RESUMO
The Alternaria toxins alternariol (AOH) and alternariol monomethyl ether (AME) have been reported previously to act as activators of the aryl hydrocarbon receptor (AhR) in murine hepatoma cells, thus enhancing the expression of cytochrome P450 (CYP) 1A monooxygenases. Concomitantly, both benzopyrones represent substrates of CYP1A, giving rise to catecholic metabolites. The impact of AOH and AME on CYP1A expression in human cells of different tissue origin colon (HT29), esophagus (KYSE510), liver (HepG2) and their effects on cell viability, generation of reactive oxygen species (ROS) and DNA integrity were investigated. ROS production was induced by both mycotoxins in all cell lines with AOH exhibiting the highest potency in esophageal cells concomitant with the most prominent CYP1A induction level. Of note, altertoxin-II (ATX-II), the more potent DNA-damaging mutagen formed by Alternaria alternata, induces CYP1A even at significant lower concentrations. AhR-siRNA knockdown in human esophageal cells supported the hypothesis of AhR-mediated CYP1A1 induction by AOH. However, DNA damage was minor at CYP1A1-inducing AOH concentrations. AhR-depletion did not affect the DNA-damaging properties of AOH indicating no substantial impact of AhR in this regard. However, in combination with xenobiotics prone to metabolic activation by CYP1A the induction of CYP1A by Alternaria toxins deserves further attention.
Assuntos
Alternaria/metabolismo , Citocromo P-450 CYP1A1/genética , Dano ao DNA/efeitos dos fármacos , Micotoxinas/toxicidade , Benzo(a)Antracenos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Citocromo P-450 CYP1A1/metabolismo , Regulação da Expressão Gênica , Células HT29 , Células Hep G2 , Humanos , Lactonas/toxicidade , Espécies Reativas de Oxigênio , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismoRESUMO
The methods of continuous (C) and intermittent (I) nasogastric tube feedings in 60 patients, 54 men and 6 women, with a mean age of 72 +/- 9 years were compared in terms of number of complications, staff time used, and caloric intake. Patients were randomly assigned between these two methods and followed for 7 days. Diarrhea, aspiration pneumonia, clogged tubes, and self-extubation were observed in both groups. Diarrhea was significantly more frequent (96% of 30 patients) in the I group than the C group (66% of 30 patients) (p < .008). Furthermore, diarrhea was more prolonged (4 days or more) in 64% of 30 patients in the I group than the C group (4 days or more) in 58% of 30 patients (p < .02). However, clogged tubes occurred 3 times more often in the C group (p < .01). Self-extubation and aspiration pneumonia tend to be more frequent in the I group but the difference was not significant. The average time used by staff nurses in the maintenance of NGT feedings was not significantly longer in the I group (48.45 +/- 11 min/patient per day) than the C group (46.46 +/- 11 min/patient per day). In the C group the mean calories recommended were 2248 +/- 36 kcal/day but the actual caloric intake was only 1465 +/- 281 kcal/day, a deficiency of 783 +/- 291 kcal/day. The recommended calorie count for the I group was 2021 +/- 5 kcal/day but the amount delivered was only 1226 +/- 254 kcal/day, which resulted in a deficit of 795 +/- 259 kcal/day.(ABSTRACT TRUNCATED AT 250 WORDS)