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The objective of this study was to identify the possible involvement of the GABAergic system in the anesthetic effect of Lippia alba essential oil (EO). We propose a new animal model using silver catfish (Rhamdia quelen) exposed to an anesthetic bath to study the mechanism of action of EO. To observe the induction and potentiation of the anesthetic effect of EO, juvenile silver catfish (9.30 ± 1.85 g; 10.15 ± 0.95 cm; N = 6) were exposed to various concentrations of L. alba EO in the presence or absence of diazepam [an agonist of high-affinity binding sites for benzodiazepinic (BDZ) sites coupled to the GABAA receptor complex]. In another experiment, fish (N = 6) were initially anesthetized with the EO and then transferred to an anesthetic-free aquarium containing flumazenil (a selective antagonist of binding sites for BDZ coupled to the GABAA receptor complex) or water to assess recovery time from the anesthesia. In this case, flumazenil was used to observe the involvement of the GABA-BDZ receptor in the EO mechanism of action. The results showed that diazepam potentiates the anesthetic effect of EO at all concentrations tested. Fish exposed to diazepam and EO showed faster recovery from anesthesia when flumazenil was added to the recovery bath (12.0 ± 0.3 and 7.2 ± 0.7, respectively) than those exposed to water (9.2 ± 0.2 and 3.5 ± 0.3, respectively). In conclusion, the results demonstrated the involvement of the GABAergic system in the anesthetic effect of L. alba EO on silver catfish.

The effect of the antioxidant gallic acid (GA) on Pb toxicity in blood, liver and kidney was investigated in the present study. Rats Wistar received Pb nitrate (50 mg/Kg/day, i.p., 5 days) followed by GA (13.5 mg/Kg, p.o., 3 days) or a chelating agent (EDTA, 55 mg/Kg, i.p.). As result, Pb decreased body weight, hematocrit and blood δ-aminolevulinic acid dehydratase (ALA-D) activity. In addition, high Pb levels were observed in blood and tissues, together with increased (1) lipid peroxidation in erythrocytes, plasma and tissues, (2) protein oxidation in tissues and (3) plasma aspartate transaminase (AST) levels. These changes were accompanied by decreasing in antioxidant defenses, like superoxide dismutase (SOD) activity in tissues and catalase (CAT) activity and reduced glutathione (GSH) in liver. GA was able to reverse Pb-induced decrease in body weight and ALA-D activity, as well as Pb-induced oxidative damages and most antioxidant alterations, however it did not decrease Pb bioaccumulation herein as EDTA did. Furthermore, EDTA did not show antioxidant protection in Pb-treated animals as GA did. In conclusion, GA decreased Pb-induced oxidative damages not by decreasing Pb bioaccumulation, but by improving antioxidant defenses, thus GA may be promising in the treatment of Pb intoxications.

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Intracellular peptides generated by limited proteolysis are likely to function inside and outside cells and could represent new possibilities for drug development. Here, we used several conformational-sensitive antibodies targeting G-protein coupled receptors to screen for novel pharmacological active peptides. We find that one of these peptides, DITADDEPLT activates cannabinoid type 1 receptors. Single amino acid modifications identified a novel peptide, DIIADDEPLT (Pep19), with slightly better inverse agonist activity at cannabinoid type 1 receptors. Pep19 induced uncoupling protein 1 expression in both white adipose tissue and 3T3-L1 differentiated adipocytes; in the latter, Pep19 activates pERK1/2 and AKT signaling pathways. Uncoupling protein 1 expression induced by Pep19 in 3T3-L1 differentiated adipocytes is blocked by AM251, a cannabinoid type 1 receptors antagonist. Oral administration of Pep19 into diet-induced obese Wistar rats significantly reduces adiposity index, whole body weight, glucose, triacylglycerol, cholesterol and blood pressure, without altering heart rate; changes in the number and size of adipocytes were also observed. Pep19 has no central nervous system effects as suggested by the lack of brain c-Fos expression, cell toxicity, induction of the cannabinoid tetrad, depressive- and anxiety-like behaviors. Therefore, Pep19 has several advantages over previously identified peripherally active cannabinoid compounds, and could have clinical applications.