RESUMO
BACKGROUND/AIMS: Most pesticide formulations contain both chief and additive ingredients. But, the additives may not have been tested as thoroughly as the chief ingredients. The surfactant, nonyl phenoxypolyethoxylethanol (NP40), is an additive frequently present in pesticide formulations. We investigated the effects of NP40 and other constituents of a validamycin pesticide formulation on cell viability and on the expression of genes involved in cell damage pathways. METHODS: The effects of validamycin pesticide ingredients on cell viability and of NP40 on the mRNA expression of 80 genes involved in nine key cellular pathways were examined in the human neuroblastoma SK-N-SH cell line. RESULTS: The chemicals present in the validamycin pesticide formulation were cytotoxic to SK-N-SH cells and NP40 showed the greatest cytotoxicity. A range of gene expression changes were identified, with both up- and down-regulation of genes within the same pathway. However, all genes tested in the necrosis signaling pathway were down-regulated and all genes tested in the cell cycle checkpoint/arrest pathway were up-regulated. The median fold-change in gene expression was significantly higher in the cell cycle checkpoint/arrest pathway than in the hypoxia pathway category (p = 0.0064). The 70 kDa heat shock protein 4 gene, within the heat shock protein/unfolded protein response category, showed the highest individual increase in expression (26.1-fold). CONCLUSIONS: NP40 appeared to be particularly harmful, inducing gene expression changes that indicated genotoxicity, activation of the cell death (necrosis signaling) pathway, and induction of the 70 kDa heat shock protein 4 gene.
Assuntos
Inositol/análogos & derivados , Neurônios/efeitos dos fármacos , Nonoxinol/toxicidade , Praguicidas/intoxicação , Tensoativos/toxicidade , Idoso , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Genes cdc , Proteínas de Choque Térmico HSP110/genética , Proteínas de Choque Térmico HSP110/metabolismo , Humanos , Inositol/química , Inositol/intoxicação , Necrose , Neurônios/metabolismo , Neurônios/patologia , Nonoxinol/química , Praguicidas/química , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tensoativos/químicaRESUMO
Renal failure caused by scrub typhus is known to be reversible. In most cases, renal function is almost fully restored after appropriate antibiotic treatment. A 71-year-old man was diagnosed with scrub typhus complicated by renal failure. A renal biopsy revealed histopathologic findings consistent with acute tubulointerstitial nephritis. Renal function did not improve 18 months after discharge and the patient required continuous hemodialysis. Although severe renal failure requiring dialysis is a rare complication of scrub typhus, we describe a case of scrub typhus requiring maintenance hemodialysis. To the best of our knowledge, this is the first such report.