Chemically induced methemoglobinemias in the mouse

Smith, Roger P.; Alkaitis, Algis A.; Shafer, Paul R.

doi:10.1016/0006-2952(67)90033-0

Cited by 43 publications

(15 citation statements)

References 13 publications

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“…However, this was not the case in the National Cancer Institute study (NCI 1978) despite a concentration in the feed that was twice as high (and thus approximately 6 times the dose/kg body weight). The absence of spleen carcinogenicity in mice could well be explained by the higher efficiency in metabolising aniline (which increases with increased exposure) leading only to a slight effect on methaemoglobin formation (Smith et al 1967) and no remarkable damage to the spleen. Although hematological and pathology data after repeated oral exposure are scarce or lacking the complete absence of any non-neoplastic spleen pathology in the mice of NCI study suggests that even under the very high dose conditions the sequence of events that occur in rats does not occur in mice.…”

Section: Discussionmentioning

confidence: 96%

High-dose clastogenic activity of aniline in the rat bone marrow and its relationship to the carcinogenicity in the spleen of rats

Bomhard

2003

Arch Toxicol

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To clarify the question of clastogenicity of aniline in rats two studies were performed: a bone marrow micronucleus test and a bone marrow metaphase test. In the micronucleus test aniline (as aniline hydrochloride) was administered to groups of seven male PVG rats at single oral doses of 0, 300, 400, or 500 mg/kg body weight. Bone marrow was obtained 24 and 48 h after oral treatment. Smears of bone marrow were stained with acridine orange and erythrocytes were examined for the presence of micronuclei. Animals receiving cyclophosphamide (1x7.5 mg/kg) served as positive controls. Clinical signs observed in animals dosed at 300 mg/kg and above included cyanosis, light brown coloured urine and cold to touch. Small, but statistically significant and dose-related increases in the incidence of micronulei over the vehicle control values were observed at the 24-h sampling time only. Cyclophosphamide induced a significant and comparably much higher increase in micronuclei than aniline. In the bone marrow metaphase test aniline (as aniline hydrochloride) was administered to groups of seven male PVG rats at single oral dose levels of 0, 300, 400, or 500 mg/kg body weight. Bone marrow was sampled 18 and 30 h after dosing. A group treated with cyclophosphamide (1x40 mg/kg) served as positive control. A small increase in the percentage of aberrant cells above solvent control values was recorded in one rat at 400 mg/kg and four rats at 500 mg/kg at the 18-h sampling time only. The positive control cyclophosphamide induced a much higher rate of aberrant cells in all animals. Several lines of evidences are presented against a causal relationship between the clastogenic activity in male PVG rats at 400 and 500 mg/kg and the carcinogenicity in the spleen of Fischer 344 rats starting at 30 mg/kg in males. Among these are the dose-response relationship of the tumour incidence, the close correlation between degree of spleen damage and tumour induction, the lack of carcinogenic effects in mice even at higher dose levels, or in rats at dose levels inducing only slight haematotoxicity and spleen toxicity, and the available data on the mode of action of other chemicals inducing spleen tumours.

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Section: Discussionmentioning

confidence: 96%

High-dose clastogenic activity of aniline in the rat bone marrow and its relationship to the carcinogenicity in the spleen of rats

Bomhard

2003

Arch Toxicol

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“…Despite these beneficial effects, supernormal concentrations of nitrites in living organisms cause life-threatening states [4]. Acute nitrite intoxication is manifested primarily by methemoglobin (MetHb) formation (nitrite ion in contact with RBC (red blood cells) oxidizes ferrous iron in hemoglobin to the ferric state, forming stable MetHb which is incapable of oxygen transport) and resultant hypoxia [5], and mice [6] and rats [7,8] exposed to sodium nitrite were shown to achieve elevated concentrations of MetHb in their blood. Therefore, environmental nitrite can cause physiological disturbances such as decreases in total hemoglobin, hematocrit, and RBC.…”

Section: Introductionmentioning

confidence: 99%

The protective potential of Yucca schidigera (Sarsaponin 30®) against nitrite-induced oxidative stress in rats

et al. 2009

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The present study was designed to determine the protective effects of Yucca schidigera (Ys) against oxidative damage induced by acute nitrite intoxication as well as the histopathological evaluation of Ys in rats. The rats were divided into three groups each containing 12 rats: control (C); nitrite intoxication (N); Ys + nitrite intoxication (NY). C and N groups were fed standard rat feed (SRF). The NY group was fed SRF + 100 ppm Ys powder for 4 weeks. Acute nitrite intoxication was induced by subcutaneous (s.c.) administration of sodium nitrite (60 mg/kg) 1 day after the feeding period. Fifty minutes after sodium nitrite administration, blood samples and tissues including lung, liver, and kidney were collected for clinical biochemistry and histopathological investigations. Ys treatment was found to decrease methemoglobin, blood and tissue malondialdehyde, and tissue nitric oxide concentrations, and to increase the glutathione in blood and various tissues. However, plasma nitric oxide, total antioxidant activity, beta-carotene, and vitamin A did not differ between N and NY groups. While the N group rats showed distinct pathology in various tissues (compared with controls), the NY group had similar lung and liver pathology to the control. Only moderate or mild hemorrhage and hyperemia were seen in kidneys of NY group rats. Consequently, the natural compounds found in Ys, such as polyphenols, steroidal saponins, and other phytonutrients, could be used to substantially protect the organism from nitrite-induced oxidative damage and its complications.

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“…Several studies specifically addressed the hematological effects resulting from the administration of PAPP (84,85). Although there was some species variation, the Primary hematological effects observed included the appearance of Heinz bodies and hemolytic anemia.…”

Section: Hematological Effects Of Papp In Animalsmentioning

confidence: 99%

“…The ob-served differences in the hemolytic effects of nitrite or PAPP would support this generalization (7). At present, the mechanism by which PAPP produces hemolysis is unknown (85). Other chemicals (i.e., acetanilide) are known to produce methemoglobinemia as well as hemolysis (dogs) (100), but the mechanism is not thought to be due to bone marrow suppression but is common with aminophenyl compounds.…”

Section: Hematological Effects Of Papp In Animalsmentioning

confidence: 99%