Sprague-Dawley rats were exposed to aerosols of one of three base stocks used to formulate lubricating oils. These stocks were a solvent-refined oil (SRO), a hydrotreated and acid-washed white oil (WTO) and a severely hydrotreated and hydrocracked oil (HBO). Exposures were for 6 h per day, 5 days per week for ca. 4 weeks. There were four groups of rats for each study (10 per sex per group). Aerosol concentrations were ca. 0, 50, 210 and 1000 mg m-3 for each material; the mass median aerodynamic diameter was ca. 1 microns. Following the last exposure, all animals were sacrificed and necropsied. Samples were taken for serum chemistry, hematology, sperm morphology, weights of seven organs and histopathology on at least nine organs. Body weights and clinical signs were not affected by exposures. The only treatment-related changes were in the lung and associated lymph nodes. Both the wet weight of the lung and the dry/wet weight ratio increased in a concentration-related manner. Associated with the increased weight were accumulations of foamy alveolar macrophages, particularly in alveoli close to alveolar ducts. Mild infiltration by neutrophils was observed with WTO and SRO; thickened alveolar walls were noted with the highest concentration of HBO. These mild responses to exposures at very high concentrations indicate a low degree of toxicity for these aerosols.
As a well known anti-neoplastic drug, the cytogenotoxicity of methotrexate (MTX) has received more attention in recent years. To develop a new cytoprotector to reduce the risk of second cancers caused by methotrexate, an umu test combined with a micronucleus assay was employed to estimate the cytoprotective effects of ten kinds of bioactive phytochemicals and their combinations. The results showed that allicin, proanthocyanidins, polyphenols, eleutherosides and isoflavones had higher antimutagenic activities than other phytochemicals. At the highest dose tested, the MTX genetoxicity was suppressed by 34.03%∼67.12%. Of all the bioactive phytochemical combinations, the combination of grape seed proanthocyanidins and eleutherosides from Siberian ginseng as well as green tea polyphenols and eleutherosides exhibited stronger antimutagenic effects; the inhibition rate of methotrexate-induced genotoxicity separately reached 74.7 ± 6.5% and 71.8 ± 4.7%. Pretreatment of Kunming mice with phytochemical combinations revealed an obvious reduction in micronucleus and sperm abnormality rates following exposure to MTX (p < 0.01). Moreover, significant increases in thymus and spleen indices were observed in cytoprotector candidates in treated groups. The results indicated that bioactive phytochemicals combinations had the potential to be used as new cytoprotectors.
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