摘要:

Types I and II organophosphorus compound‐induced delayed neurotoxicity (OPIDN) is characterized by axonal degeneration. Type II compounds, however, uniquely cause cell body damage. Primary cultures of bovine adrenomedullary chromaffin cells were used to investigate and assess biochemically the cell body effects of the Type II compound triphenyl phosphite (TPP). Exocytotic secretion of neurotransmitter was measured to determine whether the cytotoxic action of TPP compromised synaptic events. TPP inhibited catecholamine secretion in both a time‐ and dose‐dependent manner. By 4 h, TPP had inhibited nicotine‐induced secretion by about 85%. TPP inhibited catecholamine secretion by about 35% as early as 15 min. The IC50 for TPP was about 45 μM. TPP inhibited secretion regardless of the secretagogue used, although nicotine‐induced secretion was inhibited to the greatest extent. The Type I OPIDN diisopropyl phosphorofluoridate (DFP) and the nondelayed‐type neurotoxic organophosphorus compoundO,O‐diethyl‐O‐4‐nitrophenyl phosphate (paraoxon) did not inhibit catecholamine secretion from these cells. In contrast, when high potassium was used to induce secretion, significant stimulation was observed in the presence of DFP and paraoxon. Since Ca2+homeostasis plays a key role in both exocytosis and neuronal necrosis, its uptake into the cells was measured radiometrically in the presence of TPP or DFP. Incubation with 100 μM TPP for 4 h resulted in the inhibition of45Ca2+uptake evoked either by nicotine or K+. No significant inhibition of45Ca2+uptake was observed in the presence of DFP. TPP and DFP produced 95% and 88% inhibition, respectively, of the activity of the neurotoxic esterase enzyme (NTE), a putative target for OPIDN. Results suggest that these changes in the secretory mechanisms of the cell may be involved in the TPP‐induced pathological alterations in chromaffin cells.

ISSN:0098-4108    

DOI:10.1080/15287399309531705

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Organ retention of109Cd was studied in multiparous and virgin female mice provided tracer amounts of109Cd in drinking water and stable Cd appropriate for the itai‐itai experience in an otherwise nutrient replete solid diet. Breeder females maximally experienced 6 consecutive, 42‐d rounds of gestation/lactation. On a round‐by‐round basis, breeder organ109Cd content and concentration values were compared with those from their time‐matched virgin controls. By the end of round 5, the109Cd contents of some organs appeared to have plateaued in consecutive breeders. Comparing breeder with control values at that point, the following increases were observed: whole body (minus gastrointestinal tract), 4.7‐fold; mammary tissue, 14.1‐fold; liver, 5.9‐fold; and kidney, 3.8‐fold. For109Cd concentrations, analogous increases were mammary tissue, 15.3‐fold; liver, 4.0‐fold; and kidney, 2.4‐fold. Through the six rounds, a temporal shift in fractional109Cd distribution was noted for breeder tissues where transfer occurred from those of the mammaries, remaining carcass, and liver to the kidneys. In spite of this shift, at the end of round 6109Cd content in hepatic tissue still exceeded that in renal tissue; however,109Cd concentration was 3.3‐fold greater in the kidneys. For virgin female mice over the same period, a relatively smaller shift was observed from remaining carcass to kidneys. Unlike breeders,109Cd content was identical in hepatic and renal tissues, while109Cd concentration was 4.6‐fold greater in the kidneys. With respect to renal109Cd increases, the larger portion of these shifts had occurred by the end of round2 for virgin mice and by the end of round 6 for breeder mice. Comparison of content and concentration measures for a single, time‐matched, virgin male group with those from a virgin female group at the end of round 6 revealed distinguishable differences only for the mammary tissues; by either measure these were about threefold higher in the female one.

ISSN:0098-4108    

DOI:10.1080/15287399309531706

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Organ retention of109Cd was studied in multiparous and virgin female mice provided trace amounts of109Cd in drinking water and stable Cd as well as certain nutrient minerals, vitamins, and fat all apportioned in solid diet in amounts appropriate for the itai‐itai experience. Breeder females maximally experienced 4 non‐consecutive rounds of gestation/lactation in a total of 5 such 42‐d periods. On a round‐by‐round basis, breeder organ109Cd content and concentration values were compared with those from their time‐matched virgin controls. By the end of round 5, most organ109Cd content values in breeders were still increasing. Relative to control values at that point, the following increases were observed: whole body (minus gastrointestinal tract), 4.7‐fold; mammary tissue, 12.5‐fold; liver, 4.7‐fold; and kidney, 4.8‐fold. Analogous increases in109Cd concentration values were mammary tissue, 9.8‐fold; liver, 2.8‐fold; and kidney, 2.9‐fold. Through the five rounds, a temporal shift in fractional Cd distribution was noted for breeder tissues where transfer occurred from those of the mammaries and remaining carcass to kidneys. Although by the end of the period109Cd content in the liver still exceeded that in the kidneys,109Cd concentration was 4.7‐fold greater in renal tissues—an increase not matched by other breeder females consuming nutrient‐replete rather than nutrient‐deficient (itai‐itai) diet. For virgin female mice over the same period, a shift of similar magnitude was observed from remaining carcass to kidneys. Not unlike the breeders, hepatic109Cd content again exceeded that in renal tissues, while109Cd concentration was 4.5‐fold greater in the kidneys. With respect to renal109Cd increases, the greater portion of these shifts had occurred by the end of round 3 for both breeder and virgin mice. Comparison of both content and concentration measures for a single, time‐matched, virgin male group with those from a virgin female one at the end of round 3 showed only those for mammary tissues to be distinguishable, and by either measure were about fourfold higher in the female group.

ISSN:0098-4108    

DOI:10.1080/15287399309531707

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Organ retention of109Cd was studied in multiparous female mice 6 wk after ovariectomy or sham‐control surgery. Females previously had experienced from three to five rounds of gestation/lactation during a maximum of 5 successive, 42‐d reproductive periods. Throughout the experiment, mice were provided with tracer amounts of109Cd in drinking water as well as stable Cd appropriate for the itai‐itai experience in solid diets otherwise sufficient or deficient in nutrient quality. For sufficient‐diet females, organ109Cd content and concentration values were somewhat lower in the ovariectomized group compared to the sham control group. For deficient‐diet females, the opposite trend occurred. When ovariectomized groups were compared with round 5 breeder groups of the same dietary experience, in almost all instances organ109Cd content and concentration values were lower in the ovariectomized animals. Exceptions to this trend occurred in hepatic and especially renal tissues, where109Cd concentrations were higher in the deficient‐diet, ovariectomized group. Finally, when the deficient‐diet, ovariectomized group was compared with its sufficient‐diet counterpart, significantly higher109Cd content values were found for liver, kidneys, and whole body (minus CI tract) in the former group. Conversely, when the same tissue content values were compared between the sham‐control groups, differences without exception proved to be nonsignificant.

ISSN:0098-4108    

DOI:10.1080/15287399309531708

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

The importance of cytosolic free calcium level ([Ca2+]i) in lymphocyte activation prompted us to investigate changes in [Ca2+]i in T cells caused by mercury compounds, which have been shown to have immunomodulatory and immunotoxic properties. Using fura‐2 as fluorescent Ca2+indicator, we found that both methyl‐mercury (MeHg; 0.02–2 μM) and inorganic mercury (HgCI2; 0.01–1 μM) increased [Ca2+]i in lymphocytes from rat spleen in a concentration‐dependent manner. The effect of MeHg was rapid and the increase of Ca2+level was sustained in time, while HgCI2caused a slow rise in [Ca2+]i. The effects of mercury compounds did not appear to be associated with alterations of membrane integrity, since there was no significant difference in the extent of MnCI2quench between control and mercury‐treated cells. However, HgCI2(1 μM) and MeHg (2 μM) appeared to cause membrane damage at longer incubation times (15 min). When cells were incubated in Ca2+‐free medium (in the presence of 1 mM EDTA) MeHg still increased [Ca2+]i, though to a lesser extent, while HgCI2had no effect. Heparin, an inhibitor of inositol 1,4,5,‐trisphosphate‐induced Ca2+mobilization partially blocked this rise of [Ca2+]i, while carbonyl cyanide m‐chlorophenylhydraxone (CCCP), an inhibitor of mitochondrial function, had a lesser effect. When added together, heparin and CCCP almost completely block the response to MeHg. These results suggest that MeHg and HgCI2exert their effects of [Ca2+]i in different ways: MeHg‐induced increases in [Ca2+]i are due to influx from outside the cells as well as to mobilization from intracellular stores, possibly the endoplasmic reticulum, and, to a minor extent, the mitochondria; on the other hand, HgCI2causes only Ca2+influx from the extracellular medium.

ISSN:0098-4108    

DOI:10.1080/15287399309531709

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Selenium prevents the toxicity of the carcinogenic metal cadmium through undefined mechanisms. In this study, we determined the effects of selenium on cadmium toxicokinetics and on the ability of cadmium to induce metallothionein, a metal‐binding protein that is thought to confer tolerance to cadmium toxicity. To assess the acute protective effects of selenium, male Wistar (WF/NCr) rats were given selenium (as SeO2; 10 μmol/kg, sc) at ‐ 24, 0, and + 24 h relative to cadmium (as CdCl245 μmol/kg, sc). Over a 14‐d period this dose of cadmium killed 6 out of 10 rats, while 100% of the cadmium‐treated rats given concurrent selenium treatments survived. The acute increases in testicular weight that were seen with cadmium, indicative of edematous damage, were also prevented by concurrent selenium treatments. Further studies assessed the distribution and excretion of cadmium and its ability to induce metallothionein in rats given 40 μmol Cd/kg, sc, at time 0 and selenium (10 μmol/kg, sc) at ‐24 and 0 h. Selenium treatments enhanced cadmium accumulation at 24 h in the liver (23%), testes (145%), and epididymis (35%) but reduced renal accumulation by more than half. Urine samples, collected at 0–3, 3–6, and 6–24 h following cadmium administration, indicated a markedly reduced excretion of cadmium in selenium treated rats during all time periods. The synthesis of metallothionein was stimulated to a much lesser extent by cadmium in selenium‐treated rat kidney (41% decrease) but was unaffected in liver. The levels of cadmium‐binding proteins within the testes were markedly reduced by cadmium treatment, an effect unmodified by selenium treatments. These results suggest selenium prevents acute cadmium toxicity through a mechanism that does not involve induction of metallothionein and in spite of a markedly enhanced retention of cadmium.

ISSN:0098-4108    

DOI:10.1080/15287399309531710

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Mycotoxins are chemical compounds, produced by a variety of fungi, that can cause illness in humans and animals. This paper is a review of literature on mycotoxins with emphasis on mycotoxins in indoor air. Consideration is given to specific mycotoxins identified in indoor air, indoor sources of the mycotoxins, factors affecting mycotoxin production, potential health effects indicated by animal laboratory studies, and case studies of possible human inhalation health effects of these mycotoxins. Historically, mycotoxicoses have been associated with consumption of moldy grain. In recent years, some attention has been given to mycotoxins in dust from agricultural environments, but relatively few studies have examined mycotoxins or mycotoxin‐producing molds in indoor environments. The few indoor studies suggest that mycotoxicoses may occur in some indoor environments. More studies are needed to understand the potential for mycotoxin occurrence and significance in indoor environments.

ISSN:0098-4108    

DOI:10.1080/15287399309531711

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Synergists have been used commercially for about 50 years and have contributed significantly to improve the efficacy of insecticides, particularly when problems of resistance have arisen. In the current article we review the nature, mode of action, role in resistance management, natural occurrence, and significance in research of insecticide synergists. These natural or synthetic chemicals, which increase the lethality and effectiveness of currently available insecticides, are by themselves considered nontoxic. The mode of action of the majority of synergists is to block the metabolic systems that would otherwise break down insecticide molecules. They interfere with the detoxication of insecticides through their action on poly‐substrate monooxygenases (PSMOs) and other enzyme systems.

ISSN:0098-4108    

DOI:10.1080/15287399309531712

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399309531704

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor