PubMed · 1733579
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C R Paterson, K I Naismith, J A Young. 1992. Severe unexplained hypophosphatemia.. https://pubmed.ncbi.nlm.nih.gov/1733579/
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When toxicants cause effects to aquatic organisms, it is often unclear by what route, or routes, the toxicant entered the affected organism. The toxicity of a compound depends on its degree of uptake, distribution and metabolism, as well as its molecular interactions at the site of action. It was hypothesised, that a hydrophobic chemical such as 4-tert-nonylphenol (4-NP), entering via the gills/skin, may be more oestrogenic than one entering through the diet, because in the latter case it will undergo metabolism in the small intestine and liver before entering the bloodstream. In this way, metabolism may reduce or eliminate the oestrogenic potential of 4-NP before it reaches target organs such as the gonads or liver. To compare the potency of 4-tert-nonylphenol when administered via different routes, male fathead minnows (Pimephales promelas) were exposed to 4-NP either through waterborne exposure (experiment 1), or via the diet (experiment 2). Fish were exposed to 4-NP for 2 weeks either via the water at one of three nominal concentrations: 1, 10 or 50 microg/l (experiment 1) or 100, 500 or 1000 microg/day via the diet (experiment 2). Liver and blood samples were taken for vitellogenin mRNA and plasma vitellogenin quantification, respectively. Exposure of male fathead minnows to 50 microg/l of 4-NP in the water (experiment 1) and 500 and 1000 microg/day of 4-NP via the diet (experiment 2) induced vitellogenin mRNA. A similar pattern occurred for plasma vitellogenin induction, however, there was also a significant increase in plasma vitellogenin concentration in the fish exposed via the water to 10 microg/l of 4-NP. Using data from pharmacokinetics studies, an estimate for the total amount of 4-NP that entered the fish during each exposure was compared with the concentrations of plasma vitellogenin in each group of fish. The result showed a 10-fold greater sensitivity for 4-NP in fish exposed via the water compared with exposure via the oral route.Results obtained from this study indicate that a chemical such as 4-NP has a higher oestrogenic potential when it enters the bloodstream via the gills/skin of a fish compared with exposure through the diet.
Hydroxycinnamic acids are a group of phenolic compounds that exhibit a wide range of in vitro chemoprotective and antioxidant properties. Cereals containing a high proportion of the bran layers are rich in ester-linked hydroxycinnamic acids, such as ferulic and diferulic acids. The present work investigated the absorption in humans of hydroxycinnamic acids from high-bran breakfast cereal (wheat). Plasma and urine samples from six volunteers were collected before and after cereal consumption and analyzed for total hydroxycinnamic acids content after beta-glucuronidase/sulfatase treatment both by HPLC-DAD and by LC-MS (SIM monitoring). High-bran cereal administration resulted in increased plasma ferulic and sinapic acid concentrations (maximum levels detected of approximately 200 and approximately 40 nM, respectively) with absorption peaks between 1 and 3 h. Increases of approximately 4-fold in ferulic acid and approximately 5-fold in feruloylglycine were detected in 24-h urine after consumption of the cereal. Most of the ferulic acid detected in urine and plasma was present as conjugates (feruloylglycine and/or glucuronides). Diferulic acids were undetectable. The data show that ferulic and sinapic acids are taken up in humans from dietary high bran wheat but that absorption is limited and may originate only from the free and soluble portions present in the cereal.
Toxicokinetic behavior and metabolism studies of metamitron and its effect on the cytochrome P(450) content of liver microsomal pellet were carried out in black Bengal goats after a single oral administration at 278 mg kg(-1) and consecutive oral administration of 30 mg kg(-1) for 7 days. Metamitron was detected in the blood sample at 0.08 h (12.0 +/- 0.87 microg mL(-1)), maximum at 4 h (84.3 +/- 8.60 microg mL(-1)) and minimum (14.6 +/- 1.67 microg mL(-1)) at 36 h blood sample after a single oral administration. The absorption rate constant was 0.69 +/- 0.09 h(-1). The Vd(area) (2.00 +/- 0.08 L kg(-1)) and t(1/2)beta (8.98 +/- 0.70 h) values suggested wide distribution and long persistence of the compound in the body. The values of T approximately B (0.80 +/- 0.04), F(c) (0.55 +/- 0.01), Cl(B) (0.15 +/- 0.00 L kg(-1) h(-1)), and K(21) (0.41 +/- 0.03 h(-1)) suggested that metamitron retained in the blood compared to that in the tissue. Maximum concentration of metamitron residue was found in the adrenal gland followed by bile on day 4 of single oral administration. The higher Cl(R) compared to Cl(H) value indicated the excretion of the major portion (34-40%) through urine compared to feces (20-26%). Maximum concentrations of metamitron and its metabolite, deaminometamitron, were excreted through urine and feces at 48 and 24 h samples, respectively. The recovery of metamitron including its metabolite in terms of parent compound varied from 69.3 to 80.1%, of which contribution of metabolite in terms of parent compound varied from 53.1 to 63.0%. Repeated oral administration of metamitron at 30 mg kg(-1) for 7 days caused induction of the cytochrome P(450) content of liver microsomal pellet of goat, suggesting oxidative deamination of metamitron.