The intrahippocampal infusion of crotamine from Crotalus durissus terrificus venom enhances memory persistence in rats

Vargas, Liane S.; Lara, Marcus Vinicius Soares de; Gonçalves, Rithiele; Mandredini, Vanusa; Ponce-Soto, Luis Alberto; Marangoni, Sérgio; Belo, Cháriston André Dal; Mello‐Carpes, Pâmela Billig

doi:10.1016/j.toxicon.2014.04.017

Cited by 11 publications

(12 citation statements)

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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%

“…In this work, we have demonstrated that a single intrahippocampal infusion of crotamine induced acute and chronic alterations in hematological and cardiac parameters in blood and promoted sub-acute oxidative stress in plasma and brain. It is worth mentioning that we recently demonstrated, that a single intrahippocampal infusion of crotamine can promote memory persistence [ 5 ], highlighting that crotamine could be a potential pharmacological tool, especially in case of diseases that involve memory persistence deficits, as Alzheimer disease. We now showed that crotamine infusion induced alterations in creatinine, CK, leukocytes, platelets, urea, GOT, GPT, red blood cells and hematocrit in the blood; and TBARS, carbonyl and micronucleus in the plasma and brain tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Crotamine isolated from Cdt venom was a reminiscent stock and was supplied by Dr. Sérgio Marangoni from Laboratory of Protein Chemistry (LAQUIP) (UNICAMP, Campinas-SP, Brazil) and was prepared daily by dilution in saline immediately before use. The crotamine dose was chosen based on previous in vitro [ 9 ] and in vivo [ 5 ] experiments. Reagents for oxidative parameters analysis were purchased from Sigma (St. Louis, MO, USA), and other reagents used in this study were of analytical grade and obtained from standard commercial supplier.…”

Section: Methodsmentioning

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%

“…We recently showed that intrahippocampal infusion of a single dose of crotamine (1 µg/µL; 1 µL/side) improves after-learning persistence of object recognition and aversive memory [ 5 ]. This result reinforces the potential therapeutic application of crotamine as a novel therapeutic agent to treat diseases related to the CNS function, especially in situations in which the loss of cognitive function is involved, such as dementias.…”

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: Discussionmentioning

confidence: 99%