美金刚对敌敌畏染毒大鼠脑组织NMDA受体的保护作用

目的　研究美金刚对敌敌畏染毒大鼠脑组织N 甲基 D 天冬氨酸 (NMDA)受体的保护作用及其治疗有机磷农药中毒的机制。方法　雄性SD大鼠用 2 5mg/kg敌敌畏染毒 ,再用美金刚 5、15、45mg/kg治疗 ,观察大鼠中毒症状出现强度与时间 ;染毒后 16h测定大鼠全血和脑组织乙酰胆碱酯酶 (AChE)活力及NMDA受体活性。结果　美金刚 15、45mg/kg治疗组大鼠中毒症状出现时间分别为 (18.40± 1.14 )、(2 1.40±1.52 )min ,较敌敌畏组 [(16.75± 1.62 )min]明显延长 ;肌颤强度分别为 1.60± 1.14、0 .80± 0 .84,较敌敌畏组(2 .85± 0 .3 7)明显减轻 ;症状总评分分别为 8.80± 1.79、9.0 0± 2 .2 4,较敌敌畏组 (14 .60± 1.70 )明显改善。美金刚对敌敌畏染毒大鼠全血和脑组织AChE活力均未见明显影响。敌敌畏染毒大鼠脑组织NMDA受体密度减少、亲和力下降 ,其Bmax和Kd值分别为 (0 .46± 0 .0 6)pmol/mgpro、(75.55± 7.87)nmol/L ,分别较阴性对照组 [(0 .62± 0 .0 4)pmol/mgpro、(3 7.3 7± 4.17)nmol/L]下降和上升。 5、15mg/kg美金刚可拮抗敌敌畏染毒对大鼠脑组织NMDA受体的影响 ,这两组的Bmax值分别为 (0 .55± 0 .0 7)、(0 .64± 0 .0 7)pmol/mgpro ,Kd值分别为 (3 8.68± 4.54)、(3 2 .58± 3 .90 )nmol/L。美金刚 45m     

敌敌畏对大鼠乙酰胆碱酯酶抑制作用的基准剂量和未观察到有害作用水平比较

目的 比较敌敌畏对大鼠乙酰胆碱酯酶抑制作用的基准剂量(BMD)和未观察到有害作用水平(NOAEL).方法 将80只健康清洁级成年雌性SD大鼠按体重随机分为8组,分别为对照(蒸馏水)组和0.22、0.44、0.88、1.75、3.50、7.00、14.00 mg/kg敌敌畏染毒组,采用灌胃方式进行染毒,染毒容量为10 ml/kg,每天1次,连续染毒21d.测定大鼠脑组织海马、皮质和血清中的乙酰胆碱酯酶活力,并计算BMD值和NOAEL值.结果 与对照组比较,7.00～14.00 mg/kg敌敌畏染毒组大鼠脑组织海马和3.50～14.00 mg/kg敌敌畏染毒组大鼠脑组织皮质及1.75～14.00 mg/kg敌敌畏染毒组大鼠血清中的乙酰胆碱酯酶活力均下降,差异有统计学意义(P＜0.05);且大鼠血清乙酰胆碱酯酶活力随敌敌畏染毒剂量的升高而下降.敌敌畏经口灌胃对大鼠脑组织皮质、海马和血清的BMD分别为1.80、0.81、0.51 mg/kg,95％可信区间下限(BMDL)分别为1.42、0.44、0.30 mg/kg; NOAEL分别为3.5、1.75、0.88 mg/kg.结论 BMD法比NOAEL法得到的安全参考剂量更为保守,能为人群提供更广泛的保护.     

乐果染毒28天对大鼠脑组织及外周血淋巴细胞M受体mRNA水平的影响

目的研究低剂量乐果预处理诱导大鼠产生耐受及再暴露于高剂量乐果时其脑组织与外周血淋巴细胞毒草碱型乙酰胆碱受体(M受体)变化情况，探索耐受产生的机制。方法大鼠分两个阶段染毒：连续28d皮下注射25mg／kg乐果后，分别再给以生理盐水及50、100mg／kg乐果激发。记录大鼠的中毒症状，测其全血乙酰胆碱酯酶(ACHE)活力。激发后24h，测大鼠脑AChE活力和M1、M2受体亚型密度和受体mRNA水平；测大鼠外周血淋巴细胞M3受体mRNA基础水平和诱导水平。结果乐果28d染毒过程中，大鼠全血AChE活力持续下降，第13天达最低，乐果激发染毒使其活力进一步下降；乐果预处理组大鼠脑组织AChE活力远低于对照组，且随激发剂量升高而下降。对照组、25mg／kg乐果预处理组和预处理后50、100mg／kg乐果激发组大鼠脑组织M1受体密度分别为979．15、856．54、539．46、539．14fmoL／mgpro，M1受体mRNA水平相对数值分别为2．59、2．47、2．20和1．81，同M1受体密度变化基本一致，但激发剂量增加，其水平继续下降；M2受体密度分别为507．38、611．11、548．42、337．47fmoL／mgpro，预处理对之影响不明显，但随激发剂量升高，其密度下降，M2受体mRNA水平则变化不明显。这4组外周血淋巴细胞M3受体mRNA基础水平差异不明显，而诱导水平随乐果激发剂量升高而下降。结论低剂量乐果可以诱导动物产生对乐果毒性的耐受，M受体密度的下降是其可能机制。M受体密度的下降可能由其mRNA水平下降引起。外周血淋巴细胞M3受体mRNA的诱导水平同脑组织M1受体mRNA水平一致。     

抗虫灵对大 鼠全血和人红细胞膜乙酰胆碱酯酶的抑制作用

目的应用Ellman法或羟胺法检测乙酰胆碱酯酶(AChE)活性.方法研究有机磷杀虫剂抗虫灵对大鼠全血和人红细胞膜AchE活性的影响.结果雄性大鼠每天经口给以抗虫灵6.81mg/kg连续5d可引起全血AChE活性明显下降;动物亚慢性90d染毒后,雄性中剂量(0.25mg/kg)和高剂量(1.00mg/kg)组动物与雌性低剂量(0.05mg/kg)和高剂量(1.00mg/kg)组动物全血AChE活性明显下降;体外试验发现,抗虫灵在所试验的5×10-8～5×10-8mol/L的浓度范围内对人红细胞膜AChE活性都有明显抑制作用,并有剂量和时间依赖性,而且这种抑制为不可逆抑制.结论抗虫灵对AChE活性的抑制是其毒作用的重要机理,符合有机磷杀虫剂毒作用的一般规律.     

一氧化氮合酶抑制剂在N-甲基-D-天(门)冬氨酸诱导的神经细胞凋亡中的作用研究

目的探讨一氧化氮合酶抑制剂(nitric oxide synthase inhibitor,NOS inhibitor)在N-甲基-D-天(门)冬氨酸(N-Methyl-D-Asparate,NMDA)诱导的兴奋性神经毒中的作用及其可能的作用机制。方法原代培养24 h内新生SD大鼠脑组织皮层神经元,利用免疫荧光方法鉴定细胞纯度。将培养的神经元随机分为对照组、NMDA染毒组和NMDA+NG-硝基-L-精氨酸甲酯(L-NAME)染毒组,每组24个平行。NMDA+L-NAME染毒组加入终浓度为100μmol/L的L-NAME染毒1 h后,在NMDA+L-NAME染毒组和NMDA染毒组分别加入终浓度为100μmol/L的NMDA染毒2 h。测定神经元细胞的活性、NO浓度、细胞凋亡情况及磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)的表达。结果免疫荧光显示90%细胞为兔抗大鼠神经元特异性烯醇化酶(neuronal specific enolase,NSE)阳性细胞;与对照组相比,NMDA染毒组与NMDA+L-NAME染毒组大鼠脑组织神经元中NO的浓度、细胞凋亡率及p-p38MAPK的表达明显升高,细胞活性明显下降,差异均有统计学意义(P<0.01);而与NMDA染毒组相比,NMDA+L-NAME染毒组大鼠脑组织神经元中NO的浓度、细胞凋亡率及p-p38MAPK的表达明显降低,细胞活性明显上升,差异有统计学意义(P<0.01)。结论 NMDA诱导的神经细胞凋亡部分依赖NO毒性作用,抑制NO的毒性作用可部分抑制神经细胞凋亡。     

Effect of Nitricoxide Synthase Inhibitor on Neurons Apoptosis Induced by NMDA

目的 探讨一氧化氮合酶抑制剂(nitric oxide synthase inhibitor,NOS inhibitor)在N-甲基-D-天(门)冬氨酸( N-Methyl-D-Asparate,NMDA)诱导的兴奋性神经毒中的作用及其可能的作用机制.方法 原代培养24h内新生SD大鼠脑组织皮层神经元,利用免疫荧光方法鉴定细胞纯度.将培养的神经元随机分为对照组、NMDA染毒组和NMDA+NG-硝基-L-精氨酸甲酯(L-NAME)染毒组,每组24个平行.NMDA+L-NAME染毒组加入终浓度为100 μmol/L的L-NAME染毒1h后,在NMDA+L-NAME染毒组和NMDA染毒组分别加入终浓度为100 μmol/L的NMDA染毒2h.测定神经元细胞的活性、NO浓度、细胞凋亡情况及磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)的表达.结果 免疫荧光显示90％细胞为兔抗大鼠神经元特异性烯醇化酶(neuronal specific enolase,NSE)阳性细胞;与对照组相比,NMDA染毒组与NMDA+L-NAME染毒组大鼠脑组织神经元中NO的浓度、细胞凋亡率及p-p38MAPK的表达明显升高,细胞活性明显下降,差异均有统计学意义(P＜0.01);而与NMDA染毒组相比,NMDA+L-NAME染毒组大鼠脑组织神经元中NO的浓度、细胞凋亡率及p-p38MAPK的表达明显降低,细胞活性明显上升,差异有统计学意义(P＜0.01).结论 NMDA诱导的神经细胞凋亡部分依赖NO毒性作用,抑制NO的毒性作用可部分抑制神经细胞凋亡.     

乐果亚急性染毒诱导大鼠耐受以及对大鼠脑组织M受体的影响

[目的]通过连续低剂量乐果染毒，建立大鼠对乐果的耐受模型，然后再用高剂量乐果激发染毒，观察激发染毒后大鼠全血胆碱酯酶和脑组织中M受体的变化，以了解耐受的生理病理意义。[方法]将大鼠随机分为对照组及3个染毒组。首先对各染毒组连续14d皮下注射25mg／kg乐果，然后将染毒动物分别给以生理盐水、50mg／kg、100mg／kg乐果激发。实验过程中系统记录动物的中毒症状，采集尾静脉血检测胆碱酯酶活性。激发24h后，处死动物，取脑组织测定胆碱酯酶活性和M受体M1、M2亚型密度、亲和力，并作电镜检查。[结果]低剂量诱导染毒后，全血胆碱酯酶活性持续下降，到第12天时接近最低值，激发染毒后，大鼠全血胆碱酯酶活性下降不明显，生理盐水激发组全血胆碱酯酶活性有一定恢复。不同剂量激发的动物脑组织中Ml、M2受体的密度和亲和力差别经检验仅M1受体密度下降有统计学意义。脑组织电镜检查发现高剂量激发组动物有典型神经元坏死。[结论]耐受动物可以抵抗更高剂量的乐果染毒而不出现明显的有机磷急性中毒症状，说明耐受动物有了保护能力。但是电镜下观察到脑神经元的典型坏死，提示时受可能存在潜在的健康危害。     

急性氯化甲基汞染毒大鼠脑某些抗氧化指标的变化

目的 对SD大鼠经腹腔注射氯化甲基汞(MeH必)的急性染毒方式，观察其对大鼠脑组织和血清某些抗氧化指标的变化。方法 用甲基汞对大鼠染毒24h后，断头处死，取血清和脑组织检测谷胱甘肽过氧化物酶(GSH—Px)和超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。结果 染毒24h后，5．00mg／kg和10．00mg／kg剂量的大鼠脑组织匀浆和血清中的GSH—Px活性和S0D活性下降，MDA含量上升。结论 甲基汞染毒24h后，GSH—Px和SOD活性下降，MDA含量上升，表明这种作用对MeHgCl引起的神经毒性有一定的敏感性。MeHgCl可使脑组织和血清中某些抗氧化指标发生变化。     

甲基汞急性暴露大鼠脑中汞蓄积及胆碱能神经递质改变的研究

目的 研究低剂量甲基汞短期暴露的神经毒性作用,为进一步探讨甲基汞早期神经毒性机制提供实验依据。方法 采用SD大鼠腹腔注射甲基汞,剂量分别为0．05、0．50及5．00mg／kg,并设对照组,分别暴露20min、1、4、24h时测定大鼠脑组织总汞含量、乙酰胆碱(ACh)含量及乙酰胆碱酯酶(AChE)活力。结果 除0．05mg／kg剂量组外,其余两组大鼠脑组织中汞含量在暴露20min就显著升高;0．05mg/kg组大鼠暴露4h后,脑汞含量也出现显著升高。各剂量组大鼠脑组织ACh及AChE都在暴露20min后就出现显著变化,并显示一定的剂量——效应和时间——效应关系。结论 甲基汞低剂量(0．05mg／kg)短时间暴露(20min)时脑组织ACh和AChE的改变表明此时可能启动了中枢神经系统某种调控机制。随暴露剂量和暴露时间增加,甲基汞蓄积于大鼠脑组织中,可引起脑组织ACh含量和AChE活力显著变化。     

乐果90 d染毒对大鼠大脑皮质GABA系统的影响

[目的]研究乐果[O,O-二甲基-S-(N-甲基氨基甲酰甲基)二硫化磷酸酯]90d染毒对大鼠大脑皮质γ-氨基丁酸(GABA)系统的影响。[方法]48只健康雄性SD大鼠分成4组,剂量分别为O(生理盐水)、5、10、20mg/kg,灌胃给药,每周染毒5d(次),实验周期90d,每天称重1次,每3天记录动物饲料消耗量,定期测定全血乙酰胆碱酯酶(AChE)活性,实验结束时全部动物断头处死,测定延髓AChE活性,反相高效液相色谱荧光法测定大脑皮质GABA含量,放射性配体受体结合法测定大脑皮质GABA_A受体的活性。[结果]实验期间,各染毒组动物全血AChE活性明显抑制,实验后期有所恢复。实验结束时,低、中、高染毒组延髓AChE活性分别约为对照组的78%、63%、42%。与对照组相比,中、高剂量组大脑皮质GABA含量明显降低(P<0.01);GABA_A受体的最大结合容量(maximum binding capacity,Bmax)低剂量组升高(P<0.05),中剂量组降低(P<0.05);各剂量组GABA_A受体的平衡解离常数(equilibrium dissociation constant,Kd)比对照组均有降低,但仅低、中剂量组差异有统计学意义(P<0.05)。[结论]乐果90d染毒过程中大脑皮质GABA含量、GABA_A受体功能都有所改变,可能参与了乐果慢性中毒过程中的非胆碱能机制。     

Memantine alleviates toxicity induced by dichlorvos in rats

The changes of N-methyl-D-aspartate (NMDA) receptor and protective efficacy of memantine (MEM) in rats poisoned with dichlorvos were studied. Dichlorvos evoked down-regulation of the affinity and density of [(3)H]MK-801 binding to NMDA receptor in the brain of rats receiving dichlorvos (15 and 25 mg/kg bw, i.p.). The binding capacity of NMDA receptor and acetylcholinesterase activity were determined at 4 h, 8 h, 16 h, 24 h and 48 h after treatment. When rats were given a different doses of MEM (5, 15 and 45 mg/kg bw) after poisoning (dichlorvos 25 mg/kg bw), the latency of onset of signs was postponed and the magnitude of muscular fasciculation was alleviated as the dose of MEM increased. The lower doses of MEM (5 and 15 mg/kg bw) could antagonize the dichlorvos-evoked down-regulation of NMDA receptor, while the highest dose (45 mg/kg bw) decreased the Bmax and Kd values of NMDA receptors. These results show the dichlorvos-evoked down-regulation of NMDA receptor might be self-regulation by the body to protect the central nervous system. MEM could antagonize the down-regulation of NMDA receptors, and alleviated signs of poisoning, especially reducing the magnitude of muscular fasciculation. We suggest that the role of NMDA receptor in organophosphates (OP) poisoning should receive more attention, and, that MEM treatment in acute OP poisoning, as a supplement to atropine and oxime, should be considered.     

Upregulation of glutamate receptor subtypes during alcohol withdrawal in rats

AIMS: To investigate glutamate receptor subtypes during alcohol withdrawal. METHODS: Rats were exposed to severe alcohol intoxication for 84 h and then decapitated at 0, 12 and 36 h after the last alcohol dose (n = 7 per group). Alcohol was administered five times a day by intragastric intubation. The densities of N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors were studied in membranes from the forebrain by using the specific ligands [3H]MK-801 and [3H]AMPA, respectively. RESULTS: Although no change in the maximal density (B(max)) of [3H]MK-801 binding sites was observed at the time of withdrawal, [3H]MK-801 binding was increased by 49% 12 h into the withdrawal reaction compared with the control group. At 36 h post alcohol the B(max) of the [3H]MK-801 binding was still increased by 24% compared with the control group; however, this difference was not statistically significant. When investigated at the time of withdrawal from chronic alcohol intoxication, no significant alterations in the B(max) of the [3H]AMPA binding was detected, but 12 h into the withdrawal reaction the [3H]AMPA binding was markedly increased by 94%. At 36 h post alcohol the [3H]AMPA binding had returned to control levels. No significant alterations in the dissociation constant (K(D)) of either [3H]MK-801 or [3H]AMPA binding was observed at any time point. CONCLUSIONS: NMDA and AMPA receptors are involved in the cerebral hyperactivity of alcohol withdrawal.     

The effect ofin vitro andin vivo ethylenbis dithiocarbamate fungicides on NMDA receptors in rat brain membranes

To determine whether the ethlenbisdithiocarbamate fungicides, zineb, manzeb and maneb affect the N-methyl-D-aspartate (NMDA) receptor in rat brain membranes, we performed a binding assay using [³H]MK-801, a noncompetitive NMDA receptor antagonist. Displacement studies were conducted using well washed membranes to exclude the effect of endogenous acidic amino acids on the binding of [³H]MK-801. In both the presence or absence of added glutamate and glycine in the assay buffer, the dose-response curve indicated that zineb enhanced the binding in a concentration range of 100–500 μM. However, the displacement curves indicated that manzeb and maneb inhibited the binding in a concentration range of 10–500 μM. The addition of 50 μM glutamate and glycine to the assay medium increased binding by 5–20% above the control in a concentration range of 0.1–100 μM. No rats injected with zineb, manzeb, maneb (100 mg/kg, ip) showed any characteristic toxic signs or any significant weight changes within 24 hrs. Estimation of [³H]MK-801 binding to unwashed membranes from intoxicated rat brains revealed no marked change in Bmax or Kd values for 24 hrs following fungicide administration.     

Altered cholinergic metabolism and muscarinic receptor linked second messenger pathways after chronic exposure to dichlorvos in rat brain

Chronic dichlorvos exposure (6 mg/kg b.wt/day) for a period of 8 weeks resulted in significant reduction in body weight gain of the male Wistar rats. However, the dietary intake remained unchanged in experimental animals following dichlorvos treatment. Activity of the synthesizing enzyme of acetylcholine (ACh) ie, choline acetyltransferase, was found to be significantly increased and the activity of hydrolyzing enzyme, acetyl cholinesterase (AChE), was inhibited in all the three brain regions studied. Chronic dichlorvos treatment also caused significant reduction in both high affinity (HA) and low affinity (LA) choline uptake (CU), with maximal effect being observed in the brain stem followed by cerebellum and cerebrum. Muscarinic receptor binding was significantly decreased in brain stem and cerebellum as reflected in the decreased receptor number (B(max)), without any change in the binding affinity (K(d)) of the receptors. Dichlorvos treatment caused marked inhibition in cAMP synthesis as indicated by decreased adenylate cyclase activity as well as cAMP levels in cerebrum, cerebellum and brain stem. Our study shows that organophosphates may interact with muscarinic receptor-linked second messenger system and this could be a potential mechanism for the neurotoxic effects observed after repeated exposure to low levels of organophosphates, which are unexplainable on the basis of cholinergic hyperactivity.     

Effects of chronic prenatal ethanol exposure on NMDA receptor number and affinity for [3H]MK-801 in the cerebral cortex of the young postnatal and adult guinea-pig

The objective of this study was to test the hypothesis that chronic prenatal ethanol exposure (CPEE) produces changes in the number and/or affinity of N-methyl-D-aspartate (NMDA) receptors in the cerebral cortex that are developmental-age-dependent. Timed, pregnant Dunkin-Hartley-strain guinea-pigs received oral intubation of one of the following regimens, given daily as two equally divided doses 2 h apart, from gestational day (GD) 2 to GD 67 (term, ~GD 68): (i) 4 g ethanol kg(-1) maternal bodyweight; (ii) isocaloric sucrose with pair feeding; or (iii) water. Maternal blood ethanol concentration was measured on GD 57 or 58 at 1 h after the daily dose, and was 51.1 +/- 8.5 mM (235 +/- 39 mg dL(-1); n = 8). At postnatal day (PD) 11 (pre-weaning) and PD 61 (adulthood), body, brain and cerebral cortical weights of the offspring were measured. The number of NMDA receptors and their affinity for [(3)H]MK-801 were measured in a crude cerebral cortical membrane preparation using saturation isotherm analysis to determine the B(max) and K(D). Chronic prenatal ethanol exposure decreased offspring brain and cerebral cortical weights at PD 11 and PD 61. At PD 11, there was no CPEE-induced change of [(3)H]MK-801 binding characteristics in the cerebral cortex. At PD 61, both B(max) and K(D) for [(3)H]MK-801 binding to cerebral cortical NMDA receptors were decreased by CPEE compared with the isocaloric sucrose/pair-fed and water treatment groups. Loss of cerebral cortical NMDA receptors and increased affinity of the remaining receptors for [(3)H]MK-801 in the adult guinea-pig, compared with no change in the number or affinity of these receptors in the young postnatal offspring, demonstrated that the effects of CPEE on these ionotropic glutamate receptors are developmental-age-dependent.     

Repeated ethanol treatment in adolescent rats alters cortical NMDA receptor.

Earlier we have reported that repeated ethanol treatment during adolescence causes long-lasting impairments in spatial learning and memory. The present study was undertaken to determine the cellular mechanisms underlying the persistent ethanol-induced cognitive dysfunction in adolescent male rats. Since in adult animals ethanol is known to affect the N-methyl-d-aspartate (NMDA) receptor-gated ion channel, the hypothesis tested here was that adolescent ethanol exposure modulates NMDA receptor (NR) regulation in the brain. Adolescent male rats were injected daily with ethanol (2g/kg intraperitoneally) for 5 consecutive days. Control rats received isovolumetric saline for the same number of days. Groups of control and experimental rats were sacrificed 7 days after the last ethanol/saline administration, and NR activity was measured in specific brain regions (frontal cortex, hippocampus) using the [(3)H]MK-801 binding assay. In addition, some rats were sacrificed and their brains were used to investigate changes in NR pharmacology by measuring specific NR2 subunits immunohistochemically. Compared to saline-treated controls, ethanol-treated rats showed significant increases in [(3)H]MK-801 maximal binding in the frontal cortex. This was associated with increased cortical NR2B subunit protein. [(3)H]MK-801 binding in the hippocampus was minimally affected. These results indicate that ethanol exposure during the adolescent period produces brain region-specific alterations in NR activity. These changes are different from those reported in literature for ethanol administration during the perinatal period or adulthood. Together, these data suggest that adolescence represents a unique stage in brain development in its long-term sensitivity to ethanol.     

Effect of tributyltin compound onN-methyl-D-aspartate (NMDA) receptors in brain of preweanling mice

Objective The aim of this study was to investigate the effect of tributyltin (TBT) compound onN-methyl-d-aspartate (NMDA) receptors in the brains of preweanling mice. Methods Pregnant ICR mice were exposed to TBT chloride at concentrations of 0, 15, and 50 ppm in water. Male offspring were sacrificed at 1, 2 and 3 weeks after birth. Mouse brain membranes were prepared from cerebral cortices, and the specific binding of [³H]MK-801 to an NMDA receptor was determined by radioligand binding assay. Results The mean body weight of preweanling mice of the 50 ppm dose group decreased by 17–25% (p<0.01) at 1, 2 and 3 weeks of age, compared with that of preweanling mice of the corresponding control group. The [³H]MK-801 binding level significantly decreased (p<0.05) in the 15 ppm F1 group at 1 week and in the 15 ppm and 50 ppm F1 groups at 3 weeks of age, compared with that in the corresponding control F1 group. Conclusions The exposure to TBT via placenta and dam's milk seriously affected not only the growth of preweanling mice, but also the F1 cerebral NMDA receptors involved in memory and learning.     

Subject Index to Volume 27

Growing male rats that weighed 120 ± 5 g were kept for 30 days on the following synthetic diets: high protein diet (HPD), 59% casein; high fat diet (HFD), 50% saturated fat; and normal diet (ND), 19% casein, 10% saturated fat, and 60% sucrose. Other essential dietary ingredients were included in all the diets. All animals were injected at the end of the 30–day period with parathion [10 mg/kg intraperitoneal (ip) injection as a single dose] or dichlorvos (30 mg/kg ip as a single dose) to compare the effect of dietary pretreatments on mortality from parathion and dichlorvos. A lower dose of parathion (7.5 mg/kg) and dichlorvos (20 mg/kg) was employed in another set of experiments to compare the spontaneous regeneration of plasma and red blood cell (RBC) cholinesterase (ChE) activity at 2 hr, 1 day, 3 days, and 5 days after administration of parathion or dichlorvos. The effect of these diets on hepatic microsomal oxidases was also determined. Results showed that diets per se did not affect initial plasma and RBC ChE activity. The HPD and HFD significantly protected against mortality from parathion but not from dichlorvos. Hepatic microsomal cytochrome P–450 and aminopyrine demethylase activity were unchanged, but aniline hydroxylase activity was increased significantly by HPD and HFD. Parathion oxidase in hepatic microsomes was significantly increased in rats fed HFD only. For the HPD, spontaneous regeneration of ChE diminished in RBCs in parathion-intoxicated rats and in plasma and RBCs of dichlorvos-intoxicated rats. The HFD did not affect ChE regeneration in plasma or RCBs of parathion-intoxicated rats, but significantly increased it in dichlorvos-intoxicated rats. There may be a reversible protein sequestration of both insecticides in growing rats fed HPD.