Tetramethylpyrazine protected photoreceptor cells of rats by modulating nuclear translocation of NF-kappaB

Acta Pharmacol Sin. 2005 Jul;26(7):887-92. doi: 10.1111/j.1745-7254.2005.00141.x.

Abstract

Aim: To evaluate the effect of tetramethylpyrazine (TMP) injection on retinal damage induced by N-methyl-N-nitrosourea (MNU) in rats and on nuclear factor-kappa B (NF-kappaB) family members.

Methods: Female Sprague-Dawley (SD) rats were randomly divided into groups: (i), control group; (ii), model group; and (iii), TMP-injection groups, in which the rats were subdivided into 40 mg/kg, 80 mg/kg and 160 mg/kg groups. Drugs were injected ip into 47-day-old SD rats once a day. At 50 days of age, all rats in the model group and drug groups also received a single ip injection of 60 mg/kg MNU. Rats in group 1 received ip injection of physiological saline. All rats were killed at different times after MNU or physiological saline treatment. The apoptotic index of photoreceptor cells was calculated by TUNEL labeling; retinal damage was evaluated based on retinal thickness and the expression of NF-kappaB family members was detected by Western blot.

Results: TMP injections, in a dose-dependent manner, suppressed photoreceptor cell apoptosis and decreased its loss in the peripheral retina. As compared with the MNU-treated group, TMP injection at a dose of 160 mg/kg also time-dependently upregulated the NF-kappaB/p65 protein level in the nucleus and downregulated the IkappaBalpha protein level in the cytoplasm. However, no protective effect of TMP injection on MNU-induced central retinal damage was found.

Conclusion: TMP injection partially protects against MNU-induced retinal damage by upregulating the nuclear translocation of p65 to inhibit photoreceptor cells apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Nucleus / metabolism*
  • Cytoplasm / metabolism
  • Female
  • I-kappa B Proteins / metabolism
  • Ligusticum / chemistry
  • Methylnitrosourea
  • NF-KappaB Inhibitor alpha
  • Photoreceptor Cells, Vertebrate / metabolism
  • Photoreceptor Cells, Vertebrate / pathology*
  • Plants, Medicinal / chemistry
  • Pyrazines / isolation & purification
  • Pyrazines / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Diseases / chemically induced
  • Retinal Diseases / pathology
  • Transcription Factor RelA / metabolism*

Substances

  • I-kappa B Proteins
  • Nfkbia protein, rat
  • Pyrazines
  • Transcription Factor RelA
  • NF-KappaB Inhibitor alpha
  • Methylnitrosourea
  • tetramethylpyrazine