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Indian J Pharmacol. 2013 Mar-Apr;45(2):149-54. doi: 10.4103/0253-7613.108297.

Nimodipine inhibits N-methyl-N-nitrosourea-induced retinal photoreceptor apoptosis in vivo.

Author information

1
Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang- 110 001, People's Republic of China.

Abstract

PURPOSE:

The purpose of the present study was to investigate the effect of nimodipine (NMD), a calcium channel blocker, on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration.

MATERIALS AND METHODS:

60 mg/kg MNU was given intraperitoneally to 6-week-old female Sprague-Dawley rats, and NMD was injected intraperitoneally for up to 5 days after MNU. The effect of NMD was evaluated by electron microscopy and electroretinography (ERG). Proteins of Bax, Bcl-2, Caspase-3, and mitochondrial membrane potential (MMP) were analyzed with flow cytometry. The expressions of phosphodiesterase (PDE) and Caspase-3 were detected by reverse transcriptase polymerase chain reaction (RT-PCR).

RESULTS:

The apparent preservation of NMD to the photoreceptor cell was demonstrated by electron microscopy. After NMD treatment, both a- and b-waves of ERG were significantly higher compared with the control group, and had a protective effect on MNU-damaged retinal ERG. Flow cytometric assays showed that NMD decreased the level of Bax and Caspase-3 and increased the activity of Bcl-2 in retina. NMD significantly restored the mitochondrial membrane potential (MMP). RT-PCR analysis demonstrated that NMD treatment significantly decreased mRNA level of Caspase-3, and mRNA level of PDE was clearly upregulated.

CONCLUSIONS:

These data suggest that NMD may regulate the expressions of Bax, Bcl-2, Caspases-3, and PDE, and protection on the functions of retinal cell mitochondria inhibit MNU-induced photoreceptor cell apoptosis and protect retinal function in rats.

KEYWORDS:

N-methyl-N-nitrosourea; Nimodipine; retinal degeneration

PMID:
23716891
PMCID:
PMC3660927
DOI:
10.4103/0253-7613.108297
[Indexed for MEDLINE]
Free PMC Article
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