Nitrate In Rats Research Articles

Kinetic studies on nitrite and nitrate in rats by ion-pair chromatography

A highly sensitive and specific ion-pair Chromatographic method is presented for the simultaneous determination of nitrite (NO 2 −) and nitrate (NO 3 −) in plasma. The detection limits are 2 μmol No 2 −/l and 8 μmol No 3 −/l with recovery rates of 98–99%. The applicability of this method to clinical medicine is demonstrated using No 2 −-loaded rats as a biological model: following intravenous infusion or intragastric application of No 2 −, blood levels of No 2 −, No 3 − and methemoglobin are measured during 2–64 min. The kinetic data obtained reflect the complex metabolism of No 2 − and No 3 − in living organisms.

Nitrate biosynthesis in the rat. Precursor-product relationships with respect to ammonia.

The endogenous biosynthesis of nitrate in rats was investigated by using 15NH3 administered as a continuous intravenous infusion for as long as 96 h. A comparison of the enrichment of 15N in urinary nitrate after a 24 h infusion revealed that it was 36% of the enrichment of plasma NH3 and about 50% of the enrichment of plasma urea and urinary NH3. Continuous infusion of 15NH3 for 96 h showed that a plateau for the incorporation of NH3 into nitrate is reached by 24 h, whereas the enrichment of urinary NH3 and urea increase during the 96 h. After the infusion of progressively larger doses of 15NH3, the concentration of nitrate synthesized de novo increased. Although there was a significant correlation between plasma 15NH3 concentration and 15NO3- appearance, a given change in plasma NH3 concentration does not produce a direct proportional change in nitrate synthesis. Our findings indicate that NH3 is a quantitatively significant nitrogen precursor for nitrate, but that approx. 50% of nitrate nitrogen is derived from other, as yet unidentified, sources.

Neurochemical effects of ethylhexyl nitrate in rats

Rats injected i.p. with 100 mg ethylhexyl nitrate/kg body wt excreted 0.3% of the dose in the urine within 24 h. No urinary nitrite was found within 5 postinjection hours while an output of 26.9 ± 15.8 μg nitrite/h × kg body wt. was detected between 5–24 h. Cerebral glutathione concentration was below the control level after 1 day but returned to control value after 3 and 7 days postinjection. Brain acetylcholine esterase activity was marginally decreased after 1 day while RNA and succinate dehydrogenase assay excluded major structural damage. It seems that the mechanism of clinical symptoms experienced by exposed workers are comparable to those exposed to dynamite and are largely functional.

The behaviour of uranium-233 oxide and uranyl-233 nitrate in rats.

233UO2 and 233UO2(NO3)2 in aqueous suspension have been administered to rats by pulmonary intubation. The 233U associated with the fraction of the 233UO2 less than 4 nm in diameter translocates from lungs to blood at the same rapid rate as 233U from 233UO2(NO3)2. Identical reactions with blood plasma and lung fluid were observed whether the 233U was administered as less than 4 nm 233UO2 particles or 233UO2(NO3)2. It is suggested that oxidation of UO2 to UO3 occurs followed by the formation of uranyl ion. In blood plasma, approximately 50 per cent of the 233U is bound to transferrin, 25 per cent to citrate and 25 per cent on bicarbonate.

Short-term inhalation toxicity studies with peroxyacetyl nitrate in rats

The inhalation toxicity of peroxyacetyl nitrate (PAN) was examined in acute (single exposure), sub-acute (4-week repeated exposure) and subchronic (13-week repeated exposure) studies in rats. The 4-h LC 50 was found to be 95 ppm. In the 4-week study rats were exposed to 0, 0.9, 4.1 or 11.8 ppm PAN vapour for 6 h/day, 5 days/week. Exposure to 11.8 ppm caused abnormal behaviour, growth retardation, mortality, elevated haemoglobin contents, haematocrit values and erythrocyte counts, increased lung weights and severe inflammatory changes and epithelial hyper- and metaplasia in the respiratory tract. At 4.1 ppm minimal behavioral disturbance, transient growth depression, slightly increased lung weights and mild histopathological changes in the respiratory tract were found. At 0.9 ppm no treatment-related alterations were detected. In the 13-week study rats were exposed to 0, 0.2, 1.0 or 4.6 ppm PAN vapour for 6.5 h/day, 5 days.week. Exposure to 4.6 ppm resulted in changes similar to those found at 11.8 ppm in the 4-week experiment, but no mortality occurred. At 1.0 ppm minimal irritation of the mucous membranes in the nasal cavity was the only PAN-related effect observed. No treatment- related changes were seen at 0.2 ppm. It was concluded that the no-toxic- effect level is between 0.2 and 1.0 ppm, and very probably close to the upper value.

3034. Lead strikes the foetus McClain, R. M. & Becker, B. A. (1975). Teratogenicity, fetal toxicity, and placental transfer of lead nitrate in rats. Toxic. appl. Pharmac.31, 72

3034. Lead strikes the foetus McClain, R. M. & Becker, B. A. (1975). Teratogenicity, fetal toxicity, and placental transfer of lead nitrate in rats. Toxic. appl. Pharmac.31, 72

The effects of various chelating agents on the teratogenicity of lead nitrate in rats

Lead nitrate alone or lead chelated with ethylene-diaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), iminodiacetic acid (IDA), and penicillamine (PEN) was administered iv to pregnant rats on days 9, 11, or 16 of gestation (day 1 = vaginal plug) at a 1:1 molar ratio of chelating agent to lead at a dosage of 35 or 50 mg/kg with respect to lead nitrate. Lead nitrate alone caused resorptions and fetal malformations on day 9, resorptions on day 11, and resorptions and hydrocephalus following treatment on day 16. The lead-chelate complex either reduced or equaled but did not enhance the overall embryo or fetal toxicity. There were no qualitatively different effects produced with chelated lead versus lead alone. The chelating agents were more effective after treatment on gestation day 9 that after days 11 or 16. Ethylenediaminetetraacetic acid produced the greatest reduction in overall effect, with PEN and NTA intermediate, while IDA provided the least overall protective effects.

Teratogenicity, fetal toxicity, and placental transfer of lead nitrate in rats

Single doses of 25–70 mg/kg of lead nitrate were administered iv to pregnant rats on Days 8–17 of gestation (Day 1 = sperm found). Malformations were produced with lead when administered on Day 9 of gestation, producing a urorectocaudal syndrome of malformations. Lead nitrate was increasingly embryo- and fetotoxic when administered on later days of gestation (Days 10–15) but not teratogenic. Hydrocephalus and hemorrhage of the central nervous system were produced on Day 16 of gestation. On Day 16 and therafter, fetal toxicity (resorptions) sharply declined. Postnatal survival of newborn exposed in utero to lead on Day 9 of gestation was very poor. Significant quantities of lead were transferred into the fetus; however, the placenta appeared to greatly limit the passage of lead since large maternal-fetal concentration gradients existed.

Distribution of 3H-methylatropine in rat brain

The cerebral distribution of 3H-atropine sulphate and 3H-methylatropine nitrate in rats was investigated 30 min after intraperitoneal administration of both drugs. Both compounds were found to be pure (>98%) by paper chromatography and paper electrophoresis. The distribution of radioactivity over various metabolites in liver, plasma and CNS was also carried out by paper chromatography and paper electrophoresis. Radioactivity in the CNS after 3H-atropine administration is about three times higher than it is after injection of 3H-methylatropine. The penetration of radioactivity into the CNS, however, is very low. It is estimated that following the systemic administration of a dose of 10 mg/kg, 0.100 nmol atropine or 0.012 nmol methylatropine per 100 mg fresh brain tissue is present after 30 min. The distribution of atropine over eleven parts of the brain tends to be homogenous, although there are indications that atropine is taken up preferentially in cerebellum, pons and hypothalamus. Methylatropine is preferentially taken up by cerebellum, pons, preoptic and septal area. The significance of these findings for studies in which methylatropine is applied locally in the brain, is discussed. It is concluded that blockade of cholinergic receptors in the CNS is possible after peripheral administration of atropine and methylatropine as well.