Site Of Biotransformation Research Articles

In Vitro-In Vivo Extrapolation of Hepatic Biotransformation Data for Fish. III.An In-depth Case Study with Pyrene.

Computational models that predict chemical bioaccumulation in fish generally account for biotransformation using an apparent first-order whole-body rate constant (kB ; d-1 ). The use of such models requires, therefore, that methods exist for estimating kB , ideally without the need to expose live animals. One promising approach for estimating kB involves the extrapolation of measured in vitro intrinsic clearance (CLIN VITRO,INT ) to the whole animal (in vitro-in vivo extrapolation, [IVIVE]). To date, however, the accuracy of such predictions has been difficult to assess due to uncertainties associated with one or more extrapolation factors and/or a mismatch between fish used to generate in vitro data and those used to conduct in vivo exposures. In the present study we employed a combined in vitro and in vivo experimental approach to evaluate the IVIVE procedure using pyrene (PYR) as a model chemical. To the extent possible, measured rates of CLIN VITRO,INT were extrapolated to estimates of kB using extrapolation factors based on measured values. In vitro material (liver S9 fraction) was obtained from fish exposed to PYR in a controlled bioconcentration study protocol. Fish from the same study were then used to estimate in vivo kB values from an analysis of chemical depuration data. Averaged across four study groups, kB values estimated by IVIVE underestimated those determined from in vivo data by 2.6-fold. This difference corresponds to a 4.1-fold underestimation of true in vivo intrinsic clearance, assuming the liver is the only site of biotransformation. These findings are consistent with previous work performed using mammals and have important implications for use of measured CLIN VITRO,INT values in bioaccumulation assessments with fish. Environ Toxicol Chem 2023;00:1-15. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Study of the Protective Effects of Benfotiamine Against CCl4-Induced Hepatotoxicity in Rats

Liver is considered as the first target for the toxic effects of toxins and other xenobiotics, and this can be attributed to its role as a site which receive all absorbed xenobiotics from the gastrointestinal tract and its role as a major site for biotransformation of xenobiotics. The present study was designed to evaluate the possible hepatoprotective effect of benfotiamine against CCl4-induced hepatotoxicity in rats. The study was conducted on 48 male albino rats; the animals were allocated into 8 groups (6 rats in each group) and treated as follow: 4 groups treated with oral doses of either normal saline, benfotiamine (100 mg/kg), thiamine (100 mg/kg), N-acetylcystein (400 mg/kg) only without induction of hepatic damage. The other 4 groups were treated as indicated previously with induction of hepatic damage with CCl4; at the end of treatment period, rats were scarified, blood samples obtained and livers excised for the assessment of the oxidative stress parameters (MDA and GSH), cholesterol and triglycerides levels. Additionally, serum levels of total bilirubin, albumin, total protein and the activities of ALT, AST and ALP enzymes were evaluated before and after treatment with benfotiamine. Tissue sections were prepared for evaluation of histopathological changes. The results indicated that benfotiamine has the ability to protect hepatic tissue against the toxicity induced by CCl4, revealed through reduction of serum levels of TSB and liver enzymes, decrease in the hepatic tissue MDA levels and elevation of GSH there. Histological evaluation of tissue sections prepared for this purpose confirmed the previous finding. In conclusion, benfotiamine is capable to protect liver tissue against CCl4-induced toxicity in rats more than thiamine.
 Key words: Benfotiamine, CCl4, Hepatotoxicity

Comparison of (6S)-5-methyltetrahydrofolic acidv.folic acid as the reference folate in longer-term human dietary intervention studies assessing the relative bioavailability of natural food folates: comparative changes in folate status following a 16-week placebo-controlled study in healthy adults

Folic acid (pteroylmonoglutamic acid) has historically been used as the reference folate in human intervention studies assessing the relative bioavailability of dietary folate. Recent studies using labelled folates indicated different plasma response kinetics to folic acid than to natural (food) folates, thus obviously precluding its use in single-dose experiments. Since differences in tissue distribution and site of biotransformation were hypothesised, the question is whether folic acid remains suitable as a reference folate for longer-term intervention studies, where the relative bioavailability of natural (food) folate is assessed based on changes in folate status. Healthy adults aged 18-65 years (n 163) completed a 16-week placebo-controlled intervention study in which the relative bioavailability of increased folate intake (453 nmol/d) from folate-rich foods was assessed by comparing changes in plasma and erythrocyte folate concentration with changes induced by an equal reference dose of supplemental (6S)-5-methyltetrahydrofolic acid or folic acid. The relative increase in plasma folate concentration in the food group was 31 % when compared with that induced by folic acid, but 39 % when compared with (6S)-5-methyltetrahydrofolic acid. The relative increase in erythrocyte folate concentration in the food group when compared with that induced by folic acid was 43 %, and 40 % when compared with (6S)-5-methyltetrahydrofolic acid. When recent published observations were additionally taken into account it was concluded that, in principle, folic acid should not be used as the reference folate when attempting to estimate relative natural (food) folate bioavailability in longer-term human intervention studies. Using (6S)-5-methyltetrahydrofolic acid as the reference folate would avoid future results' validity being questioned.

UTAB: a computer database on residues of xenobiotic organic chemicals and heavy metals in plants.

The UTAB Database contains information concerned with the uptake/accumulation, translocation, adhesion, and biotransformation of both xenobiotic organic chemicals and heavy metals by vascular plants. UTAB can be used to estimate the accumulation of chemicals in vegetation and their subsequent movement through the food chain. The database contains actual data from papers in the published literature dating from 1926 for organic chemicals and from 1976 for heavy metals. At present the database is comprised of more than 37,000 records pertaining to 900 different organic chemicals, 21 heavy metals, and over 350 plant species. Each record contains information on a single combination of species, chemical, and dose. Other information includes the application and destination sites, amount accumulated, rates of uptake or translocation, products and sites of biotransformation, experimental condition parameters, and the source paper. Thus, the database can be used to quickly obtain specific data pertaining to a chemical, plant species, mine spoil, etc. or it can be used for the comparative analysis of a set of data pertaining to groups of chemicals and plants.