Biomedical subjects

M Charbonneau

Publications and source records attributed to M Charbonneau.

At least 37 records · Page 2Linked to original sources

PubMed1996

Comparison of the effect of inhaled nitric oxide and intravenous nitroglycerine on hypoxia-induced pulmonary hypertension in pigs.

Pulmonary hypertension is usually treated with intravenous (i.v.) vasodilators, but their use is limited by systemic effects. In the current study, we compared the effects of inhaled nitric oxide and intravenous nitroglycerine on pulmonary and systemic haemodynamic responses as well as on gas exchange measurements in anaesthetized pigs whose pulmonary pressure was increased by hypoxia (FiO2 = 15%). Both treatments reduced pulmonary pressure to the control level. Inhaled nitric oxide did not affect systemic arterial pressure but intravenous nitroglycerine decreased it from 126.2 to 108.8 mmHg (P = 0.04). Unlike intravenous nitroglycerine, inhaled nitric oxide increased arterial PaO2 from 5.3 to 5.9 kPa (P = 0.02). Both treatments diminished central venous pressure and left atrial pressure, suggesting a possible cardiac effect. Inhaled nitric oxide was shown to be a potent pulmonary vasodilator which attenuated pulmonary hypertension and improved arterial oxygenation without important direct effects on systemic pressure in porcine hypoxia-induced pulmonary hypertension.

Administration, Inhalation↗

PubMed1996

Combination of inhaled nitric oxide with i.v. nitroglycerin or with a prostacyclin analogue in the treatment of experimental pulmonary hypertension.

We have studied the effect of combining inhaled nitric oxide (NO) with an i.v. vasodilator agent, nitroglycerin, or ciloprost, a prostacyclin analogue, during acute pulmonary hypertension in pigs, induced by continuous infusion of a thromboxane analogue (U46619), adjusted to maintain mean pulmonary artery pressure (MPAP) at 40 mm Hg. The effects of the different treatments on MPAP and pulmonary resistances were determined. In the first part of the study, we determined the dose-response to increased NO concentrations from 5 to 40 ppm. This showed a maximum pulmonary effect with NO 5 ppm, but with no systemic effects. The effect of NO 10 ppm was then compared with two i.v. drugs. Nitroglycerin was less effective than NO on pulmonary vessels but induced significant arterial hypotension. Pulmonary vasodilatation induced by ciloprost was greater than that by NO but with the same side effects as nitroglycerin on systemic variables. We also found that the combination of NO and nitroglycerin had the same pulmonary effects as NO 10 ppm but that adding ciloprost to NO decreased pulmonary pressures significantly more than either drug used alone. We conclude that inhaled NO may be usefully combined with i.v. ciloprost but not with i.v. nitroglycerin.

Administration, Inhalation↗

PubMed1994

Mechanisms of apnea termination in obstructive sleep apnea. Role of chemoreceptor and mechanoreceptor stimuli.

Previous work from our laboratory has indicated that mechanoreceptor feedback from the respiratory muscles may play an important role in arousal and apnea termination in obstructive sleep apnea (OSA). Other studies have pointed to a prominent role for chemoreceptor stimuli. We postulated that mechanoreceptor stimuli from the respiratory system are the primary determinant of apnea termination, and that chemoreceptor stimuli exert their effect indirectly through stimulation of ventilation and thus proprioceptive feedback. To test this, we measured the diaphragmatic tension-time index (TTdi) during obstructive sleep apneas in seven male subjects with severe untreated OSA. We compared the maximal TTdi values at end-apnea during administration of air, O2, and CO2. We reasoned that if mechanoreceptor stimuli mediate apnea termination, changing the degree of chemoreceptor stimulation during apneas should not alter the level of respiratory effort at end-apnea. O2 administration produced a significant increase in end-apneic arterial oxygen saturation (SaO2) and increased apnea duration. CO2 administration led to an increase in pre- and postapneic end-tidal carbon dioxide pressure (PETCO2), and tended to shorten apneas. However, the mean value for maximal end-apneic TTdi was 0.12 +/- 0.01 (SEM) during room air breathing and was unaltered by O2 (0.12 +/- 0.01) or CO2 (0.11 +/- 0.01) administration. The consistency of end-apneic TTdi values despite the varying chemical drive supports the hypothesis that apnea termination in OSA is mediated by mechanoreceptor feedback from the respiratory system, most likely from the respiratory muscles. The influence of chemoreceptor information may be mediated indirectly through an effect on ventilatory effort.

Adult↗

PubMed1994

Changes in obstructive sleep apnea characteristics through the night.

It was our impression that the respiratory parameters in obstructive sleep apnea (OSA) worsened as the night progressed. To confirm this, we review polysomnographic studies from 66 patients with apnea-hypopnea indices (AHI) of 40 to 125 events per hour, dividing bed time into equal quartiles. As the night progressed, the mean apnea duration (MAD) increased from 27.2 s to 34.6 s (p < 0.0001), mainly from increases during NREM sleep. The proportion of time spent in apnea increased from 54 to 71% (p < 0.0001) due to increases in both MAD and the proportion of REM sleep (from 2.8 to 14.7% of the total sleep time). The AHI did not change significantly between quartiles. Even though preapneic oxygen saturation did not change and apnea duration increased as the night progressed, the end-apneic saturation did not decrease, hence the rate of oxygen desaturation decreased. Also, it was found that patients with an AHI greater than 65 events per hour increased their proportion of time spent in apnea significantly more than those with an AHI smaller than 65, as the night progressed. In the patients with an AHI greater than 85, this was due to both an increase in MAD and AHI. In conclusion, in patients with an AHI greater than 40 events per hour, the severity of apnea increased as the night progressed due to lengthening of MAD, increased proportion of REM sleep, and in the most severe patients, also an increase in AHI. Even though the exact pathophysiologic mechanisms for the observed changes are unknown, a decrease in respiratory muscle effort with consequent decrease in oxygen consumption may explain both the lengthening of the apneas and the decrease in the rate of oxygen desaturation.

Apnea↗

PubMed1994

Ultrasound-induced epileptiform activity in rats treated with hexachlorobenzene.

Hexachlorobenzene (HCB), an environmental contaminant, has caused spontaneous convulsions in infants and neonate rats born and breast-fed from exposed mothers as well as in weanling rats exposed for many weeks. This study aimed to determine if HCB causes epileptiform convulsions in adult rats. For this purpose, a controlled stimulus was used. Female Sprague-Dawley rats received HCB (100 mg/kg in corn oil) by daily gavage; on days 7 to 13, rats were exposed to a short ultrasound stimulation 24 hr after each administration. Ultrasound-induced epileptiform activity characterized by a burst of erratic running and leaping and tonic-clonic convulsions was observed in 0, 0, 10, 40, 90, 90 and 100% of rats having received a cumulative dose of 600, 700, 800, 900, 1000, 1100 and 1200 mg/kg, respectively. A similar dose-response pattern was obtained for tremors observed in HCB-treated rats. For a 800 mg/kg group left without further treatment, a three-fold increase in the percentage of rats with epileptiform activity was observed two days after the end of treatment. In summary, ultrasound stimulation has permitted us to demonstrate in a reproducible manner that adult rats treated with HCB display epileptiform activity.

Animals↗

PubMed1992

Sex-related difference in hepatic glutathione conjugation of hexachlorobenzene in the rat.

Hexachlorobenzene (HCB) induces hepatic porphyria and liver cancer in female rats, whereas toxicity is minimal in male rats. HCB is biotransformed to sulfur-containing metabolites originating from conjugation to glutathione (GSH). This study aimed to assess differences in GSH conjugation of HCB between male and female rats. Sprague-Dawley rats of both sexes were given (po, 10 ml/kg in corn oil) five consecutive doses of 100 mg/kg HCB [2 bid (7:30, 15:30) + 1 sid (7:30)]. This cumulative dose produced porphyria in female but not male rats after a delay period of 6 weeks. Animals were killed 0, 6, 12, 18, or 24 hr after the last dose. Hepatic GSH level showed a diurnal cycle in rats of both sexes, but it was more pronounced in males; the minimum level was observed at 12 hr after dosing. The GSH level in HCB-treated male rats was significantly lower than control at 6, 18, and 24 hr, whereas no significant differences were observed for HCB-treated female rats. Biliary excretion of pentachlorothiophenol, a metabolite originating from GSH conjugation of HCB, was higher in male than female rats. Liver cytosolic GSH transferase activity toward 3,4-dichloronitrobenzene was significantly higher than control level in male but not female rats given HCB. GSH transferase activity toward 1,2-epoxy-3-(p-nitrophenoxy)propane in male and female rats was not increased by HCB treatment. The liver HCB concentration at 24 hr after dosing was higher in male rats than in female rats but decreased faster thereafter. These results suggest that hepatic GSH conjugation of HCB is more important in male than in female rats. This may be related to the reduced liver porphyria observed in HCB-treated male rats compared to female rats.

Animals↗

PubMed1992

A hypothesis on p34cdc2 sequestration based on the existence of Ca(2+)-coordinated changes in H+ and MPF activities during Xenopus egg activation [corrected].

The entry into, and exit from, mitosis are controlled by a universal M-phase promoting factor (MPF) composed of at least p34cdc2 and a cyclin. Embryonic systems are convenient for studying the association and dissociation of the active MPF complex because oocytes and eggs are naturally arrested at a specific point of the cell cycle until progression to the next point is triggered by a hormonal signal or sperm. In amphibians, eggs prior to fertilization are arrested at metaphase 2 of meiosis due to the presence of a stabilized MPF complex. Fertilization (egg activation) produces a transient increase in intracellular free Ca2+, a propagating Ca2+ wave, that specifically triggers the destruction of cyclin, leading to MPF inactivation and entry into the first embryonic inter-phase. We have recently shown that intracellular pH (pHi) variations in amphibian eggs, a large increase at fertilization and small oscillations during the embryonic cell cycle, were temporally and functionally related to the corresponding changes in MPF activity. In addition, the recent finding that the pHi increase at fertilization in Xenopus eggs is a propagating, Ca(2+)-dependent pH wave which closely follows the Ca2+ wave, together with the absence in the egg plasma membrane of pHi-regulating systems responsible for that pHi increase, suggest the existence of cortical or subcortical vesicles acidifying in the wake of the Ca2+ wave, thus producing the pH wave.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Modulation of hexachlorobenzene-induced hepatic porphyria by methyl isobutyl ketone in the rat.

Potential toxic interaction between hexachlorobenzene (HCB) and methyl isobutyl ketone (MiBK) was investigated using two different schedules of toxicant administration. The first schedule involved simultaneous administration of HCB (50 mg/kg/d, p.o. in 10 ml/kg corn oil at 10.00 a.m. for 5 d/wk) and MiBK (7.5 mmol/kg/d, p.o. in 10 ml/kg corn oil at 4.00 p.m. for 3 d/wk) for 6 weeks. The second schedule involved an initial dosing of 25 or 50 mg HCB/kg/d for 12 consecutive days, followed by the administration of 7.5 mmol MiBK/kg every other day for 27 days. When administered simultaneously, MiBK reduced the severity of HCB-induced porphyria, but when given sequentially after HCB accumulation, it enhanced the porphyrinogenic response. These results suggest that the effect of combined exposure to HCB and MiBK on hepatic porphyria depends on the sequence of the administration of both chemicals, and that the mechanism involved in this interaction may invoke both the induction and inhibition of specific hepatic isoenzymes by MiBK.

Administration, Oral↗

PubMed1992

Intracellular free Ca2+ changes during physiological polyspermy in amphibian eggs.

We have made the first measurements of intracellular free calcium activity ([Ca2+]i) in urodele eggs during physiological polyspermic fertilization. Jellied eggs of the urodele amphibian Pleurodeles waltlii were impaled with intracellular Ca(2+)-selective microelectrodes and inseminated under various conditions of sperm:egg ratio to obtain various degrees of polyspermy. In 17 out of 45 cases the egg [Ca2+]i level (0.41 microM) showed no variation following fertilization. In 28 other cases, however, the egg displayed a slow increase in [Ca2+]i of 0.15 microM, starting around 15 minutes after fertilization and reaching a plateau level around 10 minutes later. The amplitude of the fertilization-associated increase in [Ca2+]i was found to be independent of the number of sperm interacting with the egg surface. Measurements with two Ca(2+)-microelectrodes impaled in single eggs showed that the increase in [Ca2+]i did not simultaneously occur at distinct places within the egg cortex and, in some cases, could be detected by only one of the two microelectrodes. This latter observation, as well as the absence of [Ca2+]i change at fertilization in some experiments, strongly suggested that each sperm interacting with the egg might, at various places, trigger a localized, non-propagating change in [Ca2+]i. Experiments in which eggs were locally inseminated, using a micropipette directed towards the site of impalement of one of the two Ca(2+)-microelectrodes, clearly established that [Ca2+]i changes, although incapable of propagating over the entire egg cortex, might nevertheless travel very slowly over short distances, their amplitude vanishing rapidly as they propagate from around the sites of sperm entry.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The increase in intracellular pH associated with Xenopus egg activation is a Ca(2+)-dependent wave.

In Xenopus eggs, the transient increase in intracellular free calcium ([Ca2+]i), or Ca2+ transient, which occurs 1-3 min after egg activation, is likely to be partly responsible for the release of the cell cycle blockade. In the present study, we have used microinjection of BAPTA or EGTA, two potent chelators of Ca2+, to buffer [Ca2+]i at various steps during Xenopus egg activation and evaluate the impact on some of the associated events. Microinjection of either one of the Ca2+ chelators into unactivated eggs prevented egg activation without, however, lowering [Ca2+]i, suggesting that only physiological [Ca2+]i changes, but not [Ca2+]i levels, were affected by the Ca2+ buffer. When BAPTA was microinjected around the time of occurrence of the Ca2+ transient, the egg activation-associated increase in intracellular pH (pHi) was clearly delayed. That delay was not due to a general slowing down of the cell cycle, since under the same conditions of microinjection of BAPTA the kinetics of MPF (a universal M-phase promoting factor) inactivation were unaffected. These results represent the first indication that the Ca2+ transient participates in determining the time of initiation of the pHi increase during Xenopus egg activation. The present results also demonstrate that the egg activation-associated pHi changes (a slight, transient decrease in pHi followed by a permanent increase in pHi) proceed as a wave propagating from the site of triggering of egg activation. Experiments of local microinjection of BAPTA support the view that the pH wave is a consequence of the Ca2+ wave, which it follows closely.

Animals↗

PubMed1991

Male rat specific nephrotoxicity resulting from subchronic administration of hexachlorobenzene.

Male rats are more sensitive to the nephrocarcinogenic effect of hexachlorobenzene (HCB) than are female rats. The purpose of this study was to shed light on this phenomenon by investigating mechanisms of subchronic nephrotoxicity of HCB. Groups of rats were administered HCB in corn oil (po) at 100 mg/kg, 5 days per week for 15 days or at 50 mg/kg, 5 days per week for 50 days. Urine was collected on Days 1, 8, and 15 for the 15-day treatment and on Day 50 for the 50-day treatment. Glucosuria, proteinuria, and enzymuria (gamma-glutamyl transpeptidase) were measured to assess renal function. Twenty-four hours after the last HCB treatment, the animals were killed and kidneys were removed for histopathological evaluation. Urine analyses showed no indication of renal dysfunction in treated animals compared to controls during the 15-day treatment. However, histology of male rat kidneys revealed degenerative and regenerative cellular foci accompanied by an increased accumulation of protein droplets in epithelial cells of the proximal tubules. The same histological observations were also made in male rats after a 50-day HCB treatment but this time they were accompanied by renal function alterations. In female rats, no such renal functional or histological alterations were observed. The histopathological observations in male rats correspond well with the protein droplet nephropathy; the latter is characteristic of the accumulation in kidney cells of alpha 2u-globulin probably caused by the reversible binding of a chemical to alpha 2u that renders the protein indigestible to kidney proteases. alpha 2u-Globulin was measured in the cytosol of male rats and was found to be increased 11-fold compared to controls. Also, HCB was found to be bound reversibly to alpha 2u. These results suggest that HCB induces a male rat specific nephropathy that could explain the higher incidence of kidney tumors in male rats compared to female rats.

Alpha-Globulins↗

PubMed1991

Thoracoscopy for the diagnosis of pleural disease.

OBJECTIVE: To assess the accuracy and safety of thoracoscopy for the evaluation of pleural disease. DESIGN: Prospective evaluation of patients referred for thoracoscopy. SETTING: University hospital specializing in chest diseases. PATIENTS: We studied 102 patients with pleural disease, the cause of which had not been determined after initial investigation, including thoracentesis and needle biopsy. Eighty-six patients had pleural effusion, 11 had pleural mass, and 5 had pleural effusion in association with a known primary lung carcinoma. INTERVENTION: All patients had thoracoscopy under local anesthesia with mild sedation. Visually directed biopsies were done of parietal pleura. MEASUREMENTS: We recorded clinical characteristics, laboratory data, findings and duration of thoracoscopy, and any complications associated with the procedure. Hospital and clinic follow-up records were reviewed, and patients were contacted by telephone 12 and 24 months after thoracoscopy to assess their health status. MAIN RESULTS: One hundred and four thoracoscopies were done in 102 patients. A definitive diagnosis was established in 95 patients: 42 had malignant pleural disease and 53 had benign pleural disease. A diagnosis of benign pleural disease using thoracoscopy could not be confirmed in the remaining 7 patients because of insufficient follow-up information. Overall, thoracoscopy was 96% accurate with a sensitivity of 91%, a specificity of 100% and a negative predictive value of 93% for the diagnosis of pleural malignancy. Thoracoscopy was well tolerated under local anesthesia and entailed hospitalization for less than 24 hours in most cases. No deaths occurred, although 1.9% of patients had major complications, and 5.5% had minor complications. CONCLUSIONS: Among patients with pleural disease remaining undiagnosed after usual initial investigation, thoracoscopy done under local anesthesia is a rapid, safe, and well-tolerated procedure with an excellent diagnostic yield that is equivalent to that of thoracotomy.

Aged↗

PubMed1991

Changes in intracellular free calcium activity in Xenopus eggs following imposed intracellular pH changes using weak acids and weak bases.

The aim of this work was to determine the potential relationships between rises in intracellular pH (pHi) and intracellular free calcium activity (Cai2+) during cell activation in Xenopus eggs. To do this, we used two weak bases, NH4Cl and procaine, and a weak acid, CO2, and measured Cai2+ variations in response to these imposed pHi variations. NH4Cl and procaine increased Cai2+ in both unactivated and activated eggs. Procaine was found to alkalinize the egg cytoplasm, whereas the other weak base, NH4Cl, acidified the egg cytoplasm. On the other hand, CO2 was found to acidify the cytoplasm and to substantially decrease Cai2+, also in unactivated and activated eggs. In addition, CO2 triggered an increase in the conductance of the plasma membrane to Cl- ions, similarly to what had been found previously with weak bases (Charbonneau, M. (1989) Cell Differ. Develop. 26, 39-52). These Cl- channels, similarly to the sperm-triggered Cl- channels during the fertilization potential, are supposed to be Ca2(+)-sensitive. Therefore, the changes in Ca2+ observed in response to CO2 do not seem to be responsible for the opening of these Cl- channels, which would rather be triggered by an increase in Cai2+ localized near the plasma membrane. We conclude therefore that weak acids and bases represent appropriate tools for studying cytosolic Ca2+ homeostasis, but not for dissecting the complex pathways involved in signal transduction.

Ammonium Chloride↗

PubMed1991

Changes in intracellular pH following egg activation and during the early cell cycle of the amphibian Pleurodeles waltlii, coincide with changes in MPF activity.

Previous work on Xenopus laevis suggests a temporal coincidence between inactivation of the M-phase promoting factor (MPF) and intracellular pH (pHi) increase during egg activation. In addition, we recently showed that during the early cell cycle of Xenopus eggs, MPF activity cycling and pHi oscillations were temporally and functionally related. In the present work, using eggs of another amphibian, Pleurodeles waltlii, which has a natural cell cycle considerably longer than that of Xenopus laevis, we show a temporal coincidence between MPF activity and pHi changes, both at the time of egg activation and at each of the following cell cycles. Egg activation-induced pHi changes in Pleurodeles did not involve classical plasma membrane ion exchangers, and were not due to the activation of a H+ conductance. On the other hand, the pHi oscillations intervening at each cell cycle were suppressed by inhibitors of protein synthesis or phosphorylation, as were their counterparts in Xenopus eggs. We propose that physiological pHi changes in Pleurodeles and Xenopus eggs might have a metabolic origin, in direct relation with the cascade of phosphorylations-dephosphorylations of proteins implicated in the control of the cell cycle.

Adenine↗

PubMed1991

Development of an experimental model for the study of hexachlorobenzene-induced hepatic porphyria in the rat.

Hexachlorobenzene (HCB) induces hepatic porphyria in rats. Various protocols of repeated cumulative and daily doses of HCB administered for several weeks until porphyria develops have been traditionally used. In order to undertake studies on early biochemical events occurring in HCB-induced porphyria, we have designed an experimental model involving the administration of a minimal amount of HCB inducing a fully developed porphyria in a well defined and predictable time frame. Groups of Sprague-Dawley rats were given (po, in 10 ml/kg of corn oil) a cumulative dose of 1,500 mg HCB/kg as 50 mg/kg for 6 weeks (5 days/week) or 100 mg/kg for 3 weeks (5 days/week). In female, but not male, rats treated for 6 weeks, HCB caused a porphyria as measured by urinary uroporphyrin and hepatic porphyrin levels; this total dose given to female rats in 3 weeks was not, however, porphyrinogenic. Female rats were given 12 consecutive daily doses of 50 mg HCB/kg followed by a no-treatment period of 30 days; this cumulative dose of 600 mg HCB/kg induced a porphyria after 6 weeks. The approximate minimally effective cumulative dose inducing porphyria was determined to be 400 mg HCB/kg, regardless of the magnitude of the daily dose (25, 50, or 100 mg/kg). Finally, the administration of a cumulative dose of 500 mg HCB/kg (50 mg/kg, 5 days/week for 2 weeks or 100 mg/kg/day for 5 days) induced after 5 to 6 weeks a porphyria that persisted for more than 500 to 600 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Inhalation versus oral administration of acetone: effect of the vehicle on the potentiation of CCl4-induced liver injury.

Acetone potentiation of liver injury is greater when corn oil is given with acetone 18 h prior to a challenge with CCl4. This study aimed to further characterize the effects of the vehicle used to administer acetone on the severity of acetone-potentiated CCl4-induced liver injury. The more severe acetone-potentiated liver injury observed when corn oil was the vehicle does not seem to be due to greater liver acetone concentrations. When corn oil was used as the vehicle to administer acetone, liver and blood CCl4 concentrations were not significantly different from those where water was the vehicle. Therefore the relationship between blood or liver acetone concentration and plasma ALT activity for orally-administered acetone was modified by corn oil. Liver triglyceride concentration measured 18 h after a gavage of corn oil was significantly higher than that for the water-treated group. A direct effect of corn oil on liver, in particular a promotion of the propagation phase in the lipid peroxidation process induced by CCl4, is proposed to explain the increase in acetone-potentiated CCl4-induced liver injury.

Acetone↗

PubMed1991

Intracellular free calcium oscillates during cell division of Xenopus embryos.

In Xenopus embryos, previous results failed to detect changes in the activity of free calcium ions (Ca2+i) during cell division using Ca2(+)-selective microelectrodes, while experiments with aequorin yielded uncertain results complicated by the variation during cell division of the aequorin concentration to cell volume ratio. We now report, using Ca2(+)-selective microelectrodes, that cell division in Xenopus embryos is accompanied by periodic oscillations of the Ca2+i level, which occur with a periodicity of 30 min, equal to that of the cell cycle. These Ca2+i oscillations were detected in 24 out of 35 experiments, and had a mean amplitude of 70 nM, around a basal Ca2+i level of 0.40 microM. Ca2+i oscillations did not take place in the absence of cell division, either in artificially activated eggs or in cleavage-blocked embryos. Therefore, Ca2+i oscillations do not represent, unlike intracellular pH oscillations (Grandin, N., and M. Charbonneau. J. Cell Biol. 111:523-532. 1990), a component of the basic cell cycle ("cytoplasmic clock" or "master oscillator"), but appear to be more likely related to some events of mitosis.

Animals↗

PubMed1991

Influence of acetone on the severity of the liver injury induced by haloalkane mixtures.

Acetone potentiation of haloalkane-induced liver injury is a well-known phenomenon. Acetone-treated rats challenged with a trichloroethylene-CCl4 mixture exhibit a more sever liver injury than that predicted by the addition of the single potentiating effects of each. The purpose of the present study was to determine if acetone exerted similar interactions with other haloalkane mixtures. The testing protocol used was designed and performed to allow categorization of interactions occurring among two or three agents. Rats were treated (p.o.) with corn oil or acetone (10.2 mmol/kg) and were administered (i.p.) 18 h later 1,1-dichloroethylene (0.6 mmol/kg), trichloroethylene (5.6 mmol/kg), tetrachloroethylene (19.6 mmol/kg), 1,1,1-trichloroethane (10.0 mmol/kg), 1,1,2-trichloroethane (1.1 mmol/kg), 1,1,2,2-tetrachloroethane (1.0 mmol/kg), CHCl3 (6.2 mmol/kg), CCl4 (1.0 mmol/kg), or a mixture of two haloalkanes (all 28 combinations were tested). Liver injury was assessed 24 h later using plasma alanine aminotransferase activity and a quantitative histological evaluation. In corn oil pretreated rats, the hepatotoxic responses observed for the 28 mixtures were additive for 26 of 28 mixtures and supra-additive for 2 of 28, whereas in acetone-pretreated rats the responses observed were additive for 17 of 28, infra-additive for 10 of 28, and supra-additive for 1 of 28. Mixtures containing 1,1,1-trichloroethane or tetrachloroethylene resulted only in no change in toxicity or infra-additivity. Increased toxic responses (additivity and supra-additivity) were observed with certain binary mixtures containing CCl4, CHCl3, 1,1,2-trichloroethane, or 1,1-dichloroethylene.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetone↗