Abstract
Objective. The purpose of thisstudy was to determine the chronic toxicity of the drug “Harmine hydrochloride, capsules” for preclinical evaluation of its safety.
 Materials and methods.The experiment was performed on 48 CD-1 rats. Harmine hydrochloride was injectedto the animals intragastrically at doses of 2.5 mg / kg/per day, 5 mg / kg/per day, 9 mg / kg/per day, 10 mg / kg/per day for 3 months. After 3 months, the animals were withdrew from the experiment, internal organs (brain, heart, spleen, adrenals) were weighed and set in 10% neutral formalin. Histological specimenswere mounted in accordance with standard procedures.
 Results and Discussion. All morphological, histopathological changes, in addition to mortality and bodyweight changes were recorded.Microtome cuts, 5 micrometers thick, were stained with hematoxylin and eosin.
 Conclusion. As a result of the morphological study, there was no toxic effect of harmine hydrochloride at doses of 2.5 mg / kg, 5 mg / kg, 9 mg / kg and 10 mg / kg on the brain, at doses of 2.5 mg / kg and 5 mg / kg on the structure of the heart, spleen and adrenal glands. At doses of 9 mg / kg and 10 mg / kg, there is an initial toxic dose-dependent effect on the heart, spleen and adrenal glands.
 Bangladesh Journal of Medical Science Vol.18(3) 2019 p.598-606
Highlights
The search and development of herbal medicines is issue of the day[1,2,3].Recently, scientists are attracted by natural heterocyclic compounds, which are the richest source of production of broad-spectrum drugs[4,5].One of the most promising in the series of these compounds is the indole alkaloid harmine, which is comprehensively studied at present time[6,7,8,9,10]
According to the literature data, the neuroprotective effect[11] and the antitumor effect of harmine are discussed[12].According to the opinion ofseveral authors[13], harmine has great prospects, as far as an oncological drug and a combination ofharminee with an inhibitor of non-homologous end joining (NHEJ) can be an effective strategy of anticancer treatment.It has been shown that harmine can inhibit the proliferation of tumor cells and induce the arrest of the G2 / M cell cycle, accompanied by an increase in apoptotic cell death in SGC-7901 cancer cells
Experimental research of Harmine hydrochloride effect on internal organs antigenotoxic and hallucinogenic properties[16,17,18]. It effects on gamma-aminobutyric acid (GABA) type A and monoamine oxidase A or B receptors, enhances insulin sensitivity and causes vasorelaxing effect[19].Harmine prevents the loss of bone tissue, suppressing osteoclastogenesis[20]
Summary
Experimental research of Harmine hydrochloride effect on internal organs antigenotoxic and hallucinogenic properties[16,17,18] It effects on gamma-aminobutyric acid (GABA) type A and monoamine oxidase A or B receptors, enhances insulin sensitivity and causes vasorelaxing effect[19].Harmine prevents the loss of bone tissue, suppressing osteoclastogenesis[20]. Harmine activates both internal and external pathways of apoptosis, and regulates some transcription factors and proinflammatory cytokines[21,22,23].Harminewas registered as an inhibitor of the hypotensive specific kinase (DYRK1A), which regulates cell proliferation and brain development[24].Harmine has a potential bioinsecticidal effect on the larvae of the insect pest, Plodiainterunctella[25]. When choosing the doses for the study of chronic toxicity of the drug “Harminee hydrochloride, capsules”
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