Avaliação do efeito tóxico e influência comportamental do alcaloide imidazólico epiisopiloturina de Pilocarpus microphyllus no modelo experimental de neuropatia do nervo safeno em Rattus novergicus

Abstract

Neuropathic pain is classified as chronic pain characterized by damage to sensory nerve fibers, causing allodynia and hyperalgesia. Current pharmacotherapy is restricted to the off-label use of drugs used in other diseases, so medicinal plants can provide new options for the treatment of neuropathic pain. In this context, Epiisopiloturine (EPIT) has been highlighted, an alkaloid isolated from a by-product during the extraction of pilocarpine from the leaves of Pilocarpus microphyllus. Therefore, the aim of the present study was to evaluate the effect of EPIT on blood biochemical parameters and animal behavior during its evaluation in the model of neuropathic pain in rats. The animals were treated with EPIT (1.5; 3, 4 and 5 mg/kg, p.o.) and biochemical parameters (creatinine, urea, HDL, triglycerides), hematological and behavioral parameters were evaluated, parallel to the evaluation of antinociceptive activity (Von test Frey), to preliminarily evaluate possible EPIT toxicity. The behavioral evaluation was carried out through the open field test. After the behavioral tests, the animals were euthanized for the collection of liver tissue (determination of reduced glutathione (GSH) and malondialdehyde (MDA) and kidneys for histopathological analysis together with the liver. EPIT (1.5; 3 and 4.5 mg/kg) was able to increase the pain threshold in animals that had the substance administered, in addition to positively influencing behavior by increasing the number of crossings and grooming in the open field test. EPIT did not significantly interfere with the increase in levels of GSH and MDA induced by neuropathy. Biochemical parameters (urea, creatinine, HDL and triglycerides) did not differ significantly in relation to the control group (untreated). No changes were observed in the number of red blood cells, platelets and hemoglobin. Histopathological analysis of the hepatic and renal tissue showed some alterations (assessed by scores) induced by EPIT (1.5; 3 and 4.5 mg/kg).In the kidneys, the dose of 1.5 mg/kg increased vascular congestion r and cellular infiltrate, while in the liver the highest doses were those that induced alterations in relation to the control group (neuropathy, untreated). In conclusion, our study showed, for the first time, the antinociceptive effect of EPIT in the model of neuropathic pain induced by saphenous nerve ligation, which does not seem to be associated with biochemical, hematological toxicity, and regarding histopathological studies, additional studies are on the agenda of research, although the data suggest an absence of important toxicity.