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Biomedical subjects

G Renner

Publications and source records attributed to G Renner.

At least 55 records · Page 3Linked to original sources

Absorption in rats, dogs, pigs, and humans of nicotinic acid after oral administration of phosphatidyl inositol pentanicotinate hydrochloride (PIN).

Bound nicotinic acid in feces after oral administration of phosphatidyl inositol pentanicotinate (PIN) was determined by chromatographical isolation from acid hydrolysate and UV absorbance of the eluted nicotinic acid. With all species tested, the absorption of nicotinic acid after administration of PIN was found to be incomplete, proportions from 5 to 25% of the amount of nicotinic acid administered with PIN being recovered from feces. Humans absorbed about 75% of the nicotinic acid administered with 700 mg PIN, i.e. 230 mg. It is concluded that the presence of bound nicotinic acid in feces is due to slow absorption of the PIN or slow hydrolysis of the nicotinic acid ester. Rabbit liver homogenate, human blood plasma, and human duodenal juice were found to liberate nicotinic acid from PIN.

Animals↗

Biotransformation and some effects of 2-dimethylamino-4-(N-methylanilino)-phenol in dogs.

2-Dimethylamino-4-(N-methylanilino)-phenol (MP), an active metabolite of N,N-dimethylaniline-N-oxide in the autocatalytic formation of ferrihemoglobin, reacted quickly in dogs after intravenous injection. A dose of 14C-labeled MP which oxidized 40% of the hemoglobin disappeared from the blood in 20 min. During this period of time MP transferred catalytically electrons from ferrohemoglobin to oxygen, reacted with sulfotransferases to form the sulfuric acid ester, and was covalently bound in blood and other tissues. In the urine, in addition to the sulfuric acid ester of MP (25%), methylamine, dimethylamine, and N-methylaniline were found. Their amount indicated that most of the MP not esterified with sulfuric acid had lost a nitrogen by hydrolysis of the quinonimine. The metabolites which were covalently bound in blood and other tissues disappeared slowly, traces of radioactivity being found in blood and urine 7 days after i.v. injection of MP, 15 mg/kg. The formation of methylamines as well as N-methylaniline from MP in vivo and in blood in vitro proves that the oxidation product of MP, a purple dye, is a resonance hybrid of the two structures 2-dimethylamino-N-methyl-N-phenyl-1,4-benzoquinone-4-imonium and 4-(N-methylanilino)-N,N-dimethyl-1,2-benzoquinone-2-imonium. In addition to ferrihemoglobin MP produced numerous Heinz bodies in red cells and caused hemolytic anemia. After lethal doses necroses in the kidney tubules were found.

Aniline Compounds↗

4-Acetaminophenoxyacetic acid, a new urinary metabolite of phenacetin.

It is shown that 4-acetaminophenoxyacetic acid (APOA) is an urinary metabolite of phenacetin. APOA was isolated by means of silica gel TLC in various solvent systems from the urine of rats, dogs, and humans, collected 24 h after p.o. treatment with phenacetin (rats and dogs: 200 mg/kg; humans: three single doses of 0.5 g). Expressed as a percentage of the dose, APOA was detected at levels of 1% in rats, 0.13% in dogs and 0.04% in humans. 4-Acetaminophenoxyacetic acid was identified as its methylester--synthetized in the reaction of APOA and diazomethene--by thin layer chromatography, UV absorbance, melting point, and mass spectroscopy.

Animals↗

Mechanism of the autocatalytic formation of ferrihemoglobin by N,N-dimethylaniline-N-oxide. Structure and ferrihemoglobin forming activity of the purple dye.

The structure of the leuco compound of the purple dye which is formed in mixtrues of N,N-dimethylaniline-N-oxide (DANO) and ferrihemoglobin or ferricytochrome c was elucidated. IR, NMR, mass spectroscopy, and synthesis by oxidation of mixtures of N-methylaniline and 2-dimethylaminophenol showed that the leuco compound is produced by condensation of these two compounds. But only X-ray analysis proved the structure: 2-dimethylamino-4-(N-methylanilino)-phenol. The purple dye was produced from the leuco compound by withdrawal of two electrons and may be considered as resonance hybrid of the p-quinonimine and the o-quinonimine. When DANO was incubated with ferrihemoglobin or ferricytochrome c the oxygen of DANO was used for the production of the dye by oxidation of N-methylaniline and 2-dimethylaminophenol. The amount of N,N-dimethylaniline found in the incubation mixtures corresponded with the amount of purple dye produced. In the absence of molecular oxygen from incubation mixtures of DANO with cytochrome c the purple dye was formed at the same rate as under air. In blood in vitro the purple dye catalytically transferred electrons from ferrohemoglobin to molecuar oxygen. Its ferrihemoglobin-forming activity was lower than that of 4-dimethylaminophenol but higher than that of 2-dimethylaminophenol. The chemical mechanism of the autocatalytic formation of ferrihemoglobin by DANO is described.

Aniline Compounds↗

Reactions of 4-halogeno-N,N-dimethylaniline-N-oxide with hemoglobin.

Incubation with ferrihemoglobin or ferricytochrome c transforms 4-bromo-N,N-dimethylaniline-N-oxide (BrDANO) into 4-bromo-N,N-dimethylaniline, 4-bromo-N-methylaniline, and 2-dimethylamino-5-bromo-phenol. In a secondary reaction 4-bromo-N'-(4-bromophenyl)-6-hydroxy-N,N,N-trimethyl-1,3-phenylenediamine (U) was found from 2-dimethylamino-5-bromo-phenol and 4-bromo-N-methylaniline. The products were isolated and identified, the structure of (U) was elucidated. It has been found that the formation of ferrihemoglobin by BrDANO is an autocatalytic reaction, ferrihemoglobin being the catalyst. BrDANO reacts with the catalyst resulting in the named products. 2-Dimetnylamino-5-bromo-phenol oxidizes hemoglobin in the presence of oxygen. Thereby the catalyst ferrihemoglobin increases, which in turn increases the transformation of BrDANO to ferrihemoglobin forming derivates. This cycyle explains the autocatalytic character of the production of ferrihemoglobulin by BrDANO. The primary products of the reaction between 4-fluoro-N,N-dimethylaniline-N-oxide (FDANO) or 4-chloro-N,N-dimethylaniline-N-oxide (ClDANO) with cytochrome c, 4-fluoro- and 4-chloro-N,N-dimethylaniline, 4-fluoro- and 4-chloro-N-methylaniline, 2-dimethylamino-5-fluoro-phenol, and 2-dimethylamino-5-chloro-phenol were isolated and identified. The reactions between N,N-dimethylaniline-N-oxide (DANO), BrDANO, ClDANO, FDANO, and hemoglobin from blood of various species were studied. BrDano and ClDANO accelerate the formation of ferrihemoglobin in solutions of hemoglobin from beef and dog blood much more effectively than DANO and FDANO.

Aniline Compounds↗

Metabolic studies on pentachloronitrobenzene (PCNB) in rats.

The metabolism of PCNB in rats was studied. Metabolites isolated from rat excreta and identified were: N-acetyl-S-(pentachlorophenyl)cysteine, pentachlorothiophenol, pentachlorothioanisole, 2,3,4,5-tetrachlorothiophenol, 2,3,4,5-tetrachlorothioanisole, 2,3,4,6- and/or 2,3,5,6-tetrachloro-thiophenol and -thioanisole, 1,4-bis(methylthio)tetrachlorobenzene, 1,4-dimercapto-tetrachlorobenzene and/or 4-methylthio-tetrachlorothiophenol, pentachlorophenol, pentachloroanisole, 2,3,4,5-tetrachlorophenol, 2,3,4,5-tetrachloroanisole, 2,3,4,6- and/or 2,3,5,6-tetrachloro-phenol and -anisole, pentachlorobenzene, 2,3,4,5-tetrachloronitrobenzene, pentachloroaniline and 2,3,4,5-tetrachloroaniline.

Absorption↗

Toxicities of combinations of pentachloronitrobenzene with mercuric chloride or cadmium chloride, and hexachlorobenzene with mercuric chloride administered to rats.

1. Pentachloronitrobenzene (PCNB) and HgCl2, PCNB and CdCl2, and hexachlorobenzene (HCB) and HgCl2 were investigated for their acute oral toxicity in rats, individually and as combinations in various ratios of the organochlorine pesticides to the heavy metal chlorides. 2. The toxicity of mixtures of low dosages of the pairs tested was higher than the sum of the toxicities produced by the individual doses. 3. At increased dosages of the components in the combinations PCNB-HgCl2 and PCNB-CdCl2, the combined lethality tended towards the sums of the effects of the individual doses.

Animals↗