PubMed Health⌕ Search

Biomedical subjects

I Nafstad

Publications and source records attributed to I Nafstad.

At least 37 records · Page 2Linked to original sources
PubMed1987

Time development of distribution and toxicity following single toxic APAP doses in male BOM:NMRI mice.

The time development of the biodistribution and the hepatotoxicity following peroral administration of 14C-acetaminophen (APAP 400 or 800 mg.kg-1; 1 microCi) was characterized in a trial procedure using male Bom:NMRI mice. APAP (400 mg.kg-1) caused a transitory hepatic glutathione (GSH) depletion while APAP 800 mg.kg-1 maximally depleted hepatic GSH throughout the 12 h trial period. A lag time between the initial GSH depletion and the ensuing hepatic necrosis was seen. From 8 h post dosing a decrease of 14C-APAP or its metabolites coincided with recovery of the hepatic GHS level and the regeneration of the hepatic cells caused by APAP 400 mg.kg-1. Hepatic glycogen depletion preceded centrilobular necrosis, and irrespective of APAP dose definite kidney damage was absent. Irrespective of APAP dose the biodistribution of 14C-APAP or its metabolites was predominantly in organs associated with metabolism and excretion. After APAP (800 mg.kg-1) significant amounts of 14C-APAP or its metabolites were present up to 24 h post dosing. The operative status of the hepatic GSH conjugative system has an important influence on the rate of elimination of toxic APAP doses. Hepatic cell necrosis with a possible effect on the circulation may play an important secondary role in the elimination of toxic APAP doses. Factors which may influence the status of the hepatic GSH conjugative system and toxicokinetics of perorally administered APAP doses are discussed.

Acetaminophen↗
PubMed1987

Effects of methylcellulose on hepatic glutathione levels and plasma ALAT following single oral administration to male Bom:NMRI mice.

1. A single p.o. dose of 1% w/v methylcellulose 0.013 ml/kg was given to male Bom:NMRI mice using untreated animals as controls. 2. A circadian fluctuation was seen in the hepatic glutathione levels (GSH) of both the methylcellulose and untreated animal group. 3. The methylcellulose administration did not affect the hepatic GSH or plasma ALAT level compared to untreated animals. 4. Histological examination did not reveal any abnormalities of the stomach wall, liver or kidney during the 12 hr trial period. 5. Male Bom:NMRI mice treated with 1% w/v methylcellulose can be considered representative of untreated controls in short-term experiments studying liver GSH and plasma ALAT levels.

Alanine Transaminase↗
PubMed1986

Efficacy of paracetamol-esterified methionine versus cysteine or methionine on paracetamol-induced hepatic GSH depletion and plasma ALAT level in mice.

The effect of paracetamol-N-acetyl-DL-methionate (PAM) in preventing paracetamol-induced hepatic glutathione (GSH) depletion and hepatic cell damage assessed by plasma ALAT level, was compared to those of concomitantly administered paracetamol and N-acetyl-L-cysteine (NAC) or N-acetyl-DL-methionine (NAM) and paracetamol 400 mg/kg (P) alone. PAM, NAM and NAC reduced hepatic GSH depletion compared to P. The concomitant administration of GSH precursors in either form apparently maintained hepatic cell integrity as evaluated by plasma ALAT compared to predose and 16 hr control measurements. No statistically significant difference between PAM, NAM and NAC was observed. In group P a statistically significant, but transitory, rise in plasma ALAT level following dosage was seen. NAC was more effective than PAM and NAM in the prevention of GSH depletion 1 hr after dosing but was less effective in promoting de novo GSH synthesis towards 16 hr. There was no statistically significant difference between PAM and NAM with respect to effect on GSH depletion or hepatic cell integrity. PAM and NAM increased the GSH level significantly above control level 16 hr after dosing. PAM is rapidly cleaved to paracetamol and methionine following dosage as shown by the observed plasma paracetamol level. PAM compares favourably in hepatoprophylactic effect, to concomitant administration of equimolar doses of free N-acetyl-DL-methionine added to the paracetamol formulation.

Acetaminophen↗
PubMed1986

Distribution and placental transfer of trichlorfon in guinea pigs.

Radiolabelled trichlorfon, dimethyl-(2,2,2-trichloro-1-hydroxyethyl)phosphonate, was administered by stomach tube to pregnant guinea pigs on days 37 and 52 of gestation and examined by the whole body autoradiography method. The results showed that the radiolabelled compound was rapidly distributed to the main organs of the dam with the highest concentrations in the liver, the kidney and the lung. No substantial concentration of radioactivity occurred in the fetuses until 30 min after administration. The uptake in the fetuses was more pronounced at the later gestational stage when the concentration in the fetal liver equalled that of the placenta.

Animals↗
PubMed1986

Prenatal effects of trichlorfon on the guinea pig brain.

The organophosphorus compound trichlorfon, dimethyl (2,2,2-trichloro-1-hydroxyethyl) phosphonate, was administered by stomach tube (100 mg/kg) to pregnant guinea pigs at two different stages of gestation (days 36, 37, 38 and 51, 52, 53). The pups developed locomotory disturbances, and post mortem examination revealed significantly decreased weights of the total brain and the cerebellum, as compared to controls. There was also a significant weight reduction particularly of the medulla oblongata, but also of the hippocampus, the thalamus, and the colliculi. Histological examination of the cerebellum revealed reduction of the external granular layer and the molecular layer, and regional absence of Purkinje cells. The activities of the neurotransmitter enzymes choline acetyltransferase (ChAT), and glutamate decarboxylase (GAD) in cerebellum were reduced as compared to the control values.

Animals↗
PubMed1986

Metabolism of hexachlorobenzene (HCB) in the isolated perfused rat liver.

The metabolism of HCB in the isolated perfused rat liver was studied by administration of [14C]HCB diluted with unlabelled HCB at a total dose of 0.1 mg HCB/ml perfusate. Metabolites in bile, perfusate and liver were studied by GLC-mass spectrometry. Histological examination of the livers showed that no hepatic necrosis had developed, although there was a slight increase in ASAT and ALAT in the perfusate and about 50% decrease in hepatic glutathione. About 0.15% of administered radioactivity was recovered in the bile within 2 hr. In the bile, HCB together with the metabolites pentachlorothiophenol and pentachlorophenol, were identified and accounted for about 20% of the radioactivity excreted. In addition, eleven metabolites with 4 or 5 chlorines were isolated. In the perfusate and in the liver, unchanged HCB was responsible for most of the radioactivity. Traces of pentachlorothiophenol and pentachlorophenol were identified in the perfusate and the liver, respectively.

Animals↗
PubMed1986

Effects of N-acetyl-DL-methionine on the liver, GSH synthesis and plasma ALAT level in male Bom:NMRI mice.

A single high peroral dose of N-acetyl-DL-methionine (859.5 mg/kg) was administered to Bom:NMRI male mice using methylcellulose as a drug vehicle. The administration of a single high peroral dose of N-acetyl-DL-methionine (859.5 mg/kg) to Bom:NMRI male mice caused an inhibition of the hepatic glutathione decrease compared to a control group treated with methylcellulose only. N-acetyl-DL-methionine caused a reduction and time delay of the hepatic glutathione decrease found in the group treated with methylcellulose only. There was no observed cellular damage of the liver or kidneys assessed histologically or by plasma ALAT after dosing with a racemic mixture of N-acetyl-DL-methionine.

Alanine Transaminase↗
PubMed1986

Organochlorine pesticides in human milk from different areas of Kenya 1983-1985.

Residue levels of the chlorinated hydrocarbons p,p'-DDT (2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane), p,p'-DDE (2,2-bis(p-chlorophenyl)-1,1-dichloroethane), hexachlorobenzene (HCB), alpha-, beta-, and gamma-hexachlorocyclohexane (HCH), aldrin, dieldrin, and polychlorinated biphenyls (PCBs) were determined in human milk of Kenyan mothers living in different areas of Kenya. The main organochlorine contaminants found in all the milk samples analyzed were p,p'-DDT and p,p'-DDE. Great regional differences were found, and mean levels of sum DDT and DDT/DDE ratio ranged from 1.1 to 18.7 mg/kg milk fat and from 0.7 to 5.7, respectively. In general, relatively low residue levels of HCB, alpha-HCH, beta-HCH, aldrin, and dieldrin were detected in 59, 37, 27, 37, and 19%, respectively, of all the milk samples analyzed. Quantifiable residue levels of PCBs and alpha-HCH were not found. The results were examined in relation to differences in living conditions with regard to agricultural activities, dietary habits, and reported use of pesticides in the various sampling areas.

DDT↗
PubMed1984

Distribution and transplacental transfer of paraquat in rats and guinea-pigs.

Radiolabelled paraquat (bis-N-(14C)methyl-4,4'-bipyridylium chloride) was administered intravenously to pregnant rats and guinea-pigs and examined by the whole body autoradiography method. Male rats were examined for comparison with the same method. The results showed that the radiolabelled compound was rapidly distributed throughout the tissues, with the highest concentrations in the cartilage, kidney, lung, spleen, salivary gland and skin. High concentrations were found in the placenta and throughout the fetuses 0.5 hr after the administration.

Animals↗
PubMed1984

Biochemical characteristics of rat superoxide dismutase and the effect caused by paraquat injection on the enzyme activity in various tissues.

Rat superoxide dismutase (SOD) prepared from the rat was not found by sedimentation in sucrose gradients or isoelectric focusing to consist of more than one molecular form. On polyacrylamide gels, however, one major and one minor activity form could be demonstrated. The sedimentation constant and corresponding molecular weight of the enzyme determined by sucrose gradient centrifugation were found to be 3.0 +/- 0.36 (34,300 +/- 4023) and the isoelectric point 4.75. These characteristics were not found to differ for SOD prepared from different rat tissues and were not affected by a single dose of 40 mg/kg paraquat given subcutaneously 48 hr prior to sacrifice. The protein contents of various tissues based on both wet and dry weight were not found to deviate from normal during 5 days following a single exposure of paraquat up to 40 mg/kg. Experiments based on SOD activity measurements in different tissues as a function of time following single exposures of paraquat, revealed the presence of a very high induction capability of the SOD protein in the rat. The results have been correlated to autoradiographic studies. A correlation between SOD induction and tissues showing high paraquat retention could be demonstrated. This was especially expressed for the lung. Due to difference in the induction pattern following exposure to 5 and 10 mg/kg paraquat, respectively, it has been suggested that the ability of the rat to bear paraquat loads might be related to the SOD induction capability in various tissues.

Animals↗
PubMed1984

Acute toxicity studies with quinuronium sulfate in laboratory animals and sheep.

The acute toxicity of quinuronium was investigated by measurements of lethal doses (LD50) in mice and rats, cholinesterase activity in vivo in whole blood, and protection from anticholinesterase activity by atropinisation in sheep and rabbits. The LD50s in mice injected i.p. and s.c. were 4.80 and 5.40 mg/kg and in rats 6.3 and 6.5 mg/kg for i.p. and s.c. routes, respectively. Signs of salivation, defecation, anorexia and muscular spasms were observed in sheep. In rabbits anorexia and depression only were observed. There was species variation in normal cholinesterase activity, rabbits being low in activity. Quinuronium inhibited cholinesterase activity from 10 min to 24 h after treatment in sheep by 24% of the normal baseline values. The enzyme activity returned to normal at 48 h. Atropinisation partially protected against anticholinesterase activity in sheep; cholinesterase activity was inhibited by only 14% of the normal baseline values 10 min to 2 h after treatment. This study indicates that quinuronium is highly toxic and that rabbits are moderately resistant.

Animals↗
PubMed1984

The influence of prazosin and propranolol on serum lipids and atherosclerosis in standard fed pigs.

The influence of prazosin and propranolol on serum lipids and atherosclerosis was evaluated in standard fed pigs during a nine months experimental period. The incidence and severity of atherosclerotic lesions was very low, and no difference could be observed neither between the two drugs nor between the drug groups and the placebo group. Prazosin and propranolol induced no marked change in the serum lipid profile. The results could be explained by the very low fat content, 3.6 per cent, in the present standard diet.

Animals↗
PubMed1984

Effects of oral lynestrenol administration on prenatal and postnatal progeny development in rabbits.

Pregnant Belted Dutch rabbits were administered lynestrenol (17-alpha-ethynyl-oestr-4-en-17-beta-ol) orally on days 6-18 of gestation at a dose of 0.5 mg/kg/day. The dose littered on term and the surviving offspring were observed until four weeks old. Neurological disturbances characterized by behavioural abnormalities and locomotor disabilities were observed. About 40% of the offspring died within four weeks, and more than 70% of these had congenital malformations.

Abnormalities, Drug-Induced↗
PubMed1983

Teratogenicity and embryotoxicity of orally administered lynestrenol in rabbits.

Pregnant Belted Dutch rabbits were administered lynestrenol 17-alpha-ethynyl-oestr-4-en-17-beta-ol) orally on days 6-18 of gestation at doses of 0.1, 0.5, and 2.5 mg/kg/day. On day 29 of gestation the does were killed and autopsied and the fetuses were examined for external, visceral and skeletal abnormalities. Lynestrenol administration produced a statistically significant increase in the number of post-implantation loss (p = 0.05) and in the average per cent of abnormal fetuses per dose group (63%, 66%, and 87% for the medicated group, versus 12% for the placebo group, p = 0.05). None of the doses tested was lethal to the does, but the average weight gain was decreased for the medium and the high dose groups. Abnormalities of the central nervous system and skeletal variants were the most frequent findings in the fetuses.

Animals↗
PubMed1983

Distribution and elimination of 14C-hexachlorobenzene after single oral exposure in the male rat.

The distribution and excretion of 14C-hexachlorobenzene (14C-HCB) after administration to rats of a single oral dose of 50 microCi 14C-HCB per kg body weight was studied by whole-body autoradiography and liquid scintillation counting. Radiolabelled HCB was distributed throughout the body in 2 hours. Peak levels were found at 4 hours in the liver and the brown fat and at 24 hours in the abdominal and subcutaneous fat. The highest concentrations were found in the adipose tissues, the bone marrow, the skin, the Harderian gland, the nasal mucosa, the praeputial gland, and the intestinal tract. After 90 days, substantial amounts were present only in the adipose tissue, the skin, the nasal mucosa, and the praeputial gland. Part of the radioactivity in the brown fat, the bone marrow, the praeputial gland, the adrenal gland, the liver, the blood, the kidney, the spleen, the lungs, the heart and the gastrointestinal contents was found not to be evaporable on sections heated to 50 degrees for 24 hrs and was considered to represent metabolites of HCB. Some radioactivity remained in the liver, the kidney, the heart and the intestinal contents after evaporation and extraction of the sections with polar and nonpolar solvents and was supposed to reflect metabolites of HCB associated to tissue macromolecules. Besides urine and faeces, the results indicated the following excretory pathways: Intestinal mucosa, sebacous glands, nasal mucosa and the praeputial and Harderian gland.

Animals↗
PubMed1983

Effects of quinuronium sulfate pre-exposure on hepatic excretion of sulfobromophthalein (BSP) as measured by isolated perfused rat liver.

Effects of quinuronium sulphate pre-exposure on hepatic excretion of sulfobromophthalein (BSP) as measured by isolated perfused rat liver was investigated. Seventeen rats were used in the study. Rats were divided into controls (Group 1, n = 5), low quinuronium treated animals (Group 2, n = 6), and high quinuronium treated animals (Group 3, n = 6) receiving 0, 1.5 or 2.3 mg quinuronium sulphate/kg intraperitoneally, respectively. Each animal was dosed 30 min. before sacrifice. After 30 min. of equilibrium perfusion, BSP was introduced and the experiment continued for 2 hours. Perfusate and bile were collected at designated time intervals and the volume of bile was noted. BSP in perfusate and bile was assayed. Half-life in minutes (t 1/2 +/- S.E.) of BSP disappearance from perfusate in groups 1, 2 and 3 were 12.5 +/- 1.8, 13.7 +/- 1.0 and 16.8 +/- 3.3, respectively. Group 2 and 3 rats had a significant decrease of BSP excretion in bile (P less than 0.01) compared to group 1 rats. Bile volumes decreased in both quinuronium pre-exposed groups of rats compared to control rats. These observations indicate that quinuronium affects liver function.

Animals↗