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Rapeseed oil fed to male weanling rats as 15% by weight of the diet for 2 months does not influence the plasma content of triglycerides (TG), phospholipids (PL), nonesterified fatty acids (NEFA) and cholesterol esters (CE), as compared to peanut oil and canbra oil (‘zero erucic acid’ rapeseed oil). However, the fatty acid spectra are changed: erucic acid and eicosénoïque acid from dietary rapeseed oil are mainly incorporated in TG and NEFA, less in PL and practically not at all in CE. Feeding time has little effect. Therefore, the immediate but temporary cardiac steatosis which is obtained in weanling rats fed rapeseed oil cannot be explained by modifications of the plasma TG or NEFA concentration and/or their fatty acid composition. Rapeseed and canbra oil increase the percentages of ω3-polyunsaturated fatty acids and of nervonic acid in plasma PL.

A rapid and sensitive high performance liquid chromatographic method for the determination of trace amounts of chloramphenicol (CP) in milk has been developed. The antibiotic can be quantitated at a 10 ppb level with a limit of detectability estimated at 5 ppb. Recoveries ranged from 72 to 99.5%. Milking studies have been carried out on goats that received CP either by intramuscular injection or by intramammary administration. CP was measured in milk samples collected 1, 2, 3, 4, 5, 6, 7, 8, 24, 32 h after treatments. No residue could be detected 32 h after treatment. No interfering peaks appeared on control milk chromatograms.

Among the urinary metabolites of dodecylcyclohexane or cyclohexylacetic acid, the glycine conjugate of 1-hydroxy-cyclohexylacetic acid was identified and its origin studied, using cyclohexylacetic acid as the starting molecule, as it results from beta-oxidation of cyclohexyldodecanoic acid produced by terminal oxidation of the alkyl chain of the cycloparaffin. Three hypotheses were tested: (a) hydroxylation by the liver microsomal mixed-function oxidases involved in detoxication mechanisms; (b) hydroxylation by a cyt. P450-containing mitochondrial hydroxylase; and (c) beta-oxidation blockade after the reaction catalyzed by enoyl-CoA-hydratase. Liver microsomal or mitochondrial fractions were prepared and incubated in the presence of [14C] cyclohexylacetic acid, glucose-6-phosphate dehydrogenase and a NADPH-producing system. On the other hand, mitochondria were incubated in a suitable respiratory medium with or without cofactors required for ATP production. The reaction products were extracted and analyzed by thin layer radiochromatography and radio gas chromatography. Evidence is given that hydroxylation of cyclohexylacetic acid in position 1 is a mitochondrial step requiring activation in the acyl-CoA form and results from beta-oxidation blockade, the cyclohexane ring hindering hydroxyacyl-CoA-dehydrogenase action.

The action of gut microflora on the metabolism of chloramphenicol (CP) was studied in germfree (GF) and conventional (CV) rats after administration of single oral doses of tritiated CP. There were similarities in the metabolic pathways of CP in the GF and CV animals, i.e., rapid absorption, hepatic glucuroconjugation, and biliary excretion of the CP conjugate. CP, CP-oxamic acid, CP-alcohol, and CPbase were present in similar proportions in the urine of both GF and CV rats. Differences observed included the slow elimination of total radioactivity and a reduced proportion of the urinary excretion versus the fecal excretion in the GF rats and' different patterns of urinary and fecal metabolites for the two groups. Reduction products which were present in much greater quantities in the urine and feces of CV rats are compatible with the generally described hydrolysis of the CP-glucuronide, followed by a nitroreduction of the CP by the gut microflora and the reabsorption of a part of the products formed. In GF rats, CP-glucuronide was the major fecal metabolite, a portion of it having been reabsorbed and excreted in the urine. Although in lesser amounts, reduction products were still present as urinary metabolites in GF rats. Such a reduction in the tissues might produce active intermediate that could be related to CP toxicity.Chloramphenicol (CP) is one of the oldest and most potent antibiotics, but its use is limited because of its toxic side effects. CP produces two types of adverse effects on bone marrowderived cells: a dose-related reversible suppression of erythropoiesis due to the inhibition of mitochondrial protein synthesis (la); and a rare dose-independent idiosyncratic response resulting in aplastic anemia. The mechanism inducing this latter adverse effect is still unknown. Yunis (19) provided data on inherited susceptibility of DNA synthesis to CP or one of its metabolites. Several researchers, such as Weisburger et al.(17) and more recently Corbett and Chipko (3), have suggested that CP-induced aplastic anemia may be due to CP reduction metabolites. In humans and rats, reduction of the nitro moiety of CP in vivo produces arylamine or acetylated arylamine. Although potentially toxic intermediate reduction products have not yet been isolated or identified, they are assumed to be metabolites and have been synthesized and tested for toxicity by Pazdernik and Corbett (11) and more recently by Yunis et al. (20). The latter authors emphasized the -role of the p-NO2 group as the determining structural feature in the pathogenic mechanism of aplastic anemia induced by CP. They clearly showed the high toxicity of the synthetic hydroxylamine and nitroso derivatives. These are much more potent inhibitors of DNA synthesis than CP and cause irreversible stem cell damages.Since the first experiments of Glazko et al. (7), it was evidenced that the nitroreductase activities of some isolated microorganisms (14), as well as of the whole gastrointestinal microflora, may reduce the CP molecule. Goldman (8) and Scheline (13), ...