Effect of 5-azacytidine on rat liver alpha-fetoprotein gene expression

Neonatal rats given 5-azacytidine intraperitoneally (30 micrograms/animal/day) on days 1-5 postpartum had 55% lower serum alpha-fetoprotein levels on day 6 compared to saline injected controls. On day 14, alpha-fetoprotein levels were 4-fold lower in 5-azacytidine treated animals. Cytosol alpha-fetoprotein was proportionately reduced. There were no significant changes in liver to body weight ratio, total serum protein, and both serum and cytosol albumin levels. The molecular basis for decreased serum alpha-fetoprotein levels was found to be a reduced concentration of alpha-fetoprotein mRNA in the livers of 5-azacytidine injected animals. These results are discussed with respect to the effects of 5-azacytidine on DNA methylation and cell differentiation.     

Repeated corticosterone treatment attenuates behavioural and neuroendocrine responses to 8-hydroxy-2-(di-n-propylamino) tetralin in rats.

The effects of 5 day corticosterone treatment (50 mg/kg s.c.; 2 x daily) are investigated on the behavioural and neuroendocrine responses to a 5-HT-1A selective agonist, 8-hydroxy -2-(di-n-propylamino) tetralin (8-OH-DPAT) in rats. Daily corticosterone treatment decreased body weight and food intake. After 5 day treatment a drug challenge of 0.25 and 0.5 mg/kg 8-OH-DPAT given on the sixth day produced smaller forepaw treading but comparable head waeving, flat body posture and also hypothermia in 5 day corticosterone than 5 day saline injected rats. Hyperphagic effects of only 0.25 mg/kg 8-OH-DPAT were attenuated in 5 day corticosterone injected animals. The effects of 8-OH-DPAT on the increases of plasma corticosterone were markedly attenuated in the 5 day corticosterone injected animals. The findings may help towards an understanding of steroid-induced affective changes and psychosis.     

Histological changes in the gonad, skin, intestine and olfactory epithelium of artificially-matured male American eels, Anguilla rostrata (LeSueur)

Migratory (silver) male American eels were injected weekly for 5 weeks with human chorionic gonadotropin (hCG), salmon pituitary extract, hydrocortisone 21-hemisuccinate (cortisol), or saline to determine the effects of induced maturation on the histology of their gonads, skin, intestines and olfactory epithelia. Treatment with hCG induced full sexual maturity, salmon pituitary evoked only limited spermatogenesis, and neither hydrocortisone nor saline had any effect on the gonad. Eels injected with hCG and salmon pituitary experienced no changes in skin morphology, but the epidermal thickness of saline- and hydrocortisone-treated fish decreased. Intestinal morphology did not change in any of the treatment groups. Both the presumed sensory and non-sensory portions of the olfactory epithelium of hCG- and pituitary-treated males exhibited a decrease in thickness, structural degeneration, and non-significant reductions in mucous cell density. Some of these changes in maturing male eels are similar to those previously observed in maturing females but others are different; it appears likely that maturing Anguilla are sexually dimorphic and that these changes are adaptive and not artifacts of the hormone treatments.     

慢性吗啡处理及戒断后大鼠杏仁核中Parvalbumin的表达变化

目的:观察慢性吗啡处理及戒断后大鼠杏仁核中Parvalbumin(PV)的表达变化,为其功能的研究提供形态学依据。方法:将30只健康雄性SD大鼠随机分为吗啡依赖组和生理盐水对照组。吗啡依赖组大鼠腹膜腔注射吗啡,2次/d,起始剂量为5 mg/kg,逐日递增5mg,至第10d为50mg/kg;对照组注射同体积的生理盐水。于末次注射后动物分别存活3h、3 d和14d。用免疫组化方法和相对平均灰度值检测杏仁核内PV的表达。结果:在生理盐水处理组各存活时间点,杏仁核内PV的表达相同。和生理盐水对照组相比,3h时杏仁核内PV的表达明显增加(P<0.05)。第3d时,杏仁核内PV的表达减少,明显低于第3 h组(P<0.05)。至第14d时,PV的表达又开始增加,明显高于第3 d组(P<0.05)。结论:本结果提示慢性吗啡处理及戒断后杏仁核PV的表达具有时相特异性;这种变化在戒断早期可能主要与躯体依赖相关,而戒断晚期主要与精神依赖相关。     

Transfer of conditioned reflex hypoglycemia in dogs

Conditioned hypoglycemia was induced by intravenous injection of a 20% glucose solution to donor dogs. In control tests the dogs were injected the same volume of 0.9% saline. Then 0.5 ml of cerebrospinal fluid from donor animals was injected into suboccipital cisterna of recipient dogs. 24 hours later the recipient animals were exposed to the conditioned signal and injected physiological saline. It has been demonstrated that hypoglycemic response in recipient and donor dogs was identical, the reactions retained in the recipient dogs for 5-7 days after the liquor administration.     

氯胺酮对抑郁大鼠模型抗抑郁作用研究

目的:探讨在抑郁大鼠模型中单次氯胺酮可产生快速持久地抗抑郁作用。方法:实验一:32只Wistar大鼠随机分为四组(n=8),药物干预前1 d大鼠强迫游泳15 min,药物干预当天,分别腹腔注射相同容积的生理盐水(S组)、5 mg/kg氯胺酮(K5组)、10 mg/kg氯胺酮(K10组)、15 mg/kg氯胺酮(K15组)。30 min后记录大鼠运动能力及不动时间。实验二:20只Wistar大鼠随机分为两组(n=10),所有大鼠均经历21天慢性不可预知应激试验。第22天大鼠分别腹腔注射相同容积生理盐水及10 mg/kg氯胺酮,于干预前、干预后1 h、2 h、6 h、1 d、4 d、7 d分别进行敞箱试验,并记录大鼠水平运动及垂直运动得分。结果:与S组相比,K5、K10及K15组大鼠运动能力无明显变化(P>0.05)且强迫游泳不动时间均显著减少(P<0.01);与干预前生理盐水组相比,生理盐水干预后1 h、2 h、6 h、1 d、4 d及7 d组大鼠敞箱试验水平运动及垂直运动均无明显差异(P>0.05);与干预前氯胺酮组相比,生理盐水干预后1 h、2 h、6 h、1 d、4 d及7 d组大鼠敞箱试验水平运动及垂直运动有明显差异(P<0.05)。结论:在抑郁症大鼠模型中氯胺酮可产生快速且持久的抗抑郁作用。     

Magnesium ions prevent development of hyperkinesis produced by picrotoxin intrastriatal microinjections into the rat neostriatum

The effects of daily bilateral microinjections of GABA-A receptor antagonist picrotoxin (2 mcg) into rostral neostriatum of the rats in chronic experiments were investigated. The picrotoxin was injected in volume of 1 mcl of saline or in 1 mcl of 1.0 M or 1.5 M MgCl2 solution; 1 mcl of saline or 1.0 M MgCl2 solution were injected in control groups of animals. The impairment of the avoidance conditioning in shuttle box, changes in free locomotor activity and the stereotypic choreo-myoclonic limb jerks were registered in rats with picrotoxin with the saline microinjections. The motor deviation registered are similar with Huntington chorea hyperkinesis in humans. The addition of magnesium ions into injected solution prevented both the lyperkinesis and condition behaviour realization impairment. As the magnesium is a universal calcium channel blocker, the calcium homeostasis of striatal neurons impairment as one of principal elements of hyperkinesis pathogenesis is proposed.     

Altered precursor availability and metabolism of monoamines in the brain caused by the injection of physiologic saline to suckling rats: On the reliability of saline “controls” in neurochemical studies

The effect of subcutaneous injections of saline (0.9% NaCl, 10–40 μl/g b. wt) to 5- and 20-day old rats on the concentrations of tyrosine (Tyr) and tryptophan (Trp) in the serum and the brain and on the levels of biogenic amines and their metabolites in the developing brain at 6 h p.i. is described. At day 5 the concentration of Tyr in the blood was decreased (dose-dependent), but the brain concentrations of Tyr and of its amine-metabolites, dopamine (DA), norepinephrine (NE), homovanillic acid (HVA) and dihydroxyphenylacetate (DOPAC) were unaffected. In contrast, in the 20-day old rat, serum Tyr was unaffected by the saline injections, but the Tyr concentration in the brain decreased markedly at the highest saline dose. The concentrations of NE (only at maximum dose) and of DA (independent on the amount of saline injected) were elevated in the brains of saline injected 20-day old rats. The concentrations of Trp and indoles were more affected at day 5 than at day 20: slightly decreased concentration of Trp in the serum but markedly increased concentrations of brain Trp (only at maximum dose), elevated serotonin (5-HT, independent on the amount of saline injected) and 5-hydroxyindoleacetic acid (5-HIAA, at maximum dose) in the brain. If the maximum dose of 40 μl/g body weight was injected to suckling rats repeatedly during the whole suckling period (in 12 h intervals), some effects caused by one single injection of 40 μl/g disappeared (Tyr—depletion in blood or brain, increase in brain NE, DA and Trp), but other additional effects appeared (decreased DA and increased DOPAC, decreased 5-HT and 5-HIAA). The results show that saline injections do cause characteristic, age-dependent alterations of precursor availability as well as of the rate of synthesis and degradation of catecholamine and 5-HT. Repeated treatments have different effects than one single treatment on the precursor availability and the metabolism of monoamines. These alterations must be taken into account if the effects of certain “specific” treatments are compared and discussed in relation to saline “controls”.     

灵芝多糖对顺铂引起的呕吐具抑制作用

以雄性昆明小鼠为实验材料,研究灵芝多糖对顺铂引起呕吐的抑制作用。实验分为5组,生理盐水+生理盐水组:腹腔注射0.9% NaCl两次,格拉司琼+顺铂组:腹腔注射格拉司琼和顺铂,生理盐水+顺铂组:腹腔注射0.9% NaCl和顺铂,灵芝多糖+生理盐水组:腹腔注射灵芝多糖和0.9% NaCl,灵芝多糖+顺铂组:腹腔注射灵芝多糖和顺铂,两种成分的注射间隔为30min。上述处理每天1次,连续5d,比较各组小鼠对高岭土的摄取量和脑内Fos蛋白表达水平。结果显示:顺铂可增加小鼠高岭土摄取量和脑内Fos蛋白表达水平,而格拉司琼和灵芝多糖可减少小鼠对高岭土的摄取量并降低脑内Fos蛋白表达水平。因此认为灵芝多糖可有效抑制顺铂引起的恶心呕吐。     

Short-term tolerance to morphine: Effects of indomethacin

Short-term tolerance to opiates has been demonstrated in as little as three hours after priming with a single dose of morphine in naive animals. Tail-flick latency in mice and changes in plasma corticosterone in rats were the indicators tested in these experiments. Rats primed with either saline or morphine, 10 mg/kg, were injected 3 hrs. subsequently with morphine, 5 mg/kg. Those primed with saline showed the characteristic plasma corticosterone elevation following morphine, when serial blood samples were examined, whereas those previously treated with morphine did not. Mice were primed with saline or either of two doses of morphine, 30 or 100 mg/kg, 3.5 hrs. prior to estimation of tail-flick latency and ED 50 determinations. Mice primed with either dose of morphine had significantly higher ED50's than those primed with saline. The effects of indomethacin, 5 or 10 mg/kg, were examined on both systems. Rats and mice were pretreated with indomethacin at 2.25 or 3 hrs., respectively, before morphine-priming. In all cases, indomethacin did not produce alterations in responses previously observed in correspondently treated controls.     

Extended function of the corpus luteum and earlier development of the second follicular wave in heifers treated with bovine somatotropin

Effects of recombinant bovine somatotropin (bST) on growth of the corpus luteum (CL) and development of ovarian follicles were tested. Starting at estrus (Day=0), the following treatments were administered: control (saline injected Days 0 to 19, n=5); bST[0-9] (25 mg bST injected Days 0 to 9, saline injected Days 10 to 19, n=5); bST[10-19] (saline injected Days 0 to 9, 25 mg bST injected Days 10 to 19, n=5); and bST[0-19] (25 mg bST injected Days 0 to 19, n=6). Blood was collected daily for progesterone analysis, and ultrasound examinations were performed daily for measurement of follicles and CL. Compared with the heifers treated with saline, those treated with bST had larger CL and more progesterone during the early (/=10 mm) follicles was greater (P<0.01) and largest follicles were smaller (P<0.001) in bST than in saline-treated heifers. Estrous cycle length and ovulation rate were similar for each group. In conclusion, bST increased initial development of the CL and extended its function. Furthermore, the second follicular wave was earlier with bST.     

Cadmium-Induced Oxidative Stress in the Rat Testes: Protective Effects of Betaine

The aim of the present study was to evaluate the antioxidant effects of betaine against oxidative stress and pathological changes mediated by cadmium in the testes of rats. The adult male Wistar rats were allocated into three experimental groups as follows: the cadmium group received cadmium chloride at the dosage of 2 mg/kg intraperitoneally thereafter, the rats treated by physiological saline for 10 consecutive days. The betaine plus cadmium group received betaine at the dosage of 1.5 % w/w of the total diet orally for 10 consecutive days and cadmium chloride injected at the 2nd day of the betaine treatment. The control rats were injected physiological saline. Both testes of rats were removed for antioxidant assay and pathological changes evaluation on days 5 and 10 after cadmium toxicity. TBARS concentration (as a lipid peroxidation marker) was significantly higher in the cadmium group by day 10 compared to control and betaine plus cadmium groups, and it was significantly higher in cadmium group by day 5 in comparison with the controls. Catalase (CAT) and glutathione peroxidase activities decreased significantly by day 10 in cadmium group when compared to the controls. In contrast, CAT and superoxide dismutase activities increased significantly by day 10 in betaine plus cadmium group when compared to the cadmium group. In addition, the antioxidant effects of betaine could prevent testicular pathological changes in betaine plus cadmium group. The present data allow us to exploit the advantages of this nutrient agent in future studies.     

Effects of chronic methamphetamine exposure on heart function in uninfected and retrovirus-infected mice

Methamphetamine (MA) increases catecholamine levels, which have detrimental effects on heart function through vasoconstriction, myocardial hypertrophy, and fibrosis. Murine retrovirus infection induces dilated cardiomyopathy (DCM). The present study investigated the cardiovascular effects of chronic MA treatment on uninfected and retrovirus-infected mice. C57BL/6 mice were studied after 12 weeks treatment. The four study groups were (group I) uninfected, MA placebo; (group II) infected, MA placebo; (group III) uninfected, MA treatment; and (group IV) infected and MA treatment. MA injections were given i.p. once a day for 5 days/week with a increasing dose from 15 mg/kg to 40 mg/kg. Left ventricular mechanics were measured in situ a using Millar conductance catheter system for pressure-volume loop analysis. Cardiac pathology was determined with histological analysis. In the uninfected mice, the load independent contractile parameters, pre-load recruitable stroke work (PRSW) and dP/dt(max) vs. Ved, significantly decreased by 32% and 35% in MA treated mice when compared to the saline injected mice. In retrovirus-infected mice, although there were no significant difference in Ees, PRSW, and dP/dt(max) vs. Ved due to MA treatment, they were increased 45%, 15% and 42% respectively when compared to saline treated mice. No further lowered heart function during murine AIDS may be due to the counteraction of the retroviral DCM and the MA induced myocardial fibrosis and hypertrophy (thickening of the ventricular walls). This is supported by increases in the End-diastolic volume (Ved, 38%) and End-systolic volume (Ves, 84%) in the retrovirus-infected saline injected mice, the decreases of 33% and 17% in the uninfected MA-treated mice, but no significant changes in the retrovirus-infected MA treated mice when compared to uninfected saline injected mice. These data suggest that MA induced myocardial cellular changes compensate for retrovirus induced DCM.     

大鼠薄型子宫内膜模型的建立和鉴定

为探索宫腔注入无水乙醇建立薄型子宫内膜模型的可行性,将25只大鼠分3组:对照组(宫腔注入生理盐水),5分钟组(宫腔注入无水乙醇并贮留5 min),10分钟组(宫腔注入无水乙醇并贮留10 min),经测量子宫内膜变薄者为造模组,5分钟组有14个子宫内膜变薄,10分钟组无一例纳入造模组.免疫组织化学检测角蛋白、波形蛋白、血管内皮生长因子(vascular endothelial growth factor,VEGF)、雌激素受体α(estrogen related recep-tor alpha,ERα)的表达.结果发现5分钟组造模组与对照组单位内膜面积中角蛋白面积、单位间质面积中波形蛋白面积和子宫内膜中VEGF平均光密度差异有统计学意义(P<0.05),造模组与对照组子宫内膜ERα组织学积分无差异(P>0.05).表明宫腔注入无水乙醇并贮留5 min可以成功建立薄型子宫内膜模型,成功率为70%.     

Analgesic effect of tianeptine in mice

The effects of tianeptine, a novel and unusual tricyclic antidepressant drug, on tail-flick and hot-plate tests, which are two thermal analgesia evaluating methods, have been investigated in mice. Tianeptine (5 and 10 mg/kg), para-chlorophenylalanine (pCPA) (100 mg/kg) and a combination of pCPA and tianeptine (10 mg/kg) or saline were injected to mice intraperitoneally. pCPA (100 mg/kg) was injected 24 h before tianeptine or saline treatment when it was combined with tinaeptine (10 mg/kg) or tested alone. The tail-flick latencies and hot-plate reaction times of the mice were measured between 15th and 180th minutes following injections. Tianeptine (10 mg/kg) exhibited a significant antinociceptive activity that could be measured by both tests as compared to groups which were treated with saline or pCPA alone between 15th and 180th min of the observation period. The lower dose of tianeptine (5 mg/kg) or pCPA (100 mg/kg) did not produce any significant changes on tail-flick latency or hot-plate reaction time of the mice. However, pretreatment with pCPA completely blocked the antinociceptive effect induced by tianeptine (10 mg/kg) in both tests used in the present study. Furthermore, tianeptine (10 mg/kg) did not cause any significant impairment effects on rotarod performance of the mice. Our results suggested that tianeptine has a prominent thermal antinociceptive activity in mice and that increased serotonergic activity may be responsible for the analgesic effect of tianeptine.     

对比剂注射方式对下肢动脉血管成像质量的影响

目的:探讨对比剂不同注射方式对下肢动脉血管成像(CTA)质量的影响。方法:选择2013年6月到2015年10月在我院怀疑下肢动脉栓塞或狭窄而行CTA检查的患者80例,按随机数字表法分为A、B两组,各40例。A组患者先以5 mL/s的速率注射100 mL优维显,后以5 mL/s的速率注射50 mL生理盐水。B组患者先以5 mL/s的速率注射50 mL优维显,后以2.5 mL/s的速率注射50 mL优维显,最后以5 mL/s的速率注射50 mL生理盐水。比较两组患者的下肢动脉CTA图像质量。结果:B组患者不同横断面CT值相比于A组较平稳(P0.05)。B组患者小腿动脉和足部动脉的边缘分级、血管分支等级评价及显示的节段数均明显高于A组(P0.05)。结论:对比剂以不同速率相结合的注射方式能够使下肢动脉血管中对比剂浓度维持在平稳且较高的水平,可以提高下肢动脉CTA图像质量,值得在临床上推广应用。     

沙利度胺对实验性矽肺血管生成的干预研究

目的观察实验性矽肺形成过程中肺组织局部血管生成的动态变化,以及沙利度胺对矽肺肺纤维化血管生成的干预作用。方法SD大鼠54只,随机分为3组,矽肺组和沙利度胺组气管内注入二氧化硅混旋液复制实验性大鼠矽肺模型,对照组在相同条件下给予生理盐水。第二天起沙利度胺组给予沙利度胺饲料喂养,其余各组在相同条件下给予普通饲料喂养。采用HE染色、羟脯氨酸含量测定、免疫组织化学染色等方法,观察实验性大鼠矽肺的发病过程,肺组织中p-Akt蛋白和局部血管生成的动态变化及其与肺胶原蛋白含量的关系。结果矽肺组第7天新生血管明显增多,第30天较第7天有所减少,到第60天肺组织正常结构基本消失,取代为广泛结节性纤维化,少见血管;沙利度胺组血管生成在第7天轻于矽肺组,但仍高于对照组。免疫组化显示p-Akt蛋白在矽肺组第7天明显达到高峰,第30天时较第7天有所减弱,第60天时明显减弱。沙利度胺组p-Akt蛋白和羟脯氨酸含量均低于矽肺组,但高于对照组。结论矽肺早期血管生成显著,血管生成在矽肺肺纤维化发生早期可能起重要作用;沙利度胺能在一定程度上抑制过度的血管生成,对实验性矽肺具有一定的阻抑作用。     

Prostaglandin-induced regression of porcine corpora lutea maintained by estrogen.

Corpora lutea were marked with suture in 24 crossbred gilts on day 7 to 9 of the estrous cycle (first day of estrus equals 0). All gilts were injected with 5 mg of estradiol benzoate (EB) daily from day 10 to 15 to extend the lifespan of corpora tutea, then the gilts were randomly assigned to two groups. On day 20, the 12 gilts of Group 1 were injected with 10 mg PGF-2ALPHA, and the 12 gilts of Group 2 were injected with saline. Ovaries were recovered 10 to 13 days after PGF-2ALPHA or saline injection. Ten gilts in Group 1 displayed estrus 5 plus or minus 0.7 days after PGF-2ALPHA injection, but only two gilts in Group 2 displayed estrus during the experimental period. In gilts that displayed estrus, all marked CL had regressed. Marked CL were still present in all 12 gilts that failed to exhibit estrus during the experimental period. These results show that in the pig, PGF-2ALPHA caused regression of CL that were maintained beyond the normal luteal phase of the estrous cycel by EB treatment.     

Measurement of serum prolactin and the effect of ketamine anesthesia on serum prolactin levels in cynomolgus monkeys (Macaca fascicularis)

The effect of an anesthetic, ketamine, on the serum prolactin level was examined in wild-originating female cynomolgus monkeys (Macaca fascicularis) imported from South East Asia. Serum prolactin levels were measured by the homologous radioimmunoassay system which was developed for human prolactin. The validity was confirmed by using an extract of pituitary gland from a female cynomolgus monkey as well as serum and amniotic fluid from a pregnant monkey. Additionally, serum luteinizing hormone (LH) levels were determined by the radioreceptor assay system developed in our laboratory using Leydig cells collected from rat's testes as a receptor fraction. The experiment was repeated three times at one-month interval, using twenty animals that were divided into three groups consisting of 5, 7 and 8 monkeys each. In the first experiment, the first group was injected with physiological saline and the second and third groups were intramuscularly given ketamine at a dose level of 5 mg/kg B.W. and 15 mg/kg B.W., respectively. In the second experiment, the first and second groups were given ketamine at a dose of 5 mg/kg B.W. and of 15 mg/kg B.W., respectively, and the third group was served as control injected with saline. In the third experiment, the first and third groups were administered with 15 mg/kg and 5 mg/kg of ketamine and the second group was injected with saline. In short, all of the twenty monkeys received the three different treatments for two months. The serum prolactin level showed a marked increase after the administration of ketamine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of cyclophosphamide and buthionine sulfoximine on ovarian glutathione and apoptosis

Treatment with the anticancer drug cyclophosphamide (CPA) destroys ovarian follicles. The active metabolites of CPA are detoxified by conjugation with glutathione (GSH). We tested the hypotheses that CPA causes apoptosis in ovarian follicles and that suppression of ovarian GSH synthesis before CPA administration enhances CPA-induced apoptosis. Proestrous rats were given two injections, 2 h apart, with (1) saline, then saline; (2) saline, then 50 mg/kg CPA; (3) saline, then 300 mg/kg CPA; or (4) 5 mmol/kg buthionine sulfoximine (BSO) to inhibit glutamate cysteine ligase (GCL), the rate-limiting enzyme in GSH synthesis, and then 50 mg/kg CPA. Statistically significantly increased DNA fragmentation by agarose gel electrophoresis and granulosa cell apoptosis by TUNEL were observed in the CPA-treated ovaries 24 h after the second injection, but BSO did not enhance the effect of 50 mg/kg CPA. We next tested the hypothesis that CPA depresses ovarian GSH concentration and expression of the rate-limiting enzyme in GSH synthesis, GCL. Proestrous rats were injected with 300 or 50 mg/kg CPA or vehicle and were sacrificed 8 or 24 h later. After CPA treatment, ovarian and hepatic GSH levels decreased significantly, and ovarian GCL subunit mRNA levels increased significantly. There were no significant changes in GCL subunit protein levels. Finally, we tested the hypothesis that GSH depletion causes apoptosis in ovarian follicles. Proestrous or estrous rats were injected with 5 mmol/kg BSO or saline at 0700 and 1900 h. There was a significant increase in the percentage of histologically atretic follicles and a nonsignificant increase in the percentage of apoptotic, TUNEL-positive follicles 24 h after onset of BSO treatment. Our results demonstrate that CPA destroys ovarian follicles by inducing granulosa cell apoptosis and that CPA treatment causes a decline in ovarian GSH levels. More pronounced GSH suppression achieved after BSO treatment did not cause a statistically significant increase in follicular apoptosis. Thus, GSH depletion does not seem to be the mechanism by which CPA causes follicular apoptosis.