Moustapha Ouedraogo

Protective effect of Moringa oleifera leaves against gentamicin-induced nephrotoxicity in rabbits.

Oxidative stress due to abnormal production of reactive oxygen species has been implicated in the nephrotoxicity induced by gentamicin. The nephroprotective effect of aqueous-ethanolic extract of Moringa oleifera leaves (150 and 300 mg/kg) was evaluated against gentamicin-induced (80 mg/kg) renal injury in rabbits. Serum urea and creatinine levels were evaluated as the markers of renal nephrotoxicity. At the end of the experiment, the kidneys of rabbits were excised for histological examinations and determination of lipid peroxidation levels. Serum urea and creatinine levels were reduced in the M. oleifera (150 and 300 mg/kg) plus gentamicin treated groups. On histological examinations, kidney of intoxicated rabbits groups which received M. oleifera extract showed reparative tendencies. A highly significant (p < 0.01) elevation was observed in lipid peroxidation (LPO) level in the kidneys of gentamicin-intoxicated rabbits whereas combined treatment of M. oleifera and gentamicin group showed a highly significant (p < 0.01) depletion in LPO. The present study indicates that aqueous-ethanolic extract of M. oleifera leaves attenuates renal injury in rabbits treated with gentamicin, possibly by inhibiting lipid peroxidation.

Methods Applied to the In Vitro Primary Toxicology Testing of Natural Products: State of the Art, Strengths, and Limits

The present review attempts to build up a comprehensive picture of the major primary techniques used to screen and assess the cytotoxicity of plant complex mixtures. These can be based on metabolic activity, on membrane integrity, on morphological features, on cell growth; the type of cell death can also be established from more or less specific events (e.g., apoptosis, autophagy, DNA damage detection, reactive oxygen species involvement). This review will discuss the benefits, the difficulties, and the challenges that may occur along cytotoxicity testing of raw extracts and isolated natural compounds.

An Overview of Cancer Chemopreventive Potential and Safety of Proanthocyanidins

Cancer is a major public health problem worldwide. Over two-thirds of cancer-related deaths could most probably be prevented through lifestyle modification, particularly through dietary means. Proanthocyanidins (PAs), the most abundant polyphenolic substances after lignin in the plant kingdom, have been widely investigated for their chemopreventive potential. The PAs literature has, however, been mostly concerned with positive cardiovascular activities, and recent reviews about cancer chemoprevention are scarce. The present review highlights a series of in vitro and in vivo studies indicating (1) that PAs can act as anticarcinogenic agents through their antioxidant, apoptosis-inducing, immuno-modulating, and/or enzyme modulating properties, effects on epigenetics; and (2) that PAs could be particularly safe dietary compounds. These convergent data encourage further research to better understand the many aspects of cancer chemoprevention by PAs.

Potential genotoxicity of traditional chinese medicinal plants and phytochemicals: an overview.

In the last decades, cases of poisoning due to herbal medicines have occurred in many countries; Chinese herbal medicines (CHMs) are occasionally involved. The experience gained from traditional use is efficient to detect immediate or near‐immediate relationship between administration and toxic effects but is quite unlikely to detect medium‐ to long‐term toxicities; thorough investigations of herbal medicines (toxicity assessments, active pharmacovigilance) appear then essential for their safe use. Genotoxicity is an especially insidious toxicity that may result in carcinoma development years after exposure; it can arise from multiple compounds, with or without metabolic activation. The present work reviews traditional CHMs and phytochemicals that have been shown to present a genotoxic hazard. Copyright

Effects of chemopreventive natural products on non-homologous end-joining DNA double-strand break repair.

Double-strand breaks (DSBs) may result from endogenous (e.g., reactive oxygen species, variable (diversity) joining, meiotic exchanges, collapsed replication forks, nucleases) or exogenous (e.g., ionizing radiation, chemotherapeutic agents, radiomimetic compounds) events. DSBs disrupt the integrity of DNA and failed or improper DSBs repair may lead to genomic instability and, eventually, mutations, cancer, or cell death. Non-homologous end-joining (NHEJ) is the major pathway used by higher eukaryotic cells to repair these lesions. Given the complexity of NHEJ and the number of proteins and cofactors involved, secondary metabolites from medicinal or food plants might interfere with the process, activating or inhibiting repair. Twelve natural products, arbutin, curcumin, indole-3-carbinol, and nine flavonoids (apigenin, baicalein, chalcone, epicatechin, genistein, myricetin, naringenin, quercetin, sakuranetin) were chosen for their postulated roles in cancer chemoprevention and/or treatment. The effects of these compounds on NHEJ were investigated with an in vitro protocol based on plasmid substrates. Plasmids were linearized by a restriction enzyme, generating cohesive ends, or by a combination of enzymes, generating incompatible ends; plasmids were then incubated with a nuclear extract prepared from normal human small-intestinal cells (FHS 74 Int), either treated with these natural products or untreated (controls). The NHEJ repair complex from nuclear extracts ligates linearized plasmids, resulting in plasmid oligomers that can be separated and quantified by on-chip microelectrophoresis. Some compounds (chalcone, epicatechin, myricetin, sakuranetin and arbutin) clearly activated NHEJ, whereas others (apigenin, baicalein and curcumin) significantly reduced the repair rate of both types of plasmid substrates. Although this in vitro protocol is only partly representative of the in vivo situation, the natural products appear to interfere with NHEJ repair and warrant further investigation.

Biological alterations and self-reported symptoms among insecticides-exposed workers in Burkina Faso

Biological alterations and self-reported symptoms among insecticides-exposed workers in Burkina Faso Occupationally exposed workers, farm workers and plant protection agents in the Sahel region of Burkina Faso were interviewed to assess adverse health effects of insecticides. The subjects were also examined for changes in both hematological and biochemical parameters. The prevalence of liver and kidney dysfunction was found to be quite high among insecticide applicators, especially among plant protection agents. The prevalence of biochemical alterations seems to be correlated to the frequency of insecticide use. However, no significant differences were found between the hematological parameters among farm workers and plant protection agents. The hematological parameters of all the insecticide applicators were normal. The great majority of insecticide applicators (85%) reported symptoms related to insecticide exposure. The use of insecticides in the agriculture of Burkina Faso is threatening to human health.

Effect of hydroxyapatite on the physicochemical characteristics of a gentamicin-loaded monoolein gel intended to treat chronic osteomyelitis.

Many works have demonstrated the real potential of gentamicin-monoolein-water formulations as bioresorbable and sustained-release implants for the local treatment of the chronic osteomyelitis. In order to improve the efficacy of this type of implant, the incorporation of hydroxyapatite, a well-known osteointegrator material, is thought to be an interesting approach. Five formulations incorporating 0, 2.5, 5, 10, and 20% of hydroxyapatite were examined with regard to their physicochemical and in vitro drug release characteristics. The rheological, thermal (differential scanning calorimetric and thermogravimetric diffraction analysis), X-ray diffraction, and dissolution studies have showed that the presence of hydroxyapatite does not dramatically disturb the cubic liquid crystalline structure of the monoolein-water gel and their ability to progressively release the antibiotic. Implant 20% that was capable to release gentamicin sulfate over a period of four weeks without marked burst effect could be used as a more suitable biodegradable delivery system for the local management of chronic osteomyelitis.

Partial Chemical Characterization of Immunomodulatory Polysaccharides from Plantago palmata Hook. f. s. Leaves

A previous work on Plantago palmata polysaccharides (PS) attributed immunomodulatory properties of leaves to a polysaccharide fraction (PS50) that stimulated NO and TNF-α production by interferon gamma- (IFN-γ-) activated macrophages. The present work aims to elucidate the chemical structure of these immunomodulatory polysaccharides. Size exclusion chromatography showed that the active polymers present an active fraction with a very high molecular weight (about 1200 kDa). These polysaccharides are pectic in nature, with a predominantly unbranched galacturonan domain and with a domain bearing side chains that consist of highly branched arabinan, galactan, and/or arabinogalactan. Comparatively to the well-known Plantago major biologically active PS, Plantago palmata PS50 contained less arabinogalactan-proteins (AGPs) and had a different composition in glucose, galactose, and galacturonic acid. DNA contamination of the polysaccharide was estimated at about 0.04%, a concentration much lower than those reported immunomodulatory in hyaluronic acid preparations (3 to 15%). Therefore, the eventuality of a contaminating DNA-mediated biological activity could be ruled out.

On-chip microelectrophoresis for the study of in vitro nonhomologous end-joining DNA double-strand break repair.

Oligomerization of linearized plasmids by nuclear proteins extracts, a recognized measure of nonhomologous end-joining (NHEJ) repair capacity, is typically assessed through agarose gel electrophoresis, a labor-intensive procedure. In the current study, a more convenient NHEJ assay was developed using microchips that allow scaled-down separation and quantification. This microchip method allows a considerable reduction in sample amount and analysis time with similar costs and comparable or slightly better precision. Data obtained with quercetin and wortmannin show that the method can be applied to the screening of food components and natural products for positive and negative modulators of NHEJ, potential chemopreventive and indirect genotoxic compounds, respectively.

Synthesis and plasma pharmacokinetics in CD-1 mice of a 18β-glycyrrhetinic acid derivative displaying anti-cancer activity

The plasma pharmacokinetic profile in CD‐1 mice of a novel 18β‐glycyrrhetinic acid (GA) derivative, which displays in vitro anti‐cancer activity, was assessed.