Tetramethylpyrazine protected photoreceptor cells of rats by modulating nuclear translocation of NF-kappaB1

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 factorkappa B (NF-κB) 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-κB 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 timedependently upregulated the NF-κB/p65 protein level in the nucleus and downregulated the IκBα 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. Key wordst e t r a m e t h y l p y r a z i n e ; p h o t o r e c e p t o r s ; methylnitrosourea; apoptosis; NF-kappa B;

Protective effects of tetramethylpyrazine on rat retinal cell cultures

“…Accumulating evidence suggests that the cytoprotective effect of TMP might be mediated by its antioxidant potentialities in cells (Shih et al, 2002;Zhang et al, 2003;Yang et al, 2005). In agreement with these observations, we detected a strong protective effect of TMP on retinal cells against ROS generator, H 2 O 2 , -induced cytotoxicity.…”

“…Improvements of learning and cognitive function by TMP were also reported in rodents following D-galactose-or arterial occlusion-induced brain lesions (Ni et al, 1995;Zhang et al, 2004). In addition, TMP protects photoreceptor from drug-induced damage as well as optic nerve axon lesions caused by intraocular hypertension (Li et al, 2000;Yang et al, 2005). Despite accumulating reports showing the cytoprotective effects of TMP, the pharmacological mechanism of TMP for neuroprotection is still poorly understood at the molecular level.…”

Tetramethylpyrazine Attenuates Transdifferentiation of TGF-β2–Treated Human Tenon's Fibroblasts

“…19,20 Accumulating evidence suggests that TMP may have therapeutic potential as a complementary therapy for various ocular diseases, including vascular retinopathy, corneal neovascularization, optic neuropathy, and glaucoma. 16,[21][22][23] In particular, our latest investigation implicated TMP in attenuation of TGF-b-induced pathologic changes in trabecular meshwork cells, showing that it inhibits cytoskeleton remodeling and ECM accumulation through the SDF/CXCR4 axis. 24 Prompted by these previous reports, we sought to characterize the bioactivity of TMP and its underlying mechanism.…”

Tetramethylpyrazine attenuates PPAR-γ antagonist-deteriorated oxazolone-induced colitis in mice

“…Recently, the pharmacological effects of TMP have been expanded from its well-known vasodilatory actions and antiplatelet activity to a wide variety of activities such as anti-inflammatory, anti-stress [tetramethylpyrazine protects against palmitate-induced oxidative damage and mitochondrial dysfunction in C2C12 myotubes (16)], and antiapoptosis activity. TMP can protect against MNU-induced retinal damage (17), iron-induced oxidative damage and apoptosis in cerebellar granule cells (18), gastric mucosal injury in a rat model of acute necrotizing pancreatitis, spinal cord ischemia, gentamicin-induced apoptosis in murine renal tubular cells (19), rat asthma, acute liver and lung injury after burn trauma (20), acute myocardium injury after thermal trauma (21) and accelerated anti-glomerular basement membrane antibody nephritis (22). Several studies have also reported that one of the underlying mechanisms of TMP is its reactive oxygen species (ROS)-scavenging activity (21)(22)(23)(24).…”