Archives of toxicology
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Archives of toxicology · Sep 2016
ReviewFollow-up studies on genome damage in children after Chernobyl nuclear power plant accident.
As children are more susceptible to ionizing radiation than adults, each nuclear accident demands special attention and care of this vulnerable population. The Chernobyl nuclear disaster occurred in a region populated with a large number of children, but despite all efforts and expertise of nuclear specialists, it was not possible to avoid casualties. As vast regions of Ukraine, Belarus and Russia were exposed to doses of ionizing radiation, which are known to be related with different diseases, shortly after the accident medical surveillance was launched, which also included analysis of genome damage. ⋯ Genome instability and radiosensitivity in children was detected both in evacuated and continuously exposed children. Today the population exposed to ionizing radiation in 1986 is in reproductive period of life and follow-up of this population and their offspring is of great importance. This review aims to give insight in results of studies, which reported genome damage in children in journals without language restrictions.
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Archives of toxicology · May 2016
CCR5 deficiency increased susceptibility to lipopolysaccharide-induced acute renal injury.
C-C chemokine receptor 5 (CCR5) regulates leukocyte chemotaxis and activation, and its deficiency exacerbates development of nephritis. Therefore, we investigated the role of CCR5 during lipopolysaccharide (LPS)-induced acute kidney injury. CCR5-deficient (CCR5-/-) and wild-type (CCR5+/+) mice, both aged about 10 months, had acute renal injury induced by intraperitoneal injection of LPS (10 mg/kg). ⋯ Moreover, primary kidney cells from CCR5-/- mice showed greater increases in TNF-α production and p38 MAP kinase activation following treatment with LPS compared with that observed in the cells from CCR5+/+ mice. LPS-induced TNF-α production and apoptosis in the primary kidney cells from CCR5-/- mice were inhibited by treatment with p38 MAP kinase inhibitor. These results suggest that CCR5 deficiency increased the production of TNF-α following LPS treatment through increased activation of the p38 pathway in the kidney, resulting in renal apoptosis and leukocyte infiltration and led to exacerbation of LPS-induced acute kidney injury.
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Archives of toxicology · Mar 2016
Polyhexamethylene guanidine phosphate aerosol particles induce pulmonary inflammatory and fibrotic responses.
Polyhexamethylene guanidine (PHMG) phosphate was used as a disinfectant for the prevention of microorganism growth in humidifiers, without recognizing that a change of exposure route might cause significant health effects. Epidemiological studies reported that the use of humidifier disinfectant containing PHMG-phosphate can provoke pulmonary fibrosis. However, the pulmonary toxicity of PHMG-phosphate aerosol particles is unknown yet. ⋯ All features of fibrogenesis by PHMG-phosphate aerosol particles closely resembled the pathology of fibrosis that was reported in epidemiological studies. Finally, we expected that PHMG-phosphate infiltrated into the lungs in the form of aerosol particles would induce an airway barrier injury via ROS, release fibrotic inflammatory cytokines, and trigger a wound-healing response, leading to pulmonary fibrosis. A simultaneous state of tissue destruction and inflammation caused by PHMG-phosphate had whipped up a "perfect storm" in the respiratory tract.
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Archives of toxicology · Jan 2016
Roles of microRNA-1 in hypoxia-induced apoptotic insults to neuronal cells.
Hypoxia is a common occurrence in brain tumors and traumatic brain injury. microRNA (miR)-1 participates in the regulation of brain development and neuronal function. Interestingly, miR-1 can mediate ischemia-induced injury to cardiomyocytes. This study was designed to evaluate the roles of miR-1 in hypoxia-induced insults to neurons and the possible mechanisms. ⋯ In comparison, knocking down miR-1 expression synergistically enhanced OGD-induced HSP-70 mRNA. As to the mechanism, reducing miR-1 expression lowered OGD-induced alterations in the MMP, caspase-3 activation, DNA fragmentation, and cell apoptosis. Taken together, this study shows that miR-1 can target HSP-70 expression and consequently mediate hypoxia-induced apoptotic insults to neuro-2a cells via an intrinsic Bax-mitochondrion-caspase protease pathway.