Aboudoulatif Diallo

Effect of Tectona grandis on phenylhydrazine-induced anaemia in rats.

Traditional oral report indicates that Tectona grandis is used in the treatment of anaemia in Togo. For this purpose, the extract of T. grandis leaves is evaluated on anaemia model of rat induced by intraperitoneal injection of phenylhydrazine at 40 mg/kg for 2 days. Oral administration of T. grandis extract at 1 g/kg/day and 2 g/kg/day, to the rats previously treated with phenylhydrazine, increased the concentration of haemoglobin, red blood cells number, haematocrit and reticulocytes rate. Moreover, the extract of T. grandis enhanced the osmotic resistance of the red blood cells that confirm the important presence of young red blood cells. These results support partially the traditional use of T. grandis in the treatment of anaemia.

Study of Epigenetic Properties of Poly(HexaMethylene Biguanide) Hydrochloride (PHMB)

Poly(HexaMethylene Biguanide) hydrochloride (PHMB) CAS No. [32289-58-0] is a particularly effective member of the biguanides antiseptic chemical group, and has been in use since the early fifties in numerous applications. It has been proposed that PHMB be classified as a category 3 carcinogen although PHMB is not genotoxic. It has been hypothesized that PHMB may have epigenetic properties effects, including non-genotoxic modifications of DNA bases, DNA methylation and mitogenic cytokine production. These properties have been assessed in vitro using 3 cell types: Caco-2 cells (from a human colon adenocarcinoma) with a non-functional p53 gene. (∆p53: mut p53), N2-A (Neuro-2A cells, mouse neural cells), the brain being a possible target organ in rodents and HepG2 cells (human hepatocellular carcinoma) with functional p53 gene. From the concentration 1 μg/mL up to 20 μg/mL of PHMB, no effect was observed, either growth stimulation or inhibition. Viability testing using neutral red led to an IC 50 of 20–25 μg/mL after treatment with PHMB for 3 h, whereas the MTT test led to IC50 values of 80 μg/mL, 160 μg/mL and 160 μg/mL respectively for HepG2 cells, Neuro-2A cells and Caco-2 cells. PHMB does not induce significant oxidative stress (production of MDA or lipoperoxidation, nor does it induce hydroxylation of DNA (8-OH-dG) and/or its hypermethylation (m5dC), the latter being strongly implicated in DNA replication and regulation and cell division. PHMB does not induce significant production of mitogenic cytokines such as TNF-α (tumor necrosis factor), interleukins (IL-1 alpha), and the transcription factor nuclear factor kappa B (NF-κB) which can cause either apoptosis or stimulate the growth of transformed cells or tumors. Instead, from concentrations of 20 to 100 μg/mL, PHMB kills cells of all types in less than 3 h. The expression of genes involved in the mechanisms of cell death induced by PHMB, including p53, the pro apoptotic gene bax and others, the anti-apoptotic bcl-2 and caspase-3 has been evaluated by RT-PCR. Finally, the status of GAP-junctions (GJIC) in the presence of PHMB has been determined and appeared to not be significantly affected. Taken together the data show that in vitro PHMB does not exhibit clear and remarkable epigenetic properties except a slight increase of some cytokines and transcription factor at higher concentrations at which cell lysis occurs rapidly.

In vivo and in vitro toxicological evaluation of the hydroalcoholic leaf extract of Ageratum conyzoides L. (Asteraceae)

ETHNOPHARMACOLOGICAL RELEVANCE In African traditional medicine, Ageratum conyzoides has been used as purgative, febrifuge, anti-ulcer and wound dressing. To date there is no safety information about long term use of Ageratum conyzoides which contains pyrrolizidine alkaloids, a class of hepatotoxic and carcinogenic phytochemicals. This study aims to evaluate the 90 days subchronic toxicity and in vitro toxicity of Ageratum conyzoides. MATERIALS AND METHODS Three groups of 8 rats (4 males and 4 females) received distilled water (control), 500 and 1000 mg/kg of the extract daily for 90 consecutive days by oral gavage. The animals were observed daily for abnormal clinical signs and death. Body weight, relative organ weight, haematological and biochemical parameters of blood as well as heart, kidney, liver and spleen tissues histology were evaluated. RESULTS After 90 days administration, Ageratum conyzoides increased significantly (p<0.05) the relative weight of the liver, the spleen and kidney as compared to control group. Ageratum conyzoides increased also significantly (p<0.05) ALP, ALT, AST and blood glucose. Furthermore, an increase in the number of platelets associated with a normocytic and normochromic anaemia was observed. The cytotoxicity, determined by the MTT test and neutral red assay, has shown that the cytotoxicity of hydroalcoholic extract of Ageratum conyzoides and its total alkaloids was very close. CONCLUSIONS Our results have shown that Ageratum conyzoides at 500 and 1000 mg/kg can induce liver, kidney and haematological disorders. These toxics effects can be attributed to its total alkaloids especially to pyrrolizidine alkaloids which are present in this plant.

Analysis of Adverse Reactions Related to Drugs and Vaccines Received at the National Centre for Pharmacovigilance from 2009 to 2016 in Togo

Objectives: To assess the received suspected adverse events occurring upon treatment with drugs and vaccines, at National Centre for Pharmacovigilance, in Togo, from 2009 to 2016. Methods: A crossover study was conducted in order to collect data about patients, drugs, suspected adverse events and notifiers. Suspected adverse events were classified using Med DRA 19.1. Notification’s circumstances were classified into Public Health Programs’ campaigns and routine practice. Data were collated into Excel spreadsheet and processed with SPSS software. Key Findings: Regional distribution is irregular. Of the 322 collected report forms, paramedics have notified 60.8% of the cases. Adult patients were the most represented (70.2%). Public Health Programs campaigns provided 72.6% versus 27.4% for routine practice including Neglected Tropical Diseases (41.4%), immunization (27.7%), tuberculosis (25.9%) and 4.5% for HIV. Skin disorders were the most prevalent suspected adverse events (147 sheets; 45.7%) followed by general disorders and administration site disorders (29.8%) and gastro-intestinal disorders (12.7%). General anti-infective drugs for systemic use, antiparasites, and insecticides were the most reported class of medications (161 sheets; 44.7%). Conclusions: A thorough follow-up of pharmacovigilance launched activities is needed to build a sustainable adverse effect’s surveillance system and routine practice has to be strengthened.