Objective: To determine the effect and safety of IV lipid emulsion in rabbits with acute ivermectin toxicosis.Design: Randomized controlled trial.Setting: University research facility.Animals: Twenty-four healthy male adult New Zealand rabbits.Interventions: Three groups of rabbits (IV, IV_RL, and IV_LE) received 80 mg/kg of ivermectin (8 mL/kg) through a nasogastric tube, and 1 group (LE) received an equivalent volume (8 mL/kg) of 0.9% sodium chloride. Group IV_RL was treated with Ringer's lactate (2 mL/kg bolus, followed by 0.25 mL/kg/min for 60 minutes), whereas groups IV_LE and LE received 20% lipid emulsion. The rabbits were submitted to clinical and neurological evaluation, and blood samples were collected for biochemical analysis.All animals were euthanized, and tissue samples were collected and processed for histopathological evaluation and ivermectin quantification.Measurements and main results: All animals exposed to ivermectin manifested clinical changes consistent with toxicosis, but the ones that received IV lipid emulsion infusion showed no significant clinical improvement. Intense increase in serum glucose and triglyceride concentrations was seen after ivermectin exposure, along with increased urea and creatinine concentrations, but the last 2 remained within the reference range.Lipid emulsion caused an intense increase in triglycerides and cholesterol concentrations. No pathological abnormalities were seen in the organs sampled. Toxicological analysis showed greater ivermectin concentration in adipose tissue and liver, followed by kidney and, finally, brain. The treatments did not change ivermectin tissue concentration.
There is evidence of human interactions with plants of the genus Cannabis spp., for several different purposes, for at least 12,000 years. Even so, until the 1960s, studies involving Cannabis were focused on the context of an illicit drug (Backes, 2014). The isolation and characterization of cannabidiol (CBD) (Mechoulam & Shvo, 1963) and Δ9− tetrahydrocannabinol (THC) (Gaoni & Mechoulam, 1964;Mechoulam & Gaoni, 1967), seem to have, once again, awakened the interest of the scientific community to study Cannabis, after a period of neglect. In the 1970s, CBD's antiepileptic effect was demonstrated in mice and rats (Carlini et al., 1973) and later in people with epilepsy (Cunha et al., 1980). From the 1980s onwards, THC receptors in the brain of rats (later called cannabinoid receptors 1 or CB1) were demonstrated (Devane et al., 1988), and an endogenous substance (anandamide) extracted from pig brains which could bind to these same receptors was discovered (Devane et al., 1992), as well as a second cannabinoid receptor (CB2) isolated from human spleen cells (Munro et al., 1993).Thus, the concept of an endocannabinoid system was created, which is present in a wide range of living beings and consists of cannabinoid receptors (CRs) subtypes, binding substances, and enzymes involved in their synthesis and degradation (Landa et al., 2016;
Nerium oleander is an ornamental cardiotoxic plant found in tropical and subtropical areas of the World. Its toxicity is related to the content of cardioactive glycosides, mainly oleandrin, found throughout the plant. The present study aimed to describe a new and improved method for oleandrin detection in tissue samples. The determination of oleandrin was made after extraction with a modified QuEChERS technique and measurement by UFLC-MS/MS. A total of 36 guinea pigs (Cavia porcellus) were distributed into 3 groups (n=12): control group that received only water orally (CON), and two treated groups that received hydroalcoholic oleander extract at doses of 150mg.kg-1 (OLE 150) and 300mg.kg-1 (OLE 300) in single oral dose. After three hours, fragments of heart, kidneys, liver and brain were collected for determination of oleandrin levels. The extraction and chromatographic procedures were effective for oleandrin detection and quantification in tissues, with retention time of 1.2 min and detection limit of 0.001μg g-1. The chromatographic analysis of treated guinea pigs indicated that oleandrin is distributed equally among the analyzed tissues. The developed methodology is a reliable, effective and rapid form of diagnosis of N. oleander poisoning based on necropsy tissue samples.
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