Anti-inflammatory effects of Neurotoxin-Nna, a peptide separated from the venom of Naja naja atra

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Abstract

Background

Neurotoxin-Nna (NT), an analgesic peptide separated from the venom of Naja naja atra, has reported to have an exceptional specificity to block transmission of the nerve impulse by binding to the α- subunit of the nicotinic acetylcholine receptor in the membrane. However, little information is available on the anti-inflammatory effects of NT. Therefore, the anti-inflammatory activity of Neurotoxin-Nna was investigated in this study.

Methods

The anti-inflammatory effects of NT were evaluated by measuring its influence on several crucial factors in inflammatory pathways, including total antioxidant activity, antinociceptive effects in vivo, nuclear factor kappa B (NF-κB), polymorphonuclear cells (PMN), inducible nitric oxide synthase (iNOS), adhesion molecule (ICAM-1) and tactile hyperalgesia.

Results

NT treatment decreased the levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β). NT treatment decreased the total antioxidant status (TAOS) and reduced CFA-induced tactile hyperalgesia in a dose-dependent manner. NT significantly inhibited regulation of NF-kappaB activation and the production of IL-1β, TNF-α, iNOS and CAM-1. Moreover, NT suppressed infiltration of PMN.

Conclusions

Our results showed that NT reduced CFA-induced tactile hyperalgesia through inhibition inflammatory pathways in experimental inflammatory rats.

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Most cited references 17

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Fabien Marchand, Mauro Perretti, Stephen McMahon (2005)

During the past two decades, an important focus of pain research has been the study of chronic pain mechanisms, particularly the processes that lead to the abnormal sensitivity - spontaneous pain and hyperalgesia - that is associated with these states. For some time it has been recognized that inflammatory mediators released from immune cells can contribute to these persistent pain states. However, it has only recently become clear that immune cell products might have a crucial role not just in inflammatory pain, but also in neuropathic pain caused by damage to peripheral nerves or to the CNS.

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The role of nitric oxide in inflammation and immunity.

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Phase I and pharmacokinetics study of crotoxin (cytotoxic PLA(2), NSC-624244) in patients with advanced cancer.

C. Devin Brisson, Rosa Cabrol, Fernando Silveira … (2002)

A Phase I clinical trial was performed on patients with solid tumors refractory to conventional therapy. Crotoxin was administered i.m. for 30 consecutive days at doses ranging from 0.03 to 0.22 mg/m(2). Patients entered the study after providing a written informed consent. Although 26 patients were entered only 23 were evaluated. Reversible, nonlimiting neuromuscular toxicity evidenced as diplopia because of pareses of the external ocular muscles was present in 13 patients. It started at doses of 0.18 mg/m(2) and lasted from 2 to 6 h. These episodes did not require dose adjustment and disappeared in 1-3 weeks of treatment. Three patients experienced palpebral ptosis, nystagmus (grade 2), and anxiety (grade 2-3) at the dose-limiting toxicity of 0.22 mg/m(2). Also at dose-limiting toxicity, 1 patient showed nystagmus (grade 2) and anxiety (grade 3) without evidence of palpebral ptosis. Transient increases (grades 1-3) in the levels of creatinine kinase, aspartate aminotransferase, and alanine transaminase attributed to crotoxin myotoxicity were observed but returned to normal by the last week of treatment. At 0.21 mg/m(2) there was a case of grade-3 anaphylactic reaction on day 31, which required treatment. Hypersensitivity was regarded as an adverse drug-related reaction, and the patient was removed from the protocol. Two patients at different doses (0.12 mg/m(2) and 0.22 mg/m(2)) had sialorrhea. Four patients had asymptomatic transient increase in blood pressure (up to 20 mm Hg) 12 h after the first injection, which lasted 24 h. No treatment was required and toxicity did not reappear. Six patients experienced slight eosinophilia during the first 2 weeks. The maximum tolerated dose was set at 0.21 mg/m(2). Objective measurable partial responses (>50% reduction of tumor mass) were noted in 2 patients treated at 0.21 mg/m(2) and 1 at 0.12 mg/m(2). One patient (at 0.21 mg/m(2)) presented a complete response on day 110. Crotoxin pharmacokinetics showed rapid absorption from the injection site to blood (t(1/2 A) = 5.2 +/- 0.6 min). Plasma concentration reached a peak (C(max) = 0.79 +/- 0.1 ng/ml) at tau(max) = 19 +/- 3 min. The half-life of the distribution (alpha) phase is 22 +/- 2 min. Starting at 1.5 h after injection, the decrease in plasma concentration becomes slower, reaching 14 +/- 3 pg/ml 24 h after injection. The profile is dominated by the elimination (beta) phase with a half-life of 5.2 +/- 0.6 h. Consequently, 24 h after the injection ( approximately 5 half-life) 97% of the product was eliminated. The area under plasma concentration versus time curve was 0.19 +/- 0.05 microg/min/ml. Assuming availability (F) approximately 1, the clearance is C(L) = 26.3 +/- 7 ml/min, and the apparent volume of distribution is V(d) = 12 +/- 3 liter/kg. The recommended dose for a Phase II study is 0.18 mg/m(2).

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Author and article information

Contributors

Yeping Ruan

Li Yao

Bingbing Zhang

Shuijuan Zhang

Jianyou Guo

Journal

Journal ID (nlm-ta): BMC Complement Altern Med

Journal ID (iso-abbrev): BMC Complement Altern Med

Title: BMC Complementary and Alternative Medicine

Publisher: BioMed Central

ISSN (Electronic): 1472-6882

Publication date Collection: 2013

Publication date (Electronic): 15 April 2013

Volume: 13

Page: 86

Affiliations

[1 ]College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, P.R China

[2 ]Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, P.R China

Article

Publisher ID: 1472-6882-13-86

DOI: 10.1186/1472-6882-13-86

PMC ID: 3680338

PubMed ID: 23587180

SO-VID: 4d66a7da-2618-4f64-87c0-80402e3ef11f

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Anti-inflammatory effects of Neurotoxin-Nna, a peptide separated from the venom of Naja naja atra

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Abstract

Background

Methods

Results

Conclusions

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The International Journal of Person Centered Medicine

Most cited references 17

Role of the immune system in chronic pain.

The role of nitric oxide in inflammation and immunity.

Phase I and pharmacokinetics study of crotoxin (cytotoxic PLA(2), NSC-624244) in patients with advanced cancer.

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