Oxidative stress in normal hematopoietic stem cells and leukemia.

Leukemia is developed following the abnormal proliferation of immature hematopoietic cells in the blood when hematopoietic stem cells lose the ability to turn into mature cells at different stages of maturation and differentiation. Leukemia initiating cells are specifically dependent upon the suppression of oxidative stress in the hypoglycemic bone marrow (BM) environment to be able to start their activities. Relevant literature was identified by a PubMed search (2000-2017) of English-language literature using the terms 'oxidative stress,' 'reactive oxygen species,' 'hematopoietic stem cell,' and 'leukemia.' The generation and degradation of free radicals is a main component of the metabolism in aerobic organisms. A certain level of ROS is required for proper cellular function, but values outside this range will result in oxidative stress (OS). Long-term overactivity of reactive oxygen species (ROS) has harmful effects on the function of cells and their vital macromolecules, including the transformation of proteins into autoantigens and increased degradation of protein/DNA, which eventually leads to the change in pathways involved in the development of cancer and several other disorders. According to the metabolic disorders of cancer, the relationship between OS changes, the viability of cancer cells, and their response to chemotherapeutic agents affecting this pathway are undeniable. Recently, studies have been conducted to determine the effect of herbal agents and cancer chemotherapy drugs on oxidative stress pathways. By emphasizing the role of oxidative stress on stem cells in the incidence of leukemia, this paper attempts to state and summarize this subject.

Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in suppression of respiratory inflammation: a comparison with ibuprofen.

In this study, combinations of Ginkgo biloba leaf extract (EGb761) plus the carotenoid antioxidant astaxanthin (ASX) and vitamin C were evaluated for a summative dose effect in the inhibition of asthma-associated inflammation in asthmatic guinea-pigs. Ovalbumin-sensitized Hartley guinea-pigs challenged with ovalbumin aerosol to induce asthma, were administered EGb761, ASX, vitamin C or ibuprofen. Following killing, bronchoalveolar lavage (BAL) fluid was evaluated for inflammatory cell infiltrates and lung tissue cyclic nucleotide content. Each parameter measured was significantly altered to a greater degree by drug combinations, than by each component acting independently. An optimal combination was identified that included astaxanthin (10 mg/kg), vitamin C (200 mg/kg) and EGb761 (10 mg/kg), resulting in counts of eosinophils and neutrophils each 1.6-fold lower; macrophages 1.8-fold lower, cAMP 1.4-fold higher; and cGMP 2.04-fold higher than levels in untreated, asthmatic animals (p < 0.05). In conclusion, EGb761, ASX and vitamin C are shown here to interact summatively to suppress inflammation with efficacy equal to or better than ibuprofen, a widely used non-steroidal antiinflammatory drug (NSAID). Such combinations of non-toxic phytochemicals constitute powerful tools for the prevention of onset of acute and chronic inflammatory disease if consumed regularly by healthy individuals; and may also augment the effectiveness of therapy for those with established illness.

Study of the mutagenicity of "Hypiran" and "Sankol" in human blood cells and comparison with hydrogen peroxide by single cell gel electrophoresis (SCGE) or comet assay.

Due to the increased use and availability of herbal medicinal products, it has been necessary to perform investigations pertaining to their toxicological safety. The aim of this study was to use the rapid and sensitive technique of Single Cell Gel Electrophoresis (SCGE) or "Comet Assay" to assess the mutagenic potential of two such products: "Hypiran" and "Sankol." The results were compared against positive (hydrogen peroxide) and negative (no mutagen) control groups. The instances of DNA damage were observed in 25 randomly selected cells and viewed under a fluorescence microscope following electrophoresis and staining with ethidium bromide. Both microscopic inspection and calculation of the number of affected/damaged cells were encouraging and were comparable to the observations of previous studies using SCGE. The total instances of cell damage in the presence of "Hypiran" increased as the dose increased, with all 25 cells exhibiting fragmentation at the highest dose. However, "Sankol" only exhibited some damage (8-12% of cells) at all doses. The results obtained suggest that in vitro, "Hypiran" produces dose dependent DNA damage and therefore may possess some mutagenic potential. Compared to the positive control, no significant DNA damage was observed with "Sankol" and hence this compound may have no mutagenic potential. However, further study is required before a full evaluation of these products can be made.