In vivo acute toxicity assessment of a novel quinoxalinone (6-nitro-2 (1H)-quinoxalinone) in Wistar rats

The quinoxaline derivatives are an important class of heterocyclic compounds, obtained from chemical azote replacement of carbone atom. Fusion of quinoxaline production is relatively easy as they are obviously synthesized by the fusion of two aromatic rings, benzene and pyrazine. The new quinoxalinique derivative, 6-nitro-2 (1H)-quinoxalinone (NQX), has been synthesized in our laboratory. However, the related toxic effect on rat remains unknown. The present work aims to study the acute toxicity of NQX in normal Wistar rats. Seven groups of female rats received an intraperitoneal (i.p.) injection of 0 (control), 20, 40, 60, 120, 200 and 300 mg/kg of the NQX and followed for 14 days. Mortalities, behavioural changes, weight, changes in food and water uptake, urine output and weight of faeces were monitored. At the end of the experiment, the rats receiving the no-observed-adverse-effect level (NOAEL) are sacrificed, blood and organs were collected and haematological and biochemical parameters were analysed in sera sample. The results showed that the NQX Lethal Dose 50 (LD50) was 161.16 mg/kg. The administration of NQX at a dose of 40 mg/kg (NOAEL dose) did not affect animal viability and body weight. In addition, food intake, water intake and urine output remain unchanged. Furthermore, at the NOAEL dose, the levels of blood cells (erythrocytes and leukocytes), haemoglobin, biochemical parameters (glucose, cholesterol, triglycerides, urea, creatinine, bilirubin, total protein and transaminase) and organ’s weights *Corresponding author: R. Nakache, Faculté des Sciences, Laboratoire de Génétique, Neuroendocrinologie et Biotechnologie, Kenitra, Maroc E-mail: [email protected] Reviewing editor: Youcef Mehellou, Cardiff University, UK Additional information is available at the end of the article ABOUT THE AUTHORS R. Nakache PhD is presently preparing his PhD at the Neuroendocrinology Unit, Genetics, Neuroendocrinology and Biotechnology Laboratory, Department of Biology, Faculty of science, Ibn Tofail University, Morocco. His research focuses on drug discovery and investigation into novel compounds for eventual anti-anxiety-like and/or anti-depressive-like effects belonging to the family of quinoxalines derivatives under the supervision of professor Abdelhalem Mesfoui. A. Mesfioui, PhD, is presently working as a professor of neurosciences/pharmacology at biology department, Ibn Tofail University, Morocco. He is the head at the Genetics, Neuroendocrinology and Biotechnology Laboratory, obtained his first PhD from the University of Nancy, France in 1988 and his second PhD from Ibn Tofail University in 1997. He is a member of the New York Academy of Sciences. PUBLIC INTEREST STATEMENT The profiles of undesirable effects of current drugs have made the search for new treatments, free of such side effects and a critical track. In order to find more safe substitutes to the therapeutic molecules currently used, and in order to respond to the phenomenon of efficacy decline due to the emergence of resistance, researchers study several families of compounds, amongst them, the family of quinoxaline derivatives, that can have a broad spectrum of potential biological applications. In fact, after the synthesis of any biologically active molecule and prior to clinical trials, toxicological study to assess the range of its non-toxic doses is necessary for the safety of its use. Therefore, the objective of this work was to determine the acute toxicity of our newly synthesized molecule, the NQX that shows, in our study, very promising properties effect compared to similar compound on the market. Received: 12 January 2017 Accepted: 27 February 2017 First Published: 03 March 2017 Page 2 of 11 © 2017 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license. R. Nakache