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

Abstract

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.

Intradermal Application of Crotamine Induces Inflammatory and Immunological Changes In Vivo

“…Moreover, due to its cell-penetrating capacity and site-specific interactions, crotamine has been studied as a drug-mediating peptide and as a model for the discovery of new antitumor molecules [10,17,19,21,22,23]. However, data on crotamine safety for local and systemic application in biological models are scarce [24,25].…”

“…Using an intra-hippocampal application route, Gonçalves et al [25] observed that crotamine altered the oxidative parameters in the serum of animals after 21 days. These results suggest that crotamine has the ability to induce an imbalance in the systemic redox system for a long time, regardless of the route of administration.…”

“…Due to its pharmacological potential, crotamine is considered a promising molecule for clinical use in different biomedical fields [2,3,23]. However, data on its local and systemic safety in biological models are scarce [16,24,25]. Thus, to better understand the in vivo proinflammatory activity of crotamine, we assessed the effects of this toxin on different immunological parameters.…”