Propolis protection from reproductive toxicity caused by aluminium chloride in male rats

Different forms of aluminium (Al) are environmental xenobiotics that induce free radical-mediated cytotoxicity and reproductive toxicity. Propolis has been reported to be important antioxidant. Therefore, this study aimed at elucidating the protective effects of propolis against reproductive toxicity of aluminium chloride (AlCl₃) in male rats. The first group served as control. Group 2 received 34 mg AlCl₃/kg bw (1/25 LD₅₀). Group 3 was administered 50 mg propolis/kg bw/day. Group 4 was treated with AlCl₃ plus propolis. Treatment was continued for 70 days. AlCl₃ caused a decrease in testes, seminal vesicle and epididymis weights, sperm concentration, motility, testosterone level and the activities of 17-ketosteroid reductase, CAT and GST, and GSH content. While, dead and abnormal sperm and testes TBARS concentrations were increased. In the AlCl₃-treated group, histopathologic examinations revealed apparent alterations in the testes, where it induced marked lesions in seminiferous tubules. Propolis alone decreased dead and abnormal sperm and TBARS, and increased testosterone, GSH, 17-ketosteroid reductase, CAT and GST. Results showed that propolis antagonized the harmful effects of AlCl₃. This was proved histopathologically by the great improvement in testes. In conclusion propolis could be effective in the protection against the reproductive toxicity of AlCl₃.     

Protective effects of testosterone propionate on reproductive toxicity caused by Endosulfan in male mice

To investigate the protective effect of testosterone propionate (TP) on reproductive toxicity caused by endosulfan in male mice, three group experiments were designed: the control group received 0 and 0, the endosulfan group received 0.8 and 0, and the endosulfan + TP group received 0.8 mg/kg/d endosulfan and 10 mg/kg/d TP, respectively. The results showed that TP significantly prevented the declines of concentration and motility rates in sperm, reduced the rate of sperm abnormalities in epididymis; and antagonized the decreases in spermatogenous cell and sperm numbers in testes induced by endosulfan. TP also decreased the numbers of cavities formed, prevented the decreases of plasma testosterone and androgen receptor (AR) mRNA in testicular tissue, alleviated the increase of LH induced by endosulfan. It is likely that TP relieve the reproductive toxicity by reversing the endosulfan‐induced decreases in testosterone secretion and AR expression that resulted from the alteration of Leydig cell function. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 142–153, 2016.     

The effects of carbon disulfide on the reproductive system of the male rat

Two experimental protocols were employed to determine the effects of carbon disulfide (CS₂) on the reproductive system of the male rat. In the first experiment, adult Long Evans hooded rats were exposed to 0,350 or 600 ppm CS₂ vapor for 10 weeks (5 h/day, 5 days/week). CS₂ exposure caused no change in reproductive organ weights nor in plasma gonadotropin levels. However, animals exposed to 600 ppm CS₂ had slightly lower epididymal sperm counts and significantly reduced plasma testosterone levels. In order to determine if monitoring hormone levels and sperm status in the same male over time might increase the sensitivity of detecting a toxic reaction, the second protocol was employed. Male rats were exposed to 0 or 600 ppm CS₂. After 0, 1, 4, 7 and 10 weeks of exposure, males were observed for mating behavior, and ejaculated sperm count and plasma hormone levels were determined. Animals exposed to 600 ppm CS₂ had significantly shorter times to mount and to ejaculate and decreased ejaculated sperm counts. Plasma gonadotropin levels were similar in both groups while plasma testosterone levels were marginally depressed in CS₂-exposed animals in the early weeks. These data indicate that CS₂ is a toxin of the male reproductive system resulting in abnormal coital behavior and decreased sperm counts. The second experimental protocol proves to be a sensitive method for assessing adverse effects in the male reproductive system.     

Comparison of reproductive toxicity caused by cisplatin and novel platinum-N-heterocyclic carbene complex in male rats

Cisplatin and other platinum complexes are important chemotherapeutic agents and useful in the treatment for several cancers such as prostate, ovarian and testis. However, severe side effects including reproductive toxicity of cisplatin and other platinum complex cause limitations in their clinical usage. In this context, we aimed to compare the damage in testis caused by cisplatin and a novel platinum-N-heterocyclic carbene complex (Pt-NHC). To this end, 35 Sprague-Dawley rats were divided randomly into five equal groups (n = 7 in each group). Cisplatin and Pt-NHC were intraperitoneally administered as a single dose of 5 mg/kg or 10 mg/kg, and the rats were then killed 10 days after this treatment. The testicular tissues and serum samples were taken from all rats for the determination of reproductive toxicity. The results showed that cisplatin and Pt-NHC caused toxicity on the reproductive system via increased oxidative and histological damage, decreased serum testosterone levels and negatively altered sperm characteristics in a dose-dependent manner (p < 0.05). At the same dose levels, cisplatin generally caused lower toxicity on the reproductive system compared with Pt-NHC. In conclusion, these results suggest that Pt-NHC has more toxic effects on the male reproductive system than cisplatin, and in terms of clinical usage, Pt-NHC may be unsafe compared with cisplatin.     

二硫化碳的大鼠肾脏毒性

ＣＳ２亚急性动物染毒实验结果发现：各染毒组大鼠尿ＡＫＰ活性均较对照组增高（Ｐ＜０．０１或Ｐ＜０．０５）；１２５０ｍｇ／ｍ３染毒组大鼠红细胞ＬＰＯ较对照组升高（Ｐ＜０．０１）；红细胞和肾组织匀浆ＳＯＤ活性随染毒剂量增高呈先上升后下降的变化；１２５０ｍｇ／ｍ３染毒组大鼠肾组织近曲小管上皮细胞浊肿，线粒体肿胀变性。提示ＣＳ２所致肾损害似与组织细胞自由基引发脂质过氧化有关。     

Protective effects of tripterygium glycoside-loaded solid lipid nanoparticles on male reproductive toxicity in rats

The protective effects of tripterygium glycoside-loaded solid lipid nanoparticles (TG-SLNs) on male reproductive toxicity were investigated in rats. Thirty-six male Sprague-Dawley rats were randomly divided into three groups of 12: control group, tripterygium glycoside (TG) group, and TG-SLN group. After the animals had been orally administered with the substances for 28 consecutive days, their sperm count and sperm motility, organ coefficients, serum testosterone levels, testicular ultrastructure, and reproductive ability were observed. The results showed that the sperm motility rate in the TG group was only 3%, whereas the rates in the TG-SLN and control groups were 33% and 71%, respectively. Compared with those in the control group, the motion counts of path velocity, track speed, progressive velocity, straightness, linearity, beat cross frequency, amplitude of lateral head displacement, and sperm concentrations in the TG-SLN group were not significantly different while those in the TG group significantly decreased (p < 0.01). TG-SLNs did not cause testicular atrophy and instead maintained normal serum testosterone levels. The effect of TG-SLNs on the testicular ultrastructure was very evident; the morphologies of Sertoli, spermatogonial, mitochondrial, and sperm cells were normal. In terms of reproductive ability, one rat (17%) from the TG-SLN group and five rats (83%) from the control group became pregnant, whereas none of the rats from the TG group became pregnant. These data indicate that TG-SLNs have potentially protective effects on male reproductive toxicity in rats.     

Allethrin toxicity causes reproductive dysfunction in male rats

Pyrethroids are widely used for domestic and agricultural purposes and their use is increasing, especially in developing countries. Uncontrolled use of these insecticides resulted in their entry into the food chain thereby causing toxicity to different organ systems. Allethrin is one of the widely used pyrethroids, but its toxicological effects are underreported when compared to other pyrethroids. Further, its effects on the male reproductive tract remain uncharacterized. In this study, its toxicity on the male reproductive tract was evaluated by administering 25–150 mg/kg body weight allethrin to adult rats for 60 days. The mRNA expression of factors that are important in spermatogenesis (Scf, c‐Kit, Hsf2, Ovol1, Brdt, Kdm3A, Ybx‐2, and Grth) and steroidogenesis (StAR, 3β‐HSD, 17β‐HSD) was significantly downregulated. Decreased levels of testosterone, reduced sperm count and daily sperm production was also observed due to allethrin toxicity. However, sperm quality parameters assessed by computer‐assisted sperm analyzer were not affected. Spermatozoa obtained from allethrin‐treated rats failed to undergo acrosome reaction. Results of this study indicate that allethrin affects spermatogenesis and sperm function, thus lending further support to the growing evidence of its toxicity.     

Indium acetate toxicity in male reproductive system in rats

Indium, a rare earth metal characterized by high plasticity, corrosion resistance, and a low melting point, is widely used in the electronics industry, but has been reported to be an environmental pollutant and a health hazard. We designed a study to investigate the effects of subacute exposure of indium compounds on male reproductive function. Twelve‐week old male Sprague‐Dawley rats were randomly divided into test and control groups, and received weekly intraperitoneal injections of indium acetate (1.5 mg/kg body weight) and normal saline, respectively, for 8 weeks. Serum indium levels, cauda epididymal sperm count, motility, morphology, chromatin DNA structure, mitochondrial membrane potential, oxidative stress, and testis DNA content were investigated. The indium acetate‐treated group showed significant reproductive toxicity, as well as an increased percentage of sperm morphology abnormality, chromatin integrity damage, and superoxide anion generation. Furthermore, positive correlations among sperm morphology abnormalities, chromatin DNA damage, and superoxide anion generation were also noted. The results of this study demonstrated the toxic effect of subacute low‐dose indium exposure during the period of sexual maturation on male reproductive function in adulthood, through an increase in oxidative stress and sperm chromatin DNA damage during spermiogenesis, in a rodent model. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 68–76, 2016.     

Mechanisms involved in reproductive toxicity caused by nickel nanoparticle in female rats

Nickel nanoparticles (Ni NPs) are associated with reproductive toxicity. However, the mechanisms of reproductive toxicity are unclear. Our goal was to explore further reproductive toxicity induced by nickel nanoparticle and mechanisms involved in this process, including the role of oxidative stress and apoptosis. According to the one‐generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including ultrastructural, reactive oxygen species (ROS), oxidant and antioxidant enzymes, and cell apoptosis‐related factors. Ultrastructural results of ovaries showed mitochondrion swelling, disappearance of mitochondrial cristae, and enlargement of the endoplasmic reticulum in the exposure groups. NiNPs had significantly decreased the activity of SOD and CAT, and had increased the levels of ROS, MDA, and NO in comparison with the control groups. The mRNA expressions of caspase‐3, caspase‐8, and caspase‐9 and the expressions of Fas, Cyt c, Bax, and Bid protein on the ovaries significantly increased. At the same time, the expressions of Bcl‐2 protein were significantly decreased. Based on these results, oxidative stress and cell apoptosis may play the important roles in inducing reproductive toxicity after NiNPs treatment. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1674–1683, 2016.     

Nitric oxide mediated venodilator effects of nebivolol.

1. Nebivolol, a selective beta 1-adrenoceptor antagonist with antihypertensive effects, has haemodynamic effects suggestive of a direct vasodilator action. 2. The dorsal hand vein technique was used to determine whether nebivolol has venodilator action in vivo in man. 3. Nebivolol and atenolol were infused into the phenylephrine preconstricted superficial hand veins of 11 healthy male volunteers. In separate studies L-NMMA (0.1 microgram min-1) was pre- and co-infused with nebivolol to determine whether nitric oxide (NO) mediated mechanisms were present. Further studies with prostaglandin F2 alpha (PGF2 alpha) preconstriction were performed to exclude an alpha-adrenergic antagonistic effect of nebivolol. Effects of L-NMMA infusion on nitroglycerin venodilation were also determined. 4. Nebivolol produced a dose dependent venodilation, (72 +/- 18% maximum), whereas atenolol produced no significant venodilation. At doses of nebivolol producing plasma concentrations comparable with plasma levels achieved after standard oral dosing (10(-13)-10(-12) mol min-1) small (14 +/- 6% and 23 +/- 8%) but significant (P < 0.05) venodilation was observed. 5. The venodilator response to nebivolol was significantly reduced by infusion of L-NMMA (maximum dilation 18% vs 72%, P < 0.01). Venodilator responses to nitroglycerin were unaffected by L-NMMA infusion. A venodilator effect to nebivolol was also seen following preconstriction with PgF2 alpha (40 +/- 20% maximum). 6. Nebivolol has nitric oxide mediated, venodilator effects in man.     

Prolonged administration of proguanil induces reproductive toxicity in male rats

The toxicity of proguanil was studied on reproductive activities in male rats using in vivo and in vitro methods. Groups of ten to twelve-week-old rats were administered proguanil (2.9 mg/kg body weight) daily for 5 days and 6 weeks respectively. Thereafter, body and reproductive organ weights were taken, sperm parameters were analyzed, while the histology of the testis and epididymis were carried out. Also, serum levels of testosterone, luteinizing hormone and follicle stimulating hormone were determined. Sertoli cells obtained from sixteen to eighteen day-old-rats were cultured and treated with 0.3 μM to 10 μM of proguanil for 5 days after which Sertoli cell viability and nuclei integrity were determined. Also, the genetic expressions of transferrin and Glial cell line-derived neurotrophic factor (G.D.N.F.) were assessed. The data obtained were analyzed using the analysis of variance (ANOVA) with Students-Newman-Keuls multiple comparison test. The results showed duration dependent significant decrease in body and organ weights and also in sperm parameters. Serum testosterone level was significantly decreased while luteinizing hormone and follicle stimulating hormone showed no significant change. Duration dependent degeneration was also observed in the testis and epididymis of treated rats. These changes were restored in recovery experiment. Viability and DNA integrity of treated Sertoli cells reduced in a dose and duration dependent manner. However, the genetic expressions of transferrin and Glial cell line-derived neurotropic factor were normal. These results show that proguanil could induce infertility in rats which may act by distorting the blood-testis barrier formed by the Sertoli cells.     

壬基酚对雄性仔鼠生殖毒性的研究

目的 探讨孕鼠暴露壬基酚对雄性仔鼠生殖系统的影响.方法 大鼠妊娠第14～19 d灌胃染毒壬基酚(20、40,80、200 mg/ks),仔鼠90 d龄剖杀,检测与生殖功能相关各项指标.结果 与阴性对照组比较,80～200 mg/kg组睾丸、前列腺重量及脏器系数,精子活动度、附睾尾精子计数、睾丸每日精子生成量和血清睾酮均显著下降;碱性磷酸酶(ALP)和乳酸脱氢酶(LDH)活力与染毒剂量呈负相关.结论 孕鼠暴露80 mg/kg壬基酚可危害F,雄性仔鼠某些生殖功能.     

Mitochondrion-mediated apoptosis is involved in reproductive damage caused by BPA in male rats

Bisphenol A (BPA) is a widely used environmental endocrine disruptor. Many studies have reported that BPA exposure shows reproductive toxicity and causes apoptosis in spermatogenic cells. However, few studies have investigated the relationship between the mitochondrial pathway and BPA-induced apoptosis. This study investigated the role of the mitochondrial pathway in apoptosis induced by BPA, which resulted in compromised male rat spermatogenesis and reproductive damage. Rats were exposed to various BPA concentrations (0, 50, 100, or 200 mg of BPA/kg body weight per day), and factors in the mitochondrial signal transduction pathway and the apoptosis indices of spermatogenic cells were measured and sperm characteristics were analyzed. Our data revealed that BPA exposure increased the protein and mRNA levels of cytochrome C, apoptosis-inducing factor, caspase-3/9, and Bax; caspase-3 and caspase-9 activities; and the apoptosis indices of spermatogenic cells. In addition, abnormal structure of mitochondria and decreased protein and gene levels of Bcl-2 were observed following BPA exposure. These results suggest that apoptosis in the mitochondrial pathway mediates compromised reproductive system function caused by BPA exposure.     

Sublethal effects of zinc oxide nanoparticles on male reproductive cells

Environmental exposure to nanomaterials is inevitable as nanomaterials become part of our daily life, and as a result, nanotoxicity research is gaining attention. Most investigators focused on the effects of zinc oxide nanoparticles (ZnO NPs) on human health, while limited information was available on the male reproductive system. Herein, mouse Sertoli cell line (TM-4) and spermatocyte cell line (GC2-spd) were used as in vitro models to explore the reproductive effects of ZnO NPs at sublethal dose and its underlying mechanisms. Cells were treated with different concentrations of ZnO NPs. By cell viability assay, a dose of 8 μg/mL was found as a sublethal dose and increased the ROS levels in both cells. The decreased glutathione level and increased MDA level were also found in ZnO NPs treated group. In TM4 cells, the expressions of BTB proteins (ZO-1, occludin, claudin-5, and connexin-43) were lower in the ZnO NPs group. The increased cell permeability and increased TNF-α secretion were also observed in ZnO NPs group. In GC2-spd cells, S phase arrest and DNA damage occurred in ZnO NPs group, which could be partially rescued by NAC. Our findings demonstrated that exposure to ZnO NPs induced ROS generation, caused DNA damage of germ cells, and down-regulated the expression of BTB proteins in Sertoli cells which could compromise the integrity of the blood-testis barrier. All these contributed to the male reproductive cytotoxic effects of ZnO NPs that could be partially rescued by anti-oxidants.     

Evaluation of the reproductive toxicity of patulin in growing male rats

Patulin is a mycotoxin produced by several Penicillium, Aspergillus and Byssachlamys species. Patulin can be produced on different food products including fruits, grains, cheese, cured meats, but in natural situations patulin is exclusively found in apple and apple products. Patulin, at dose of 0.1 mg/kg bw/day, was administered by gavage to the growing male rats aged 5–6 week for 60 or 90 days. At the end of the experiment, sperm counts and morphology were investigated. Also, effects of patulin on the epididymis, seminal vesicle and prostate tissues were examined histopathologically and morphologically.

While sperm counts increased in patulin-treated rats for 60 days, sperm counts in patulin-treated rats for 90 days decreased compared to the corresponding control group. Patulin affected sperm morphology of growing male rats. Tail abnormalities like bent and/or coiled tails, and sticking of sperm tails were observed. A significant change was not determined in absolute and relative weights of the seminal vesicle and prostate of patulin-treated rats. While absolute cauda epididymal weights increased in rats treated with patulin for 60 days, absolute and relative cauda epididymal weights reduced in rats treated with patulin for 90 days. In histologic examination, some histopathological changes were observed in the epididymis and prostate tissues of rats in patulin treatment groups.     

Two-generation reproductive toxicity study of tributyltin chloride in male rats.

A 2-generation reproductive toxicity study of tributyltin chloride (TBTCl) was conducted in male rats using dietary concentrations of 5, 25, and 125 ppm TBTCl to evaluate its effect on sexual development and the reproductive system. F1 males were killed on postnatal day 119 and F2 males were killed on postnatal day 91. TBTCl affected the male reproductive system of rats. The weights of the testis and epididymis were decreased and homogenization-resistant spermatid and sperm count were reduced mainly in the 125 ppm TBTCl group. Histopathologic changes were also observed in the testis of this group and included vacuolization of the seminiferous epithelium, spermatid retention, and delayed spermiation. However, the changes were minimal in nature. The weight of the ventral prostate was decreased to 84% of the control value in the 125 ppm group in the F1 generation and decreased to 84 and 69% of the control value in the 25 ppm and 125 ppm TBTCl groups, respectively, in the F2 generation. The serum 17beta-estradiol concentration was also decreased to 55% of the control value in the 125 ppm group in the F1 generation and decreased to 78 and 57% of the control value in the 25 ppm and 125 ppm TBTCl groups, respectively, in the F2 generation. However, the serum concentrations of luteinizing hormone (LH) and testosterone were not decreased in these groups. These changes corresponded with those caused by aromatase inhibition and therefore TBTCl might be a weak aromatase inhibitor in male rats.     

Assessment of dose-dependent reproductive toxicity of diclofenac sodium in male rats

Diclofenac sodium is widely used in the non-steroidal anti-inflammatory drug in the treatment of pain and inflammation. It is also particularly associated with its adverse effects on avian fauna and linked to environmental issues. The present study was aimed to assess the dose-dependent toxicity of diclofenac sodium on a male reproductive system of rats. Four groups of healthy adult fertile male rats were administered with saline (control) or 0.25?mg/kg, 0.50?mg/kg and 1.0?mg/kg of diclofenac sodium, respectively for 30 days. Alterations in body and organ weight, sperm and testicular cell population dynamics, serum biochemistry, histopathology, and hematology were investigated as per aimed objectives. Diclofenac sodium treatment significantly (p?≤?0.001) reduced weights of testis, epididymis, ventral prostate and seminal vesicle. Sperm count, sperm density (in epididymis and testis), sperm motility and testicular cell population dynamics were lowered in a dose-dependent manner. Administration of diclofenac exhibited varying degrees of degeneration testis, abnormal histo-architectures, and shrinkages in seminiferous tubules, particularly in higher doses. Diclofenac sodium treatments also altered hepatic and renal function parameters significantly. In conclusion, it may claim that diclofenac sodium treatment altered reproductive metabolic status, androgenic activities and histo-architecture of the testis of male rats and induced hepatotoxicity and renal toxicity.     

Quercetin attenuates lambda cyhalothrin‐induced reproductive toxicity in male rats

The aim of this study was to evaluate the possible protective effects of Quercetin (Qe) against oxidative stress induced by λ cyhalothrin (LTC) in reproductive system. Thirty‐two male rats were divided into four groups. First group was allocated as the control group. Second group was given a Qe alone while the third group received a LTC alone. Animals in the fourth group were given a Qe with LTC. Caudae epididymis was removed for sperm analysis. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione‐S‐transferase (GST), and reduced glutathione (GSH) were determined in the testis. Additionally, the different histopathologic changes were observed in the testis of animals. LTC exposure significantly increased the abnormal morphology and LPO. On the contrary, sperm motility, viability and count, levels of GSH, and activities of SOD, CAT, GPx, and GST were significantly decreased compared to controls. Qe with LTC offset the decrease in functional sperm parameters, antioxidants enzymatic activities, and nonenzymatic antioxidant levels when compared with LTC‐treated rats. Furthermore, LTC showed irregular seminiferous tubules containing only Sertoli cells and Qe with LTC caused regular seminiferous tubules showing spermatogenesis at level of spermatocytes. We conclude that LTC‐induced oxidative stress and functional sperm parameters in male rats, and dietary of Qe attenuates the reproductive toxicity of LTC to restore the antioxidant system and sperm parameters in male rats. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 673–680, 2013.     

The influence of simultaneous exposure to carbon disulfide and hydrogen sulfide on the peripheral nerve toxicity and metabolism of carbon disulfide in rats

Three groups of 10 male Sprague-Dawley rats were exposed daily, 5 days a week for 25 weeks, either to 500 ppm carbon disulfide (CS2), 50 ppm hydrogen sulfide (H2S), or to both of them as a mixture and were periodically examined for sensory and motor tail nerve conduction velocity (SNCV, MNCV). A concomitant control group of 10 rats was used. In addition, rats exposed to 500 ppm CS2, and those simultaneously exposed to 500 ppm CS2 and 50 ppm H2S, were twice examined for 24-h urine excretion of 2-thio-thiazolidine-4-carboxylic acid (TTCA) in the course of the experimental period. Simultaneous exposure to CS2 and H2S had no significant interactive effect on nerve conduction velocities. A significant time-dependent slowing down of MNCV and SNCV occurred as the result of chronic exposure to CS2, including exposure to 500 ppm CS2 and to the mixture of 500 ppm CS2 and 50 ppm H2S, but did not occur after chronic exposure to 50 ppm H2S. With combined exposure to 500 ppm CS2 and 50 ppm H2S, the quantity of TTCA excreted in 24-h urine was not significantly different from that occurring in response to CS2 exposure alone. On the basis of these results it is suggested that chronic exposure to H2S would neither influence CS2-induced peripheral nerve toxicity nor obscure the interpretation of the measurement of urinary TTCA as a biological indicator of CS2 exposure.     

地塞米松的诱导效应对环磷酰胺大鼠毒性的影响

目的:观察地塞米松(dexamethasone,DEx)对大鼠细胞色素P450的诱导效应致环磷酰胺(cyclophos-phamide,CPA)对肝脏、肾脏、骨髓和膀胱毒性的影响.方法:雄性Wistar大鼠用DEX 50mg·kg-1·d-1诱导4d后,d5分别ip CPA 0,150和200mg·kg-1后36h,观察实验动物肝脏、肾脏、骨髓和膀胱毒性表现.结果:单独DEX诱导具有轻微的肝脏毒性.CPA单次给药造成骨髓细胞G2M期细胞的比例稍有升高,出现明显的尿蛋白和尿潜血.DEX的诱导作用增加了CPA的毒性:对肝毒性的增强作用主要表现在血浆ALT升高,肝脏总巯基和蛋白巯基含量降低,肝脏组织肝窦狭窄,肝小叶空泡变性;对肾脏毒性增强表现在血浆BUN和Cr升高,尿液蛋白和潜血增加,肾近端小管变性和髓质出血.DEX和CPA 200mg·kg-1合并用药组骨髓细胞的G0/G1期细胞增多,S期细胞明显减少.病理检查表明DEX和CPA合并用药组膀胱发生炎症和出血.结论:DEX诱导后使CPA对大鼠的肾脏、膀胱和骨髓毒性进一步增强,而DEX具有一定的肝脏毒性,与CPA合并给药后肝毒性有增强趋势.