Toxicology
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Long-term exposure to isoflurane may induce long-term developmental neurotoxicity and cognitive impairments in the neonatal brains. Trilobatin, a leaf extract from the Chinese traditional sweet tea Lithocarpus polystachyus Rehd, possesses various biological properties including anti-inflammatory and anti-oxidant properties. Our study aimed to explore the neuroprotective effect of trilobatin on isoflurane-induced neurotoxicity in mouse hippocampal neuronal HT22 cells. ⋯ Additionally, trilobatin promoted the nuclear translocation of Nrf2 as well as the mRNA and protein expression of HO-1 and NQO1 in HT22 cells exposed to isoflurane. Nrf2 knockdown attenuated the effects of trilobatin on isoflurane-induced viability reduction, LDH release, apoptosis, and oxidative stress in HT22 cells. Overall, trilobatin protected HT22 cells against isoflurane-induced neurotoxicity via activating the Nrf2/antioxidant response element (ARE) pathway.
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Neurotoxic effects of high-level occupational exposure to manganese (Mn) are well established; however, whether lower-level environmental exposure to Mn in early life causes neurodevelopmental toxicity in children is unclear. ⋯ The statistical associations reported in the few studies of specific Mn biomarkers and specific neurodevelopmental endpoints do not establish causal effects based on the Bradford Hill considerations. Additional prospective cohort studies of Mn biomarkers and validated neurodevelopmental outcomes, and a better understanding of the etiologic relevance of Mn biomarkers, are needed to shed light on whether environmental exposure to Mn causes adverse neurodevelopmental effects in children.
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Review
A review of the genotoxic, mutagenic, and carcinogenic potentials of several lower acrylates.
Lower alkyl acrylate monomers include methyl-, ethyl-, n-butyl-, and 2-ethylhexyl acrylate. These acrylates are used in the manufacture of acrylic polymers and copolymers for plastics, food packaging, adhesives, and cosmetic formulations. Although there is limited potential for human environmental exposure, occupational exposure can occur via inhalation and dermal contact. ⋯ At high doses, and secondary to chronic site-of-contact irritation and corrosion, rodent forestomach tumors were induced by oral gavage dosing with ethyl acrylate, and skin tumors were observed following chronic dermal dosing with 2-ethylhexyl acrylate in C3H/HeJ inbred mice (a strain with deficiencies in wound healing), but not in the outbred NMRI strain. For both dermal and forestomach cancers, tumorigenesis is secondary to high doses and long-term tissue damage, shown to be reversible. With evidence that these chemicals are not genotoxic, and that they cause forestomach and dermal tumors through chronic irritation and regenerative proliferation mechanisms, these acrylates are unlikely to pose a human cancer hazard.
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Comparative Study
Acute administration of tramadol and tapentadol at effective analgesic and maximum tolerated doses causes hepato- and nephrotoxic effects in Wistar rats.
Tramadol and tapentadol are two atypical synthetic opioid analgesics, with monoamine reuptake inhibition properties. Mainly aimed at the treatment of moderate to severe pain, these drugs are extensively prescribed for multiple clinical applications. Along with the increase in their use, there has been an increment in their abuse, and consequently in the reported number of adverse reactions and intoxications. ⋯ Histopathological findings included sinusoidal dilatation, microsteatosis, vacuolization, cell infiltrates and cell degeneration, indicating metabolic changes, inflammation and cell damage. In conclusion, a single effective analgesic dose or the maximum recommended daily dose of both opioids leads to hepatotoxicity and nephrotoxicity, with tapentadol inducing comparatively more toxicity. Whether these effects reflect risks during the therapeutic use or human overdoses requires focused attention by the medical community.