Beneficial effect of crotamine in the treatment of myasthenic rats

Silva, Saraguaci Hernandez-Oliveira e; Rostelato‐Ferreira, Sandro; Silva, Thomaz Augusto Alves da Rocha e; Randazzo-Moura, Priscila; Belo, Cháriston André Dal; Sanchez, Eládio Flores; Oliveira, Caroline; Rodrigues‐Simioni, Léa

doi:10.1002/mus.23714

Cited by 12 publications

(12 citation statements)

References 25 publications

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“…Crotamine is a strong basic polypeptide myotoxin consisting of 42 amino acid residues present in the venom of the Crotalus durissus terrificus , the South American rattlesnake. Studies have investigated its potential therapeutic applicability, although there is a lack of data related to the safety assessment of this toxin [ 4 , 5 ]. Mello and Cavalheiro [ 15 ] studied the induction of neuropathological changes by the infusion of Cdt venom at hippocampus, but they did not investigate the toxicological aspects related to the intrahippocampal infusion of Cdt venom.…”

Section: Discussionmentioning

confidence: 99%

“…Studies with the rattlesnake venoms are carry out mainly to understand the mechanism of action of proteins present in these poisons in order to improve the treatment against the snakebite accidents. However, toxic components of the Cdt venom, as crotamine, has shown properties with potential for therapeutic purposes [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Considering the crotamine pharmacology, recent studies have shown possible therapeutic applicabilities for this toxin. Hernandez-Oliveira e Silva et al [ 4 ] showed the benefits of using crotamine in the treatment of myasthenia gravis, an autoimmune disease characterized by a dysfunction at the neuromuscular junction, resulting in episodes of muscle weakness and abnormal fatigue [ 12 ]. In their study, animals treated with crotamine showed progressive and sustained muscle contractions, as well as an improvement in exercise tolerance [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Hernandez-Oliveira e Silva et al [ 4 ] showed the benefits of using crotamine in the treatment of myasthenia gravis, an autoimmune disease characterized by a dysfunction at the neuromuscular junction, resulting in episodes of muscle weakness and abnormal fatigue [ 12 ]. In their study, animals treated with crotamine showed progressive and sustained muscle contractions, as well as an improvement in exercise tolerance [ 4 ]. The application of crotamine induced a decrease in the episodes of muscle fatigue compared to animals treated with neostigmine, a common clinical agent used in the myasthenia treatment [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…In their study, animals treated with crotamine showed progressive and sustained muscle contractions, as well as an improvement in exercise tolerance [ 4 ]. The application of crotamine induced a decrease in the episodes of muscle fatigue compared to animals treated with neostigmine, a common clinical agent used in the myasthenia treatment [ 4 ]. Recently, crotamine was proven to be a cell-penetrating peptide that can mediate the drug delivery, being cytotoxic to neoplasic cells [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Intrahippocampal Infusion of Crotamine Isolated from Crotalus durissus terrificus Alters Plasma and Brain Biochemical Parameters

Gonçalves

Vargas

Lara

et al. 2014

IJERPH

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Crotamine is one of the main constituents of the venom of the South American rattlesnake Crotalus durissus terrificus. Here we sought to investigate the inflammatory and toxicological effects induced by the intrahippocampal administration of crotamine isolated from Crotalus whole venom. Adult rats received an intrahippocampal infusion of crotamine or vehicle and were euthanized 24 h or 21 days after infusion. Plasma and brain tissue were collected for biochemical analysis. Complete blood count, creatinine, urea, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), creatine-kinase (CK), creatine kinase-muscle B (CK-MB) and oxidative parameters (assessed by DNA damage and micronucleus frequency in leukocytes, lipid peroxidation and protein carbonyls in plasma and brain) were quantified. Unpaired and paired t-tests were used for comparisons between saline and crotamine groups, and within groups (24 h vs. 21 days), respectively. After 24 h crotamine infusion promoted an increase of urea, GOT, GPT, CK, and platelets values (p ≤ 0.01), while red blood cells, hematocrit and leukocytes values decreased (p ≤ 0.01). Additionally, 21 days after infusion crotamine group showed increased creatinine, leukocytes, TBARS (plasma and brain), carbonyl (plasma and brain) and micronucleus compared to the saline-group (p ≤ 0.01). Our findings show that crotamine infusion alter hematological parameters and cardiac markers, as well as oxidative parameters, not only in the brain, but also in the blood, indicating a systemic pro-inflammatory and toxicological activity. A further scientific attempt in terms of preserving the beneficial activity over toxicity is required.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Intrahippocampal Infusion of Crotamine Isolated from Crotalus durissus terrificus Alters Plasma and Brain Biochemical Parameters

Gonçalves

Vargas

Lara

et al. 2014

IJERPH

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New generation of cell‐penetrating peptides: Functionality and potential clinical application

Reißmann

Filatova

2021

Journal of Peptide Science

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Cell‐penetrating peptides (CPPs) can transport various cargoes through membranes of live cells. Since the first generations of CPPs suffered from insufficient cell and tissue selectivity, stability against proteases, and escape from endosomes, a new generation of peptides, with optimized properties, was developed. These are either derived from natural sources or created through the combination of multivalent structures. The second method allows achieving high internalization efficiency, high cell and tissue selectivity, and release from endosomes via hybrid structures, combining sequences for endosomal release, homing sequences, and sequences for activation at the target tissue and for local delivery of cargoes. CPPs with innate tumor selectivity include azurin, crotamine, maurocalcine, lycosin‐I, buffalo cathelicidin, and peptide CB5005. Some of them can penetrate the membranes of live cells and influence intracellular signaling pathways, thereby exerting cytotoxic effects against tumor cells. To obtain multilayer penetration and stabilization against proteolytic degradation, as well as for better handling, CPPs are often conjugated to nanoparticles. A special problem for tumor treatment is the efficiency of drug transport through three‐dimensional cell cultures. Therefore, the capability of CPPs to deliver the drug even to the innermost tissues is of crucial importance. Notably, the ability of certain CPPs to penetrate barriers such as skin, the blood‐brain barrier (BBB), and cornea or conjunctiva of eyes enabled the replacement of dangerous and painful injections with soothing sprays, creams, and drops. However, it is difficult to rank the efficacy of CPPs because transport efficiency and tissue selectivity depend not only on the CPP itself but also on the target tissue or organ, as well as on the cargo and method of CPP‐cargo coupling. Therefore, the present review describes some examples of new‐generation CPPs and aims to provide advice on how to find or create the right CPP for a given task.

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Crotamine: Function Diversity and Potential Applications

et al. 2017

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Beneficial effect of crotamine in the treatment of myasthenic rats

Abstract: These results indicate that crotamine is more efficient than neostigmine for enhancing muscular performance in myasthenic rats, possibly by improving the safety factor of neuromuscular transmission.

Cited by 12 publications

References 25 publications

Intrahippocampal Infusion of Crotamine Isolated from Crotalus durissus terrificus Alters Plasma and Brain Biochemical Parameters

Intrahippocampal Infusion of Crotamine Isolated from Crotalus durissus terrificus Alters Plasma and Brain Biochemical Parameters

New generation of cell‐penetrating peptides: Functionality and potential clinical application

Crotamine: Function Diversity and Potential Applications

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