Derangement of hemopoiesis and hematological indices in Khat (Catha edulis) - treated rats

The purpose of this study was to identify the sub-acute toxic effects of Khat (Catha edulis) on hemopoiesis and hematological indices of white albino rats. Two groups, each of 10 rats, were used. In the experimental group, a hydro-ethanol extract of C. edulis was administered orally to rats, daily, in single doses of 500 mg/kg body weight, for for weeks. The control group received equivalent amounts of normal saline. Our results show, for the first time, that oral administration of C. edulis hydro-ethanol extract caused significant derangement in hemopoiesis and in gross hematological indices in rats, characterized by macrocytic anemia and leucopenia. Our data show statistically significant decreases in total leukocytes count (TLC) in which, hemoglobin concentration (Hb. conc.), packed cell volume (PCV), and red cell count (RCC), accompanied by significant increases in mean cell volume (MCV), red blood cell distribution width (RDW) and platelets count with no change in mean hemoglobin concentration (MHC). In peripheral blood smears (PBS) of treated rats, there were evidences of dyserythropoiesis- impaired hemoglobinization, macrocytosis, poikilocytosis and anisocytosis, and dysgranulopoiesis- giant forms, hypersegmented neutrophils and bizarre nuclear shapes. In conclusion, our results indicate that oral administration of a hydro-ethanol extract of C. edulis adversely affected blood cell formation and induced macrocytic anemia and leukopenia in rats. However, the exact mechanisms of these hematological changes produced by Khat are still in need for further studies.Keywords:Catha edulis, hemopoiesis, anemia, leukopenia, ratsAfrican Journal of Biotechnology, Vol. 13(2), pp. 349-355, 8 January, 201

Natural Hypoxia is Not a Limiting Factor in Evaluating the Novel Arylidene Derivative MLT-401 Against an In Vitro Colorectal Cancer Model

Background/Aims: Cancer cells in vivo develop resistance to many anti-tumor drugs. One known factor to influence such drug resistance is hypoxia, which is an important component of the tumor microenvironment. Standard cancer lines mostly do not exhibit a cellular hypoxic microenvironment and there is a paucity of information on the efficacy of lead molecules in both cellular- and environment-induced hypoxic conditions. Therefore, in the present study, we have evaluated the efficacy of the arylidene derivative MLT-401, a lead molecule showing activity against colorectal cancer model using the HCT 116 cell line and CCD-80-C control cells in normoxic and natural (marginal) hypoxic conditions, which is usually observed in high-altitude regions. Methods: The efficacy of MLT-401 on HCT 116 and CCD-80-C cells were tested in both normoxia and marginal hypoxia conditions. MTT assay was used to evaluate cell proliferation, Annexin V binding assay for apoptotic cell quantification and PI staining for cell cycle were done by flow cytometry. Induction of pro-apoptotic marker BAX and anti-apoptotic Bcl-2 were assessed by western blot. Bcl-2/BAX ratio was calculated based on protein expression by western blotting and bands were quantified by Image J software. Results: Analysis of cell proliferation showed an average 10-fold reduction in the inhibition of HCT 116 cells in hypoxic conditions with approximately 500 nM MLT-401, while there was no significant change noted in marginal hypoxic conditions. A proportionate increase in the number of apoptotic cells and large M4 fraction of 10.5% and 26.7% of HCT116 against 6.3% of control cells in cell cycle assessment with MLT-401 concentrations ranging from 250 to 500 nM respectively clearly demonstrated anti-cancer activity. A Bcl-2/BAX ratio of < 1 showed that the induction of apoptosis was the gross mechanism underlying the inhibition of HCT 116 cells by MLT-401. Conclusion: Collectively, these results show MLT-401 as an effective anti-colorectal cancer lead molecule irrespective of normoxia or natural hypoxia

Augmentation of peripheral chemosensitivity during hypermetabolism : a role in exercise hyperpnoea?

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