cobrotoxin and Disease-Models--Animal

Topics: Acetylcholine; Animals; Autoimmune Diseases; Cobra Neurotoxin Proteins; Disease Models, Animal; Humans; Membrane Potentials; Motor Endplate; Myasthenia Gravis; Rats; Receptors, Cholinergic; Synaptic Transmission

The Naja atra (Chinese cobra), primarily distributing in the low or medium altitude areas of southern China and Taiwan, was considered as a medicine in traditional Chinese medicine and used to treat pain, inflammation and arthritis.. To study the anti-inflammatory and anti-arthritic activities of cobrotoxin (CTX), an active component of the venom from Naja atra.. Adjuvant-induced arthritis (AA) rats were used as the animal model of rheumatoid arthritis. The anti-arthritic effects of CTX were evaluated through the arthritis score, paw edema and histopathology changes of joints. The anti-inflammation effects were assayed by the level of IL-6, TNF-α, IL-1β and the number of inflammatory cells in peripheral blood, as well as the proliferation of fibroblast-like synoviocytes (FLS). The immune level was valued by the proliferation of T cells and the level of CD4 and CD8.. CTX alleviated the disease development of AA rats according to the ameliorating arthritis score, paw edema and histopathology character. At the meanwhile, CTX decreased the levels of IL-6, TNF-α, IL-1β and the numbers of inflammatory cells in peripheral blood. CTX also suppressed the abnormal increasing of CD4+ T cells/ CD8+ T cells ratio, and could significantly inhibit T cell proliferation. Consistent with its effects on inhibiting granuloma's formation, CTX inhibited the proliferation of the cultured FLSs. Further studies on inflammatory signaling in FLSs revealed that CTX could inhibit the NF-κB signaling pathway.. CTX has beneficial effects on rheumatoid arthritis by its immune regulation effects and anti-inflammation effects. The inhibition of NF-κB pathway partly contributes to the anti-inflammatory properties of CTX.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Proliferation; Cobra Neurotoxin Proteins; Disease Models, Animal; Edema; Elapid Venoms; Fibroblasts; Immunosuppression Therapy; Immunosuppressive Agents; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred ICR; NF-kappa B; Rats; Rats, Wistar; Signal Transduction; Synovial Membrane; Tumor Necrosis Factor-alpha

In this study we report that cobratoxin (CbTX), a long-chain postsynaptic α-neurotoxin isolated from the Thailand cobra, Naja naja kaouthia, has antinociceptive effect in rats with neuropathic pain. The neuropathic pain model was established in rats with partial sciatic nerve ligature (PSNL) method. The pain response was examined behaviorally with mechanical paw withdrawal and thermal paw withdrawal method. Different doses (0.56, 1.12 and 4.50 μg/kg) of CbTX were injected intrathecally. Injection of CbTX resulted in a significant dose-dependent antinociception as evidenced by increased mechanical withdrawal threshold and thermal withdrawal latency. CbTX also induces a significant dose-dependent inhibition of pain-evoked unit discharges of thalamic parafascicular neurons. Both the behavioral mechanical and thermal antinociception and the inhibition of pain-evoked discharges of neurons in thalamic parafascicular nucleus in PSNL model could be mimicked by PUN282987, selective α7 nicotinic AChR (α7 nAChR) agonist and reversed by methyllycaconitine (MLA) selective α7 nAChR antagonist. In summary, these results suggested that AChR α7 subunit was involved in the antinociceptive action of CbTX for neuropathic pain and might be the candidate target for analgesic drug design.

Topics: alpha7 Nicotinic Acetylcholine Receptor; Analgesics; Analysis of Variance; Animals; Cobra Neurotoxin Proteins; Disease Models, Animal; Injections, Spinal; Male; Neuralgia; Rats; Rats, Sprague-Dawley

Benefit and motor side effects of l-DOPA in Parkinson's disease have been related to dopamine transmission in the striatum. However, the putative involvement of serotonergic neurons in the dopaminergic effects of l-DOPA suggests that the striatum is not a preferential target of l-DOPA. By using microdialysis in a rat model of Parkinson's disease, we found that l-DOPA (3-100 mg/kg) increased dopamine extracellular levels monitored simultaneously in four brain regions receiving serotonergic innervation: striatum, substantia nigra, hippocampus, prefrontal cortex. The increase was regionally similar at the lowest dose and 2-3 times stronger in the striatum at higher doses. Citalopram, a serotonin reuptake blocker, or the destruction of serotonergic fibers by 5,7-dihydroxytryptamine impaired l-DOPA-induced dopamine release in all regions. These data demonstrate that l-DOPA induces an ectopic release of dopamine due to serotonergic neurons. The new pattern of dopamine transmission created by l-DOPA may contribute to the benefit and side effects of l-DOPA.

Topics: 5,7-Dihydroxytryptamine; Animals; Antiparkinson Agents; Brain; Citalopram; Cobra Neurotoxin Proteins; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Extracellular Fluid; Levodopa; Male; Microdialysis; Oxidopamine; Parkinsonian Disorders; Presynaptic Terminals; Raphe Nuclei; Rats; Selective Serotonin Reuptake Inhibitors; Serotonin; Sympatholytics; Synaptic Transmission

Neurological deficits in multiple sclerosis (MS) and in experimental allergic encephalomyelitis (EAE) show demyelination of the nerve fibers, which are responsible for transmission of signals. The myelin appears to be attacked by the cells of the immune system. A viral etiology has been implicated in patients with MS. Oxidized toxins (MN) have been shown over the past 50 years to act as antiviral agents that are capable of inhibiting viral replication, and have shown promise in alleviating symptoms in EAE models of MS. The safety of these compounds has been a factor in their limited use. Development of a modified cobra toxin (MCTX) may prove more beneficial in inhibiting symptoms of EAE. In this study a modified cobra toxin (MCTX) was compared with the older oxidized toxin (MN) in an established EAE animal model. The results show that MCTX is capable of inhibiting the development as well as the relapsing phase of EAE in Lewis rats more efficiently than MN. It is possible that a safe cobra toxin can be developed with therapeutic efficacy for treatment of MS or vaccine development.

Topics: Acute Disease; Animals; Cobra Neurotoxin Proteins; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Injections, Subcutaneous; Multiple Sclerosis; Rats; Rats, Inbred Lew; Secondary Prevention; Severity of Illness Index; Treatment Outcome