Chronic Toxicity Of Ammonia Research Articles

Dietary treatment of hyperlysinaemia.

We describe the lysine restricted, dietary management of three out of four siblings who were identified as having hyperlysinaemia. The diets, started in the neonatal period, were maintained for varying periods with unpredictable success. The propositus, who was not treated, was diagnosed at the age of 5 years, by which time he was already severely handicapped, presumably because of his metabolic disorder. Tentative recommendations are put forward for the management of this seemingly rare disorder. Mild chronic ammonia toxicity may be a factor in the pathogenesis of this condition.

Ammonia toxicity and alkalosis in sheep infested by Lucilia cuprina larvae

Guerrini V. H. 1988. Ammonia toxicity and alkalosis in sheep infested by Lucilia cuprina larvae. International Journal for Parasitology 18: 79–81. Physiological, biochemical and pathological changes in 12 sheep infested with Lucilia cuprina larvae were consistent with chronic ammonia toxicity compounded by alkalosis. Jugular ionized ammonia and calculated non-ionized ammonia concentration and jugular blood pH increased significantly in all sheep during infestation. Base excess increased significantly in six sheep which died. Consistently, sheep died within 12 h after venous blood ammonia concentration exceeded 200 μmol/l. The six sheep with ammonia concentration less than 200 μmol/l did not die. Spongy degeneration of the white matter tracts of the brain occurred in nine sheep and mild vacuolation of the tracts in three sheep confirming ammonia toxicosis.

Site‐specific acute and chronic toxicity of ammonia to Daphnia magna straus

The acute and chronic toxicity of ammonia (expressed as un-ionized ammonia nitrogen, NH3 -N) to Daphnia magna was determined in support of the development of site-specific water quality standards for ammonia in the Tittabawassee River at Midland, Michigan. The 48-h LC50 value (95% confidence interval) obtained was 2.94 (2.70 to 3.22) mg NH3 -N/L. The 21-d chronic value, presented as the maximum acceptable toxicant concentration (MATC), was between 0.42 and 0.87 mg NH3 -N/L. Expressing the chronic value as the geometric mean of 0.42 and 0.87 resulted in an MATC of 0.60 mg NH3 -N/L. The toxicity values derived during this study were similar to those reported in the literature for D. magna.

Acute and chronic toxicity of ammonia to freshwater fish: A site‐specific study

The toxicity of ammonia to the juvenile stages of the bluegill (Lepomis macrochirus) and the walleye (Stizostedion vitreum), and to the embryo, larval and juvenile stages of the fathead minnow (Pimephales promelas) was determined in support of the development of a site-specific water quality standard for ammonia in the Tittabawassee River at Midland, Michigan. There was little difference among the acute toxicities of ammonia (expressed as un-ionized ammonia nitrogen NH3 -N) to the three species tested, with 96-h LC50 values of 1.04, 1.06 and 1.50 mg NH3 -N/L for the bluegill, walleye and fathead minnow, respectively. Evaluation of the chronic data showed no concentration-related effects for hatching success and growth. However, there was a significant (α = 0.05) decrease in number of normal larvae at hatch and in larval survival at 0.26 mg NH3 -N/L and higher. The maximum acceptable toxicant concentration fell between 0.17 and 0.26 mg NH3 -N/L, or 0.21 mg NH3 -N/L when expressed as the geometric mean of these values. Both the acute and chronic values derived during this study are similar to those reported in the literature, indicating that, in this case, Tittabawassee River water quality did not influence the toxicity of ammonia to the species tested.

Chronic Toxicity of Ammonia to Fathead Minnows

Chronic effects of ammonia on the fathead minnow Pimephales promelas were studied in the laboratory in two flow-through tests, each test lasting approximately 1 year. Fish were exposed to five test concentrations over the range 0.07–0.96 mg/L un-ionized ammonia (NH3); the mean pH of the test water was 8.0, and the mean temperature was 24.2°C. The tests started with 3- to 5-d-old larvae that were reared to sexual maturity; progeny of these fish (F1 were reared until they were 60 d old. The 5% probability level was chosen to indicate significance. No effects were observed on growth or survival of parental fish at 0.44 mg/L NH3, or on egg production or viability at 0.37 mg/L, but effects on all of these were observed at 0.91 mg/L. Growth and survival of F1 larvae were not affected at 0.36 mg/L NH3, which was the highest concentration at which these were tested. Egg hatching success was not affected at 0.19 mg/L NH3, but was at 0.37 mg/L. Brain lesions were common in parental fish at all stages of development at exposure concentrations of 0.21 mg/L NH3 and higher, but not at 0.11 mg/L; no other histopathologic effects were observed at any of the test concentrations. The chronic-effects threshold concentration, based on survival, growth, and reproductive success, is estimated to be 0.27 mg/L NH3 for the conditions of these tests. Based on histological damage, however, this concentration is estimated to be 0.15 mg/L NH3.

The pathology of chronic ammonia toxicity in rainbow trout, Salmo gairdneri Richardson

Abstract. Two groups of rainbow trout fingerlings were exposed for 90 days to 0.2 and 0.4 mg/1 of un‐ionized ammonia, respectively. Several fish exposed to the higher concentration soon developed clinical signs suggestive of a neurological dysfunction but subsequently recovered. No lesion attributable to ammonia was seen in the gills of any of the fish. This raises questions about the precise role of ammonia in the production of gill diseases in intensively cultured trout.

Chronic Toxicity of Ammonia to Rainbow Trout

Abstract The chronic effects of ammonia to rainbow trout Salmo gairdneri were studied in a laboratory test conducted over a 5-year period. Fish were tested at five concentrations over the range 0.01–0.07 mg/liter un-ionized ammonia; the mean pH of the test water was 7.7, and the mean temperature was 9.3 C. Parental fish were exposed for 11 months, the first filial generation (F1) for 4 years, and the second filial generation (F2) for 5 months. The parental fish spawned of their own volition at all ammonia concentrations tested; baskets containing crushed rock served as the spawning substrate. The F1 fish did not spawn voluntarily at either 3 or 4 years of age, although manual spawning of 4-year-old F1 fish produced viable eggs. There was no significant correlation between ammonia concentration and numbers of egg lots spawned, total numbers of eggs produced, numbers of viable eggs, growth of progeny, or mortality of parents or progeny in any of the generations tested. Blood ammonia concentrations were meas...

Chronic metabolic effects of ammonia in mouse brain.

Chronic ammonia toxicity in experimental mice was induced by exposing them for 2 and 5 days to 5 % (v/v) ammonia solution. The enzymes concerned with glutamate metabolism (aspartate-, alanine- and tyrosine aminotransferases, glutamate dehydrogenase and glutamine synthetase) and (Na+ + K+)-ATPase were estimated in the three regions of brain (cerebellum, cerebral cortex and brain stem) and in liver. Glutamate, aspartate, alanine, glutamine and GABA, RNA and protein were also estimated in the three regions of brain and liver. A significant rise in the activity of (Na+ + K+)-ATPase in all the three regions of brain along with a fall in the activity of alanine aminotransferase was noticed. Changes in the activities of other enzymes were also observed. A significant increase in alanine and a decrease in glutamic acid was observed while no change was observed in the content of other amino acids belonging to the glutamate family. As a result of this, changes in the ratios of glutamate/glutamine and glutamate + aspartate/GABA was observed. The results indicated that the brain was in a state of more depression and less of excitation. Under these conditions the liver tissue was showing a profound rise in the activity of the enzymes of glutamate metabolism. The results are further discussed.

Effects of ammonia on monoamine oxidase and enzymes of GABA metabolism in mouse brain.

Acute and chronic ammonia toxicity was produced in the mice by intraperitoneal injection of ammonium chloride (200 mg/kg) and by exposure of mice to ammonia vapours (5% v/v) continuously for 2 days and 5 days respectively. The ammonia content was elevated in the cerebellum, cerebral cortex and brain stem and in liver. In acute ammonia intoxication there was a decrease in the monoamine oxidase (MAO) activity in all the three regions of brain. In chronic ammonia toxicity (2 days of exposure) a significant increase in the activity of MAO was observed in the cerebral cortex while in cerebellum and brain stem there was a significant decrease. In cerebral cortex and cerebellum there was a rise in the activity of MAO as a result of exposure to ammonia vapours for 5 days. A significant decrease was observed in the activity of glutamate decarboxylase (GAD) in all the three regions of the brain both in acute and chronic ammonia toxicity (2 days). There was a decrease in the activity of this enzyme only in the cerebral cortex in the animals exposed to ammonia for 5 days. The activity of GABA-aminotransferase (GABA-T) showed a significant rise in cerebellum and a fall in the brain stem in acute ammonia toxicity. In chronic ammonia toxicity GABA-T showed a rise in all the three regions of brain. Chronic ammonia toxicity produced a significant decrease in the content of glutamate in all the three regions without a significant change in the content of aspartate. GABA and glutamine. The content of alanine increased in all the three regions of brain under these experimental conditions. The ratio of glutamate + aspartate/GABA and glutamate/glutamine showed a decrease in all the three regions as a result of ammonia toxicity.

Mechanism of action of -N-oxalyl - l- , -diaminopropionic acid, Lathyrus sativus neurotoxin: effect on brain lysosomes.

β-N-Oxalyl-L-α,β-diaminopropionic acid (ODAP), the toxic amino-acid isolated from the seeds of Lathyrus sativus1,2, has been implicated in human neurolathyrism, a crippling disease found in central India and attributed to the consumption of this vetch3. ODAP causes convulsions in young animals when injected intraperitoneally4,5. The toxin induces hind leg paralysis in monkeys when introduced into the immediate environment of the brain through the lumbar route6. ODAP is a potent excitant amino-acid in the Betz cells of cat spinal cord7 and produces biochemical changes in the rat brain typical of an excitant amino-acid8. Chronic ammonia toxicity has been implicated in the mode of action of ODAP, leading to convulsions in young rats9. Protein degradation in the brain may be an early event in ODAP-induced convulsions10. Nucleotides have also been found to accumulate in the brain of young rats injected with ODAP (our unpublished data). Thus, a generalized increase in the catabolism of protein and nucleic acids in ODAP induced convulsions has been indicated by earlier investigations. We have examined the effect of ODAP on chick brain lysosomes possibly leading to a liberation of acid hydrolases.

The neurotoxicity of beta-N-oxalyl-L-alphabeta-diaminopropionic acid, the neurotoxin from the pulse Lathyrus sativus.

Intraperitoneal administration of beta-N-oxalyl-l-alphabeta-diaminopropionic acid, the neurotoxin from Lathyrus sativus, to 12-day-old rats causes typical convulsions within 10min. There is a striking accumulation of glutamine in the brain, and chronic ammonia toxicity is indicated. There are no changes in the amounts of urea, aspartic acid and glutamic acid in the brain. Adult rats, even when injected with a dose of excess of beta-N-oxalyl-l-alphabeta-diaminopropionic acid, do not develop symptoms, and there are no changes in the amounts of glutamine or ammonia in the brain. A significant concentration of beta-N-oxalyl-l-alphabeta-diaminopropionic acid can be detected in the brain of the young rat but not in that of the adult animal. It is concluded that beta-N-oxalyl-l-alphabeta-diaminopropionic acid interferes with the ammonia-generating or -fixing mechanisms in the brain and leads to chronic ammonia toxicity.

The 'neurotoxicity' of L-2,4-diaminobutyric acid.

The neurolathyrogen l-2,4-diaminobutyric acid is concentrated by liver, and liver damage can yield neurotoxicity; thus the neurotoxicity caused by this compound may be due to liver damage followed by secondary brain damage. 1. The intraperitoneal administration of toxic doses of l-2,4-diaminobutyric acid to rats resulted in hyperirritability, tremors and convulsions in 12-20hr. and increased the concentration of ammonia of blood and brain slightly and the concentration of glutamine of brain two- to three-fold. By contrast, toxic doses of l-homoarginine, l-lysine, l-leucine and ammonium acetate caused dyspnoea, extreme prostration, and in some cases coma in 15-30min., and increased the concentration of ammonia of blood significantly and the concentration of glutamine of brain slightly. These results indicate that l-2,4-diaminobutyric acid caused a chronic ammonia toxicity, whereas the other amino acids and ammonium acetate resulted in an acute ammonia toxicity. 2. Liver slices from l-2,4-diaminobutyric acid-treated animals and normal liver slices preincubated with l-2,4-diaminobutyric acid utilized ammonia and formed urea at a lower rate than control slices from normal rats. 3. l-2,4-Diaminobutyric acid inhibited competitively ornithine carbamoyltransferase of rat liver homogenates, thus demonstrating that this reaction is a primary site of toxicity for this neurolathyrogen. Although we were unable to show marked elevations of blood ammonia concentration after treatment with l-2,4-diaminobutyric acid, these results are interpreted to mean that ammonia utilization (urea synthesis) in liver is inhibited by l-2,4-diaminobutyric acid and that at least part of the neurotoxicity is due to a prolonged slight increase in body ammonia concentration.