Toxicology and applied pharmacology
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Toxicol. Appl. Pharmacol. · May 1990
Effects of hydrogen sulfide exposure on lung mitochondrial respiratory chain enzymes in rats.
Fischer-344 rats were exposed for 4 hr to various concentrations of hydrogen sulfide (H2S) gas and killed either immediately or at 1, 24, or 48 hr after exposure. Mitochondrial fractions from lung tissues were assayed for the activities of respiratory chain enzymes. Exposure of rats to a low concentration (10 ppm) of H2S caused no significant changes in the activities of lung mitochondrial enzymes. ⋯ The nature of sulfide inhibition of cytochrome c oxidase was noncompetitive with respect to ferrocytochrome c. Because the activities of NADH-cytochrome c reductase and succinate-cytochrome c reductase were not significantly altered by H2S exposure and in vitro treatments with low concentrations of sulfide, it is concluded that under physiological conditions H2S would block the respiratory chain primarily by inhibiting cytochrome c oxidase. Such a biochemical impairment would lead to functional (histotoxic) hypoxia in the lung tissues.
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Toxicol. Appl. Pharmacol. · Jun 1989
Effects of altered platelet number on pulmonary hypertension and platelet sequestration in monocrotaline pyrrole-treated rats.
To study the role of platelets in monocrotaline pyrrole (MCTP)-induced pulmonary hypertension, pulmonary sequestration of 111In-labeled platelets in rats treated with MCTP and anti-rat platelet serum (PAS) was examined. Lung injury from a single, intravenous injection of MCTP (3.5 mg/kg) at Day 8 was evident as elevated lung weight and lavage fluid protein and lactate dehydrogenase activity. Additionally, right ventricular hypertrophy and elevated pulmonary arterial pressures (PAP) occurred. ⋯ Apparently, platelet depletion delayed the development of the pulmonary hypertensive response. Supranormal platelet numbers produced by splenectomy did not affect MCTP-induced lung injury or the elevation in PAP. These results support the hypothesis that the development of MCTP-induced pulmonary hypertension is mediated in part by platelets.
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Toxicol. Appl. Pharmacol. · Feb 1989
Effects of subacute administration of physostigmine on blood acetylcholinesterase activity, motor performance, and soman intoxication.
Subacute administration of carbamates is under study as pretreatment against soman, a toxic anticholinesterase agent. In this study, the sustained release of physostigmine salicylate (Phy) in rats was achieved via osmotic minipumps; each pump contained 2 ml of Phy solution (0.4, 10, or 50 mg/ml) and delivered 2.5 microliter/hr for 28 days. At the corresponding dosage rates, rat whole blood acetylcholinesterase (AChE) activity was suppressed by approximately 11, 42, and 66%, respectively. ⋯ On Day 27 the rats were given 0.08 mg/kg, im, of scopolamine (SCP), 30 min before exposure to soman (58 micrograms/kg; 1 LD50, iv). In combination with SCP, the two highest levels of Phy prevented lethality and a decrement in ARR performance by soman, while the lowest level showed 40% lethality after soman and the survivors exhibited partial recovery to their own presoman control performance by 24 hr. These results suggest that, in a pretreatment mode, 42-66% inhibition of AChE by sustained exposure to Phy, with an acute dose of cholinolytic, would suffice to protect against lethality and motor performance decrement by a toxic level of soman.
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Toxicol. Appl. Pharmacol. · Apr 1987
5-Hydroxytryptamine and thromboxane in platelets from rats treated with monocrotaline pyrrole.
Monocrotaline pyrrole (MCTP), a metabolite of the plant toxin monocrotaline, produces pulmonary vascular injury, pulmonary hypertension, and right ventricular enlargement (RVE) in rats by an unknown mechanism. A role for platelets has been suggested by the observation that antibody-induced thrombocytopenia reduces the RVE caused by MCTP. The platelet can release a number of vasoconstrictive agents, such as 5-hydroxytryptamine (5HT) and thromboxane A2 (TxA2), that could possibly contribute to pulmonary hypertension. ⋯ At concentrations up to 250 micrograms/ml, MCTP added in vitro to PRP from untreated rats did not affect the concentration of TxB2 released during aggregation induced by arachidonic acid. Only at very high concentrations (1 mg/ml) did MCTP abolish the aggregation response and depress TxB2 release in PRP. These results indicate that MCTP treatment does not affect platelet 5HT content and does not affect basal TxB2 production or TxB2 release by platelets stimulated in vitro.
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Toxicol. Appl. Pharmacol. · Mar 1986
Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate.
The effects of lead ingestion on parameters indicative of copper status, and particularly on the activity of the copper-dependent metalloenzyme superoxide dismutase (SOD) in erythrocytes, were investigated in weanling and neonatal rats. In a series of experiments, Sprague-Dawley or Long-Evans rats were fed a nutritionally adequate purified diet (AIN-'76). Lead acetate was given orally in the drinking water (0, 100, 250, or 500 ppm Pb) to groups of 23 to 26-day-old rats for 5 weeks or intragastrically (0, 5, 11, 22, or 45 mg Pb/kg body wt/day) to pups from postnatal Days 2 through 20. ⋯ Despite high blood lead concentrations (1-3 micrograms/ml), SOD activity was not decreased in the neonatal rat. In addition, lead had no direct effect in vitro on the activity of bovine blood superoxide dismutase. On the basis of both the in vitro and in vivo studies, it appears likely that the observed decrease in SOD in young rats is caused indirectly by a lead-induced copper deficiency rather than by a direct inhibitory effect of lead.