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脂质体镁原卟啉在半乳糖喂养大鼠中抗白内障作用的机制

Mechanism of the anticataract effect of liposomal MgT in galactose-fed rats.

作者信息

Iezhitsa Igor, Agarwal Renu, Saad Sarah Diyana Bt, Zakaria Fatin Kamilah Bt, Agarwal Puneet, Krasilnikova Anna, Rahman Thuhairah Hasrah Abdul, Rozali Khairul Nizam Bin, Spasov Alexander, Ozerov Alexander, Alyautdin Renad, Ismail Nafeeza Mohd

机构信息

Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor Darul Ehsan, Selangor, Malaysia; Universiti Teknologi MARA, RIG "Molecular Pharmacology and Advanced Therapeutics," Pharmaceutical & Life Sciences (PLS) Communities of Research (CoRe), Shah Alam, Selangor Darul Ehsan, Malaysia; Volgograd State Medical University, Research Institute of Pharmacology, 1 Pavshikh Bortsov sq., Volgograd, Russian Federation.

Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor Darul Ehsan, Selangor, Malaysia; Universiti Teknologi MARA, RIG "Molecular Pharmacology and Advanced Therapeutics," Pharmaceutical & Life Sciences (PLS) Communities of Research (CoRe), Shah Alam, Selangor Darul Ehsan, Malaysia.

出版信息

Mol Vis. 2016 Jul 10;22:734-47. eCollection 2016.

PMID:27440992
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4942261/
Abstract

PURPOSE

Increased lenticular oxidative stress and altered calcium/magnesium (Ca/Mg) homeostasis underlie cataractogenesis. We developed a liposomal formulation of magnesium taurate (MgT) and studied its effects on Ca/Mg homeostasis and lenticular oxidative and nitrosative stress in galactose-fed rats.

METHODS

The galactose-fed rats were topically treated with liposomal MgT (LMgT), liposomal taurine (LTau), or corresponding vehicles twice daily for 28 days with weekly anterior segment imaging. At the end of the experimental period, the lenses were removed and subjected to analysis for oxidative and nitrosative stress, Ca and Mg levels, ATP content, Ca(2+)-ATPase, Na(+),K(+)-ATPase, and calpain II activities.

RESULTS

The LTau and LMgT groups showed significantly lower opacity index values at all time points compared to the corresponding vehicle groups (p<0.001). However, the opacity index in the LMgT group was lower than that in the LTau group (p<0.05). Significantly reduced oxidative and nitrosative stress was observed in the LTau and LMgT groups. The lens Ca/Mg ratio in LMgT group was decreased by 1.15 times compared to that in the LVh group. Calpain II activity in the LMgT group was decreased by 13% compared to the LVh group. The ATP level and Na(+),K(+)-ATPase and Ca(2+)-ATPase activities were significantly increased in the LMgT group compared to the LVh group (p<0.05).

CONCLUSIONS

Topical liposomal MgT delays cataractogenesis in galactose-fed rats by maintaining the lens mineral homeostasis and reducing lenticular oxidative and nitrosative stress.

摘要

目的

晶状体氧化应激增加和钙/镁(Ca/Mg)稳态改变是白内障发生的基础。我们开发了一种牛磺酸镁(MgT)脂质体制剂,并研究了其对半乳糖喂养大鼠Ca/Mg稳态以及晶状体氧化和亚硝化应激的影响。

方法

对半乳糖喂养的大鼠每日两次局部给予脂质体MgT(LMgT)、脂质体牛磺酸(LTau)或相应载体,持续28天,并每周进行前节成像。实验期结束时,取出晶状体并进行氧化和亚硝化应激、Ca和Mg水平、ATP含量、Ca(2+)-ATP酶、Na(+),K(+)-ATP酶以及钙蛋白酶II活性分析。

结果

与相应载体组相比,LTau组和LMgT组在所有时间点的混浊指数值均显著降低(p<0.001)。然而,LMgT组的混浊指数低于LTau组(p<0.05)。LTau组和LMgT组的氧化和亚硝化应激明显降低。与载体组相比,LMgT组晶状体的Ca/Mg比值降低了1.15倍。与载体组相比,LMgT组的钙蛋白酶II活性降低了13%。与载体组相比,LMgT组的ATP水平以及Na(+),K(+)-ATP酶和Ca(2+)-ATP酶活性显著增加(p<0.05)。

结论

局部应用脂质体MgT可通过维持晶状体矿物质稳态并降低晶状体氧化和亚硝化应激来延缓半乳糖喂养大鼠的白内障形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51e1/4942261/eaa95740a4da/mv-v22-734-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51e1/4942261/9d3b0d8f57f8/mv-v22-734-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51e1/4942261/69019d2d3263/mv-v22-734-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51e1/4942261/694c18b94222/mv-v22-734-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51e1/4942261/eaa95740a4da/mv-v22-734-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51e1/4942261/9d3b0d8f57f8/mv-v22-734-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51e1/4942261/69019d2d3263/mv-v22-734-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51e1/4942261/694c18b94222/mv-v22-734-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51e1/4942261/eaa95740a4da/mv-v22-734-f4.jpg

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