N-alpha-acetylcarnosine is a prodrug of L-Carnosine in ophthalmic application as antioxidant
N-alpha-acetylcarnosine is a prodrug of L-Carnosine in ophthalmic application as antioxidant
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DOI：
10.1016/0009-8981(96)06356-5
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发表时间：
1996-10-15
影响因子：
5
通讯作者：
Zheltukhina, GA
中科院分区：
文献类型：
--
作者：
Babizhayev, MA;Yermakova, VN;Zheltukhina, GA
天然化合物N-α-乙酰肌肽(NAG)被认为是L-肌肽(C)的前药，可抵抗人血清肌肽酶的酶解。用1%NAC、C或安慰剂处理兔眼，用反相高效液相、高效液相色谱法、薄层层析和离子交换层析技术分析前房房水提取物中咪唑类药物的含量。兔眼局部注射纯C不会导致这种化合物在房水中积聚超过30分钟，浓度超过安慰剂治疗的配对眼。NAC在从角膜到房水的过程中表现出剂量依赖性的降解，在一系列治疗方案中，眼内给药15-30分钟后释放C：小于或等于结膜下注射小于或等于超声诱导的凝胶。不同的治疗技术对1%NAC的眼部耐受性良好。一旦进入房水，C可能作为抗氧化剂进入晶状体组织，当存在有效浓度(5-15 mmoL/L)时。眼用前体药物NAC及其生物活性原理C作为通用抗氧化剂的优势与它们在生物膜的脂类相和水环境中提供有效的氧化应激保护的能力有关。NAC被建议用于治疗在其发生过程中含有氧化应激成分的眼部疾病(白内障、青光眼、视网膜变性、角膜疾病、眼部炎症、糖尿病并发症)。系统性疾病)。
The naturally occurring compound N-alpha-acetylcarnosine (NAG) is proposed as the prodrug of L-carnosine (C) resistant to enzymatic hydrolysis by human serum carnosinase. Rabbit eyes were treated with 1% NAC, C or placebo and extracts of the aqueous humor from the anterior eye chamber were analyzed for imidazole content by reverse phase analytical high performance liquid, chromatography (HPLC), thin-layer (TLC) and ion-exchange chromatographic techniques. The topical administration of pure C to the rabbit eye did not lead to accumulation of this compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eye. NAC showed dose-dependent hydrolysis in its passage from the cornea to the aqueous humor, releasing C after 15-30 min of ocular administration of prodrug in a series of therapeutical modalities: instillation less than or equal to subconjunctival injection less than or equal to ultrasound induced phoresis. Different treatment techniques showed excellent toleration of 1% NAC by the eye. Once in the aqueous humor, C might act as an antioxidant and enter the lens tissue when present at effective concentrations (5-15 mmol/l). The advantage of the ophthalmic prodrug NAC and its bioactivated principle C as universal antioxidants relates to their ability to give efficient protection against oxidative stress both in the lipid phase of biological membranes and in an aqueous environment. NAC is proposed to treat ocular disorders which have the component of oxidative stress in their genesis (cataracts, glaucoma, retinal degeneration, corneal disorders, ocular inflammation, complications of diabetes mellitus. systemic diseases).