Combination Therapy Antimalarial Drugs Mefloquine And Artequin Induce Reactive Astrocytes Formation In The Hippocampus Of Rats

摘要

The normal adult vertebrate nervous system is a relative quiescent tissue in terms of cell proliferation. However, astrocytes in many region of the central nervous system (CNS) like hippocampus retain the capacity to undergo cell division. Understanding the growth of this glial cell is a key to repairing neurons in response to insult. We studied reaction of astrocytes in the hippocampus after a three day administration of antimalarial agent mefloquine and Artequin to forty-two Wistar rats. The rats received 1.07mg/kg, 2.14mg/kg, 4.28mg/kg of mefloquine and 0.86/1.07mg/kg, 171/2.14mg/kg and 3.24/4.28mg/kg of Artequin. Hippocampal sections of treated rats stained by Hortega’s lithium carbonate method revealed astrocytes stained black as in the control, but hippocampal sections of rats treated with 2.14mg/kg, 4.28mg/kg of mefloquine, and 1.71/2.14mg/kg and 3.24/4.28mg/kg of Artequin showed large, numerous and some few paired astrocytes. We conclude that mefloquine and Artequin induced dose dependant reactive astrocytes formation in the hippocampus. This may impair uptake of neurotransmitters and alter neuronal environment, thus altering hippocampal functions like memory and learning.Key words: Artequin, Hippocampus, Mefloquine, Reactive Astrocytes. The research was carried out in the Histology laboratory of the Department of Human Anatomy, Faculty of Basic Medical Sciences, University of Calabar, Calabar, Nigeria Introduction In most parts of Nigeria including Calabar, malaria has become a familiar sickness. Health centres are not often patronized rather home/self treatment is the first-line of treatment as antimalarial drugs are purchased at the open markets like other commodities. In addition, sales persons have little or no formal education on the various antimalarial therapies in use, knowledge of side effects of the drug or contradictions and appropriate dosages. The risk of toxicity this way is high mainly from over dose and misuse; this indiscriminate misuse of drug could endanger the life of the vast population 1 .Antimalarial agents are drugs used in the treatment of malaria infections caused by the Plasmodium species; falciparum, vivax, ovale and malariae. Some of this antimalarial monotherapies include; chloroquine, amodiaquine, mefloquine and artesunate. Mefloquine is a 4-quinoline methanol derivative that has been the drug of choice in most regions of the world. Like chloroquine, it is a blood schizonticide, though has long acting half life than any known antimalarial 1 . Over the years, there has been global decline in the use of mefloquine regime due to its documented neurological adverse effects such as neuropsychiatric disorders, forgetfulness and seizure 2 . In 1980 mefloquine was withdrawn from the pharmaceutical market 1 .The recent trend of malaria therapy with the artemisinin based combination therapy (ACT) such as artemether or artesunate combined with a more slowly eliminated drug has again re-introduced mefloquine combined with artesunate known as Artequin 3 for the treatment of resistant malaria. Though, artemisinin derivatives have little or no neurological adverse effects in humans 4 , there have been poor documentation on their morphological activity and that of Artequin as well 1,5 . However, it has been shown that antimalarial have caused damage to certain organs of the body thus influencing their activity 1 . Neurons in the central nervous system (CNS) are particularly susceptible owing to the wide range of neurological events documented on antimalarial drugs which varies depending on the part of the CNS affected, with dizziness being the most frequently reported 1 .Astrocytes make up half of the cell population in the CNS apart from neurons, they are known to provide neurons with rich nutritional environment for survival. Understanding this glial activity is a clue to neuronal responses. Mefloquine presence in Artequin may indicate a possibility of danger because of the adverse events documented a