靶向 CYP450 调节以降低实验模型中诱导性白内障的风险。

Targeting CYP450 modulation to decrease the risk of induced cataract in the experimental model.

机构信息

Department of Pharmacology, Anand Pharmacy College, SPU, Anand, India.

出版信息

Indian J Ophthalmol. 2010 Nov-Dec;58(6):471-5. doi: 10.4103/0301-4738.71676.

DOI:10.4103/0301-4738.71676

PMID:20952829

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2993975/

Abstract

BACKGROUND

Diabetes is one of the major causes of cataract. Some drugs prescribed for the treatment of diabetes are the modulators of CYP450, which may alter the risk of cataract.

OBJECTIVE

To study the effect of CYP450 modulation in galactosemic cataract.

MATERIALS AND METHODS

Male Sprague-Dawley suckling rats were allotted to four groups (n = 6), as follows: Group 1: Normal control, Group 2: Galactose control, Group 3: CYP450 inhibitor pretreated and Group 4: CYP450 inducer pretreated. Cataract was induced in animals of all groups except group 1 by feeding them galactose (50%), 21 days after parturition. From the eighteenth day of life, CYP450 inhibitor (nifedipine; 8.1 mg/kg) and CYP450 inducer (pioglitazone; 3.8 mg/kg) were given orally to groups 3 and 4, respectively. The maturation pattern of the cataract was observed by an operating microscope, every third day. Biochemical changes in the lenses of all groups, for example, CYP450 activity expressed as ΅M NADPH oxidized / unit time, alterations in the levels of total proteins, soluble proteins, and reduced glutathione (GSH) following the induction of cataract, were estimated.

RESULTS

The microscopic examination of the lenses indicated that CYP450 inhibitor pre-treatment delayed (fourteenth day) the occurrence of cataract, while CYP450 inducer pretreatment demonstrated an early (ninth day) cataract as compared to galactose control rats (twelfth day). A significant decrease and increase in CYP450 activity was observed with the CYP450 inhibitor and inducer pre-treatment, respectively. There was no alteration in the GSH level, but a significant increase in total and soluble protein was found in groups 3 and 4 as compared to group 2.

CONCLUSION

CYP450 may have a role in the initiation of cataract without any effect on the maturation pattern, as revealed by the delayed occurrence of cataract with the CYP450 inhibitor and an early onset of cataract with the CYP450 inducer.

摘要

背景

糖尿病是白内障的主要病因之一。一些用于治疗糖尿病的药物是 CYP450 的调节剂，可能会改变白内障的风险。

目的

研究 CYP450 调节对半乳糖性白内障的影响。

材料和方法

雄性 Sprague-Dawley 幼鼠被分为四组（n = 6），如下所示：第 1 组：正常对照组；第 2 组：半乳糖对照组；第 3 组：CYP450 抑制剂预处理组；第 4 组：CYP450 诱导剂预处理组。除第 1 组外，所有组的动物在产后第 21 天通过喂食半乳糖（50%）诱导白内障。从第 18 天开始，第 3 组和第 4 组分别口服 CYP450 抑制剂（硝苯地平；8.1 mg/kg）和 CYP450 诱导剂（吡格列酮；3.8 mg/kg）。每天用手术显微镜观察白内障的成熟模式。评估各组晶状体的生化变化，例如，CYP450 活性表示为 ΅M NADPH 氧化/单位时间，总蛋白、可溶性蛋白和还原型谷胱甘肽（GSH）水平在白内障诱导后的变化。

结果

晶状体的显微镜检查表明，CYP450 抑制剂预处理延迟（第 14 天）白内障的发生，而 CYP450 诱导剂预处理则与半乳糖对照组大鼠（第 12 天）相比表现为早期（第 9 天）白内障。CYP450 抑制剂和诱导剂预处理分别观察到 CYP450 活性显著降低和增加。与第 2 组相比，第 3 组和第 4 组的 GSH 水平没有改变，但总蛋白和可溶性蛋白水平显著增加。