caspase activation), necrosis, free radical formation, H2O2 generation, and DNA fragmentation. In contrast, the same pro-oxidant concentrations had no effect on the normal cells.
The results of our systematic review show that the pro-oxidant activity of pharmacologic ascorbic acid is a part of its dose-dependent bimodal activity and is a result of the proposed Fenton mechanism. In vitro, animal and ex vivo studies of pharmacologic ascorbic acid (AA) have yielded meritorious results proving vitamin C as an effective cytotoxic agent against oral neoplastic cells with potentially no harming effects on normal cells. However, a shortage of clinical trials and in vivo human studies pertaining to evaluation of anti-tumour activity of vitamin C in tumours of oral cavity remains a lacuna in concluding ascorbic acid as a beneficial therapeutic option in treatment of oral neoplasms.
抗坏血酸或维生素 C 是一种具有双重特性的强效膳食抗氧化剂，它表现出一种源自其常规抗氧化特性的促氧化剂活性，即生成活性自由基，在药理浓度下会引起细胞毒性作用。系统评价抗坏血酸在口腔肿瘤和正常口腔组织中的这种作用，将清楚地阐明在治疗口腔肿瘤时使用维生素 C 的优点或缺点。
我们系统评价的目的是批判性地评价文献中报道的研究，这些研究探讨了抗坏血酸作为治疗口腔肿瘤的治疗选择的促氧化剂活性，以及它对正常口腔细胞的影响。
在 PUBMED、MEDLINE 中使用适当的关键词搜索文章，如“抗坏血酸”、“促氧化剂活性”、“治疗”、“口腔肿瘤”。还进行了期刊的手工搜索。对文章进行了回顾和分析。
搜索策略包括 17 篇有潜力的相关文章进行综述，其中 12 篇为体外研究；3 篇为体内动物研究；1 篇为体内人类研究；1 篇为体外人类研究。发现产生潜在促氧化剂相关细胞毒性作用的最佳抗坏血酸浓度为体外 3-5mM，体内动物 0.88-5mM，体外人类 0.5-2mM，相应的作用是诱导细胞凋亡（半胱天冬酶激活）、坏死、自由基形成、H2O2 生成和 DNA 片段化。相比之下，相同的促氧化剂浓度对正常细胞没有影响。
我们的系统评价结果表明，药理抗坏血酸的促氧化剂活性是其剂量依赖性双模态活性的一部分，是 Fenton 机制的结果。体外、动物和体外人类的药理抗坏血酸（AA）研究取得了有价值的结果，证明维生素 C 是一种有效的细胞毒性剂，对口腔肿瘤细胞有效，而对正常细胞没有潜在的伤害作用。然而，缺乏关于维生素 C 在口腔肿瘤中的抗肿瘤活性的临床试验和体内人类研究，仍然是在结论中认为抗坏血酸是治疗口腔肿瘤的有益治疗选择的一个空白。
