Increase of the cytotoxic effect of Bothrops jararacussu venom on mouse extensor digitorum longus and soleus by potassium channel blockers and by Na+/K+-ATPase inhibition

Tomaz, Marcelo A.; Fernandes, Fabrício Freitas; El-Kik, Camila Z.; Moraes, Raphael A.M.; Calil-Elias, Sabrina; Saturnino-Oliveira, Jeison; Martínez, Ana Maria Blanco; Ownby, Charlotte L.; Melo, Paulo A.

doi:10.1016/j.toxicon.2008.07.003

Cited by 6 publications

(1 citation statement)

References 41 publications

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“…As we previously described, the increase of plasma CK in mice reach a peak at 2 h after intramuscular injection and reflects the sarcolemma damage of skeletal muscle fibers, that we ascribe as myotoxicity [28]. We also showed that isolated mouse EDL or soleus muscle exposed to honeybee venom presents a quick and intense injury, revealed by the rate of CK release [38].…”

Section: Discussionsupporting

confidence: 76%

A Novel Apilic Antivenom to Treat Massive, Africanized Honeybee Attacks: A Preclinical Study from the Lethality to Some Biochemical and Pharmacological Activities Neutralization

Teixeira-Cruz

Strauch

Monteiro-Machado

et al. 2021

Toxins

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Massive, Africanized honeybee attacks have increased in Brazil over the years. Humans and animals present local and systemic effects after envenomation, and there is no specific treatment for this potentially lethal event. This study evaluated the ability of a new Apilic antivenom, which is composed of F(ab’)2 fraction of specific immunoglobulins in heterologous and hyperimmune equine serum, to neutralize A. mellifera venom and melittin, in vitro and in vivo, in mice. Animal experiments were performed in according with local ethics committee license (UFRJ protocol no. DFBCICB072-04/16). Venom dose-dependent lethality was diminished with 0.25–0.5 μL of intravenous Apilic antivenom/μg honeybee venom. In vivo injection of 0.1–1 μg/g bee venom induced myotoxicity, hemoconcentration, paw edema, and increase of vascular permeability which were antagonized by Apilic antivenom. Cytotoxicity, assessed in renal LLC-PK1 cells and challenged with 10 μg/mL honeybee venom or melittin, was neutralized by preincubation with Apilic antivenom, as well the hemolytic activity. Apilic antivenom inhibited phospholipase and hyaluronidase enzymatic activities. In flow cytometry experiments, Apilic antivenom neutralized reduction of cell viability due to necrosis by honeybee venom or melittin. These results showed that this antivenom is effective inhibitor of honeybee venom actions. Thus, this next generation of Apilic antivenom emerges as a new promising immunobiological product for the treatment of massive, Africanized honeybee attacks.

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Section: Discussionsupporting

confidence: 76%

A Novel Apilic Antivenom to Treat Massive, Africanized Honeybee Attacks: A Preclinical Study from the Lethality to Some Biochemical and Pharmacological Activities Neutralization

Teixeira-Cruz

Strauch

Monteiro-Machado

et al. 2021

Toxins

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Histological and functional renal alterations caused by Bothrops alternatus snake venom: Expression and activity of Na+/K+-ATPase

Linardi

Silva

Miyabara

et al. 2011

Biochimica et Biophysica Acta (BBA) - General Subjects

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Effect of heparin treatment on the expression and activity of different ion-motive P-type ATPase isoforms from mouse extensor digitorum longus muscle during degeneration and regeneration after Bothrops jararacussu venom injection

Schaffazick

Amaral

Fonseca

et al. 2010

Toxicon

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Ca(2+) ions are essential to myonecrosis, a serious complication of snake envenomation, and heparin seems to counteract this effect. We investigated the effect of local injection of Bothrops jararacussu venom in mouse fast-twitch extensor digitorum longus (EDL) muscle, without or with heparin, on functional/molecular alterations of two central proteins involved in intracellular Ca(2+) homeostasis, sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and Na(+)/K(+)-ATPase. EDL-specific SERCA1 isoform expression dropped significantly just after venom administration (up to 60% compared to control EDL values at days 1 and 3; p<0.05) while SERCA2 and Na(+)/K(+)-ATPase alpha(1) isoform expression increased at the same time (3-6- and 2-3-fold, respectively; p<0.05). Although not significant, Na(+)/K(+)-ATPase alpha(2) isoform followed the same trend. Except for SERCA2, all proteins reached basal levels at the 7th day. Intravenous heparin treatment did not affect these profiles. Ca(2+)-ATPase activity was also decreased during the first days after venom injection, but here heparin was effective to reinstate activity to control levels within 3 days. We also showed that B. jararacussu venom directly inhibited Ca(2+)-ATPase activity in a concentration-dependent manner. Our results indicate that EDL SERCA and Na(+)/K(+)-ATPase are importantly affected by B. jararacussu venom and heparin has protective effect on activity but not on protein expression.

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Increase of the cytotoxic effect of Bothrops jararacussu venom on mouse extensor digitorum longus and soleus by potassium channel blockers and by Na+/K+-ATPase inhibition

Cited by 6 publications

References 41 publications

A Novel Apilic Antivenom to Treat Massive, Africanized Honeybee Attacks: A Preclinical Study from the Lethality to Some Biochemical and Pharmacological Activities Neutralization

A Novel Apilic Antivenom to Treat Massive, Africanized Honeybee Attacks: A Preclinical Study from the Lethality to Some Biochemical and Pharmacological Activities Neutralization

Histological and functional renal alterations caused by Bothrops alternatus snake venom: Expression and activity of Na+/K+-ATPase

Effect of heparin treatment on the expression and activity of different ion-motive P-type ATPase isoforms from mouse extensor digitorum longus muscle during degeneration and regeneration after Bothrops jararacussu venom injection

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