Crotoxin alters lymphocyte distribution in rats: Involvement of adhesion molecules and lipoxygenase-derived mediators

Zambelli, Vanessa O.; Sampaio, Sandra Coccuzzo; Sudo-Hayashi, Lia Siguemi; Greco, Karin Vicente; Britto, Luiz Roberto; Alves, A.S.; Zychar, Bianca Cestari; Gonçalves, L.R.C.; Spadacci-Morena, Diva Denelle; Otton, Rosemari; Della-Casa, Maisa S.; Curi, Rui; Cury, Yara

doi:10.1016/j.toxicon.2008.03.004

Cited by 38 publications

(33 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…20 Anti-inflammatory, immunomodulatory, and analgesic effects of crotoxin have also been reported. [21][22][23][24] The synthesized γ-chain of the CA subunit of crotoxin, crotalphine, induces potent antinociception in neuropathic pain by acting at peripheral opioid receptors. 25 To date, elucidation of the three-dimensional (3D) structure of the intact crotoxin heterodimeric complex has presented a major challenge.…”

Section: Introductionmentioning

confidence: 99%

Crystal Structure of Crotoxin Reveals Key Residues Involved in the Stability and Toxicity of This Potent Heterodimeric β-Neurotoxin

Faure¹,

Xu²,

Saul³

2011

Journal of Molecular Biology

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Crystal Structure of Crotoxin Reveals Key Residues Involved in the Stability and Toxicity of This Potent Heterodimeric β-Neurotoxin

Faure¹,

Xu²,

Saul³

2011

Journal of Molecular Biology

View full text Add to dashboard Cite

“…Among the major adhesion molecules involved in cell transmigration is L-selectin, a molecule indispensable for adhesion, diapedesis and subsequent cell migration to the tissue [60, 61]. Thus, the importance of cell influx to the hyperalgesic effect induced by MT-II was investigated using fucoidan, a binder of L-selectin which is able to inhibit cell migration into the tissue in a dose that does not affect the number of circulating leukocytes [41]. Our data showing that fucoidan fully reverted the hyperalgesia induced by MT-II confirmed the importance of cell influx to the joint to MT-II-induced hyperalgesia.…”

Section: Discussionmentioning

confidence: 99%

Articular inflammation induced by an enzymatically-inactive Lys49 phospholipase A2: activation of endogenous phospholipases contributes to the pronociceptive effect

Dias

Sampaio

Sant’Anna

et al. 2017

J Venom Anim Toxins Incl Trop Dis

Self Cite

View full text Add to dashboard Cite

BackgroundArthritis is a set of inflammatory conditions that induce aching, stiffness, swelling, pain and may cause functional disability with severe consequences to the patient’s lives. These are multi-mediated pathologies that cannot be effectively protected and/or treated. Therefore, the aim of this study was to establish a new model of acute arthritis, using a Lys49-PLA2 (Bothrops asper myotoxin II; MT-II) to induce articular inflammation.MethodsThe articular inflammation was induced by MT-II (10 μg/joint) injection into the left tibio-tarsal or femoral-tibial-patellar joints. Cellular influx was evaluated counting total and differential cells that migrated to the joint. The plasma extravasation was determined using Evans blue dye. The edematogenic response was evaluated measuring the joint thickness using a caliper. The articular hypernociception was determined by a dorsal flexion of the tibio-tarsal joint using an electronic pressure-meter test. The mediators involved in the articular hypernociception were evaluated using receptor antagonists and enzymatic inhibitors.ResultsPlasma extravasation in the knee joints was observed 5 and 15 min after MT-II (10 μg/joint) injection. MT-II also induced a polymorphonuclear cell influx into the femoral-tibial-patellar joints observed 8 h after its injection, a period that coincided with the peak of the hyperalgesic effect. Hyperalgesia was inhibited by the pretreatment of the animals with cyclooxygenase inhibitor indomethacin, with type-2 cyclooxygenase inhibitor celecoxib, with AACOCF3 and PACOCF3, inhibitors of cytosolic and Ca2+-independent PLA2s, respectively, with bradykinin B2 receptor antagonist HOE 140, with antibodies against TNFα, IL-1β, IL-6 and CINC-1 and with selective ET-A (BQ-123) and ET-B (BQ-788) endothelin receptors antagonists. The MT-II-induced hyperalgesia was not altered by the lipoxygenase inhibitor zileuton, by the bradykinin B1 receptor antagonist Lys-(Des-Arg9,Leu8)-bradykinin, by the histamine and serotonin antagonists promethazine and methysergide, respectively, by the nitric oxide inhibitor LNMMA and by the inhibitor of matrix 1-, 2-, 3-, 8- and 9- metalloproteinases GM6001 (Ilomastat).ConclusionThese results demonstrated the multi-mediated characteristic of the articular inflammation induced by MT-II, which demonstrates its relevance as a model for arthritis mechanisms and treatment evaluation.

show abstract

“…Several lines of evidence indicate that crotoxin (CTX) displays immunomodulatory and anti-inflammatory activities that affect the cellular and vascular component of inflammatory and immune responses. 25,26) by interfering with the activity of leukocytes. 27) This toxin also inhibits cytokine release (e.g., IL-2, IL-4 and IL-10) in human serum albumin-immunized mice.…”

Section: Discussionmentioning

confidence: 99%

“…25,26) by interfering with the activity of leukocytes. 27) This toxin also inhibits cytokine release (e.g., IL-2, IL-4 and IL-10) in human serum albumin-immunized mice.…”

Section: Discussionmentioning

confidence: 99%

Behavioral and Morphological Evidence for the Involvement of Glial Cells in the Antinociceptive Effect of Najanalgesin in a Rat Neuropathic Pain Model

Liang

Jiang

Zhang

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Neuropathic pain is a devastating neurological disease that seriously affects patients' quality of life. Despite a high level of incidence, the underlying mechanisms of neuropathic pain are still poorly understood. However, recent evidence supports the prominent role of spinal glial cells in neuropathic pain states. In our laboratory, we observed that najanalgesin, a novel peptide isolated from the venom of Naja naja atra, exerts significant analgesic effects on acute pain in mice and neuropathic pain in rats. The objective of the present study was to determine whether spinal glia are associated with the antinociceptive effect of najanalgesin in an L5 spinal nerve ligation (SNL) rodent model of neuropathic pain. Mechanical allodynia developed after surgery, and hypersensitivity was significantly attenuated by the intrathecal administration of najanalgesin. The inhibitory effect of najanalgesin was significantly (p<0.05) enhanced after pretreatment with fluorocitrate (a glial cell antagonist). In addition, the astrocyte activation was attenuated following najanalgesin treatment in the dorsal horn of neuropathic rats, as assessed by immunohistology and Western blotting. The tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) content of cerebral spinal fluid and cell culture supernatants changed significantly after najanalgesin administration. The results suggest that najanalgesin may exert its anti-allodynic effect by altering astrocyte cell function.

show abstract

Crotoxin alters lymphocyte distribution in rats: Involvement of adhesion molecules and lipoxygenase-derived mediators

Cited by 38 publications

References 57 publications

Crystal Structure of Crotoxin Reveals Key Residues Involved in the Stability and Toxicity of This Potent Heterodimeric β-Neurotoxin

Crystal Structure of Crotoxin Reveals Key Residues Involved in the Stability and Toxicity of This Potent Heterodimeric β-Neurotoxin

Articular inflammation induced by an enzymatically-inactive Lys49 phospholipase A2: activation of endogenous phospholipases contributes to the pronociceptive effect

Behavioral and Morphological Evidence for the Involvement of Glial Cells in the Antinociceptive Effect of Najanalgesin in a Rat Neuropathic Pain Model

Contact Info

Product

Resources

About