Testicular and spermatotoxic effect of nitrate in mice

A study was conducted with nitrate to assess the testicular and spermatotoxic effects in mice at doses to which human beings are exposed as well as at higher dose levels in the drinking water. Potassium nitrate was administered to mice at dose levels 90, 200, 500, 700 and 900 ppm for 35 days. There was no difference in the uptake of water in control and treated animals. The amount of nitrate intake/ mouse/day calculated on the basis of water intake in the different groups ranged from 22.5 to 27, 50 to 60, 125 to 150, 175 to 210 and 225 to 270 mg/kg body weight. No changes were evident in the body weight, testicular, epididymal and accessory organ weight at all the dose levels tested, although a decline in sperm count and sperm motility along with an increase in abnormal sperm was noticed at 900 ppm. The activity of marker testicular enzymes, mainly 17-beta hydroxysteroid dehydrogenase (17-betaHSD) and gamma glutamyl transpeptidase (gamma-GT), associated with specific cell types were altered. Histopathological changes including atrophy and disturbed spermatogenesis were observed only at the 900-ppm dose level. In conclusion, we can say that the testicular and spermatotoxic effects are observed only at the highest dose level, which is not likely to be encountered in the drinking water.     

Sublethal toxicity of quinalphos on oxidative stress and antioxidant responses in a freshwater fish Cyprinus carpio

Extensive use of quinalphos, an organophosphorus pesticide, is likely to reach the aquatic environment and thereby posing a health concern for aquatic organisms. Oxidative stress and antioxidant responses may be good indicators of pesticide contamination in aquatic organisms. The data on quinalphos induced oxidative stress and antioxidant responses in carps are scanty. This study is aimed to assess the two sublethal concentrations of quinalphos (1.09 and 2.18 μL L^?1) on oxidative stress and antioxidant responses of Cyprinus carpio for a period of 20 days. In liver, the malondialdehyde level was found to be significantly increased in both the concentrations. The results of the antioxidant parameters obtained show a significant increase in superoxide dismutase, catalase, and glutathione‐S‐transferase activity in liver of fish. These results demonstrate that environmentally relevant levels of the insecticide quinalphos can cause oxidative damage and increase the antioxidant scavenging capacity in C. carpio. This may reflect the potential role of these parameters as useful biomarkers for the assessment of pesticide contamination. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1399–1406, 2016.     

The antioxidant/anti-inflammatory protective effects of rutin against ethanol-induced testicular perturbation in rats: Involvement of the immunosuppressive indoleamine 2,3-dioxygenase

This study investigated the influence of rutin against EtOH-induced testicular impairment in rats and the involvement of the indole-aminergic pathway. Four groups of eight rats each were orally exposed to drinking water (Group 1), EtOH (5 g/kg bwt, Group 2), R (5 g/kg bwt, Group 3), and EtOH + R (5 g/kg bwt + 50 mg/kg bwt, Group 4) via gavage for 15 days. Results showed that exposure to EtOH significantly (p < 0.0001) reduced the testicular antioxidant system and increased lipid peroxidation (LPO) relative to control. We observed a significant (p < 0.0001) increase in the inflammatory biomarkers, with attendant disruption in the testicular histological structure and concomitant elevation in the activities of indoleamine 2,3-dioxygenase (IDO), in comparison with control and no noticeable effects in tryptophan 2,3-dioxygenase (TDO) activity across the groups. Rutin-only exposed group did not show any alteration in the measured parameters when compared with the control. Rutin co-exposure augmented the antioxidant system, prevented histological damage, reduced LPO and inflammation, and thus, lowered EtOH-mediated increase in IDO activity, compared with control. Overall, these findings reveal the involvement of the indole-aminergic pathway in rutin's protective influence against EtOH-induced testicular impairment in rats.     

Lack of spermatotoxic effects of methyl and ethyl esters of p-hydroxybenzoic acid in rats.

Parabens are alkyl esters of p-hydroxybenzoic acid widely used as preservatives in foodstuffs, cosmetics toiletries and pharmaceuticals. These compounds are known to exert a weak estrogenic activity in estrogen receptor assays in vitro. In addition butyl and propyl parabens show uterotrophic activity in vivo. It was previously shown that exposure of post-weaning rats and mice to butyl or propyl parabens adversely affects the secretion of testosterone and the function of the male reproductive system. In the present study, it is shown that methyl and ethyl parabens do not adversely affect the secretion of sex hormones or the male reproductive function. Methyl and ethyl parabens were administered to 25-27-day-old rats assigned to five groups of eight animals each, at doses of 0.1% and 1.0% each in the rat's diet. At the end of 8 weeks, the rats were sacrificed by decapitation and the weights of the testes, epididymides, prostates, seminal vesicles and preputial glands were determined. There were no treatment-related effects of either compound on the organ weights in any of the study groups. Neither compound exhibited anti-spermatogenic effects nor elicited changes in levels of testosterone, LH and FSH at a dose level of about 1000 mg/kg of body weight per day.     

Cytogenetic effects of quinalphos in mice

The cytogenetic effect of quinalphos was studied in Swiss albino mice using the micronucleus test, bone marrow and germ cell chromosome assays and sperm morphology assay. Quinalphos at 5, 10 and 15 mg/kg body weight was administered orally to mice. Quinalphos induced micronuclei in the bone-marrow cells of mice and also caused a significant increase in chromosomal aberrations in bone-marrow cells (at 10 and 15 mg/kg body weight dose levels) and in germ cells (at all tested doses). A high incidence of abnormal sperms was also observed in mice treated with quinalphos.     

Toxicity of the quinalphos metabolite 2-hydroxyquinoxaline: growth inhibition, induction of oxidative stress, and genotoxicity in test organisms

The quinalphos metabolite 2-hydroxyquinoxaline (HQO), previously shown to photocatalytically destroy antioxidant vitamins and biogenic amines in vitro, was tested for toxicity in several small aquatic organisms and for mutagenicity in Salmonella typhimurium. In the rotifer Philodina acuticornis, HQO caused the disappearance of large individuals and increased hydroperoxide concentration. The latter effect was not only observed in animals kept in a light/dark cycle, but also in constant darkness, indicating that HQO can assume a reactive state and/or form reactive intermediates under the influence of either light or redox-active metabolites, in particular, free radicals. Cell proliferation was inhibited in the ciliate Paramecium bursaria. In the dinoflagellate Lingulodinium polyedrum, which allows early detection of cellular stress on the basis of bioluminescence measurements, strong rises in light emission became apparent on the 2nd day of exposure to HQO and continued until cells died between 12 and 18 days of treatment. Oxidative damage of protein by HQO was demonstrated by measuring protein carbonyl in L. polyedrumin vivo as well as in light-exposed bovine serum albumin in vitro. In an Ames test of mutagenicity, HQO proved to be genotoxic in both light- and dark-exposed bacteria. HQO appears as a source of secondary quinalphos toxicity, which deserves further attention.     

依立雄胺对大鼠、犬和人精子活力的影响

目的　用更敏感的指标评价依立雄胺的生殖毒性。方法　将精悬液与不同浓度的依立雄胺共育1h ,2h后 ,借助计算机辅助分析系统录像分析精子活力参数的变化。结果　大鼠精子给予终浓度为0 .6 ,6和 6 0 μmol·L- 1的依立雄胺 1h后 ,精子活率(MOT)较对照组分别下降 19.0 %,18.0 %,16 .0 %;2h后 ,中高剂量组的MOT较对照组分别下降9.0 %,10 .0 %,且高剂量组的前向性降低。Beagle犬给予终浓度 0 .6 ,6和 6 0 μmol·L- 1依立雄胺 1h后MOT较对照组呈下降趋势 ,但无显著性差异 ,2h后MOT较对照组分别下降 31.0 %,2 4 .9%,2 8.3%。人精子体外给药实验中 ,给予终浓度为0 .12 ,0 .2 4和 0 .96 μmol·L- 1的依立雄胺 2h后 ,曲线运动速度、直线运动速度较对照组呈下降趋势 ,但无显著性差异 ,而高剂量组的精子头侧摆幅度、精子尾摆动性及MOT较对照组分别下降 2 8.0 %,5 .0 %,15 .0 %。结论　依立雄胺对精子具有一定的直接毒性 ,这种毒性存在种属差异 ,且不表现为剂量 反应关系。     

萘普替尼对雄性大鼠睾丸形态结构和附睾精子质量的影响

目的 探究萘普替尼对雄性大鼠睾丸形态结构及附睾精子质量的影响。方法 将30只雄性SD大鼠随机分为30和70 d两组,每组又分为对照组和萘普替尼低、高剂量组（0.75、3.00 mg/kg）,ig给药,每天给药1次,给药体积10 mL/kg。每天进行1次症状观察,每周称量一次体质量,大鼠分别于给药35和70 d后次日处死,肉眼检查各脏器有无异常,检测双侧睾丸质量和横径、附睾尾精子数量和活力,睾丸固定进行组织病理学检查。结果 萘普替尼高剂量组动物均从给药第14天开始,出现腹泻、脱毛、口鼻眼处有红色分泌物,随着给药天数的增加,症状加重;给药70 d组其中1只动物于给药60 d开始出现血尿症状。给药35 d组大鼠从给药21 d开始,给药70 d组从14 d开始,高剂量大鼠体质量明显低于同期对照组（P<0.01）。与对照组比较,给药组雄鼠的双侧睾丸绝对质量和脏器指数、睾丸横径、附睾尾精子数量和活力及睾丸组织病理学检查并未随给药剂量的增加和给药时间的延长而出现明显变化。结论 萘普替尼对雄性大鼠的睾丸组织及精子质量无明显影响。     

Fetotoxic response of technical quinalphos in rats.

Technical Quinalphos was administered po to pregnant rats through day 6-20 of gestation at doses of 0.5 or 1.5 mg/kg body weight. Quinalphos produced enzymatic changes in liver and serum of dams associated with mild pathomorphological changes in liver and brain. Fetotoxic effects were not observed at the tested dose levels as determined by total number of implantations, percentage resorption, live fetuses, crown rump length and fetal weight. A few insignificant skeletal deformities were noticed. A significant inhibition of acetylcholinesterase activity in fetal brain and placenta indicated possible transmigration of quinalphos from dams to fetuses.     

Transient effect of single dose exposure of Nigerian Bonny-light crude oil on testicular steroidogenesis in Wistar rats is accompanied by oxidative stress

The folkloric use of Nigerian Bonny-light crude oil (BLCO) in Niger Delta area of Nigeria is a common practice. There is increasing experimental evidence portending the adverse effects of BLCO an environmental toxicant on testicular function. We investigated the effects of single dose of BLCO (800?mg/kg body weight) on the activities of steroidogenic and antioxidant enzymes such as serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone, 3 β-hydroxy-steroid dehydrogenase (3 β-HSD), 17 β-hydroxy-steroid dehydrogenase (17 β-HSD), superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione peroxidase (GSH-Px), levels of lipid peroxidation (LPO), glutathione reduced (GSH) and steroidogenic acute regulatory (StAR) protein, in testes of rats. There was a sequential reduction in the concentration of steroid hormones and activities of steroidogenic enzymes with a concomitant decrease in levels of StAR protein, followed by a parallel increase in antioxidant enzyme activities and levels of LPO. These findings revealed inhibitory effects of BLCO on testicular steroidogenesis and the possible role of oxidative stress in testicular dysfunction observed in this study.     

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.     

Comparison of the stimulus effects of ethylketocyclazocine in fischer and Sprague-Dawley rats

The discriminative stimulus effects of ethylketocyclazocine (EKC) were characterized in Fischer and Sprague-Dawley rats trained to discriminate 0.3 mg/kg of EKC (s. c.) from saline in a two-choice, discrete-trial avoidance paradigm. The putative mu-opioid receptor agonists morphine and fentanyl, as well as the putative kappa-opioid receptor agonists EKC and U50,488H generalized completely with the EKC cue in both strains of rats. Only small quantitative differences between strains were observed in the generalization of these agonists with EKC. However, Sprague-Dawley rats were notably more sensitive than Fischer rats to the depressant effects of fentanyl. Only small quantitative differences between strains were also observed in the dose of naloxone necessary for complete antagonism of the EKC-like stimulus effects of the mu- and kappa-opioid agonists. The mu-opioid agonists were approximately 2–6 times more sensitive to naloxone antagonism than the kappa-opioid agonists in both Fischer and Sprague-Dawley rats. However, due to inter-animal variability, this difference was not statistically significant. The results of this study suggest that one or more opioid receptor subtype(s) may be involved in the production of the EKC cue in both strains of rats.     

Lack of effects of nose-only inhalation exposure on testicular toxicity in male rats.

Reductions in testicular mass, sperm motility, and mating frequency have been attributed to the stresses caused by confinement of Sprague-Dawley male rats in nose-only inhalation exposure tubes. Testicular changes, including an increase in testicular atrophy, have been detected at an increased incidence in male rats used in inhalation studies as compared with rats of the same age and strain used in oral toxicity studies. This study was designed to determine whether nose-only exposure of male rats caused testicular toxicity under conditions of cooling of the exposure room and appropriate acclimation to the exposure tubes. In order to acclimate the rats to the nose-only inhalation exposure apparatus, all male rats were placed in the exposure tubes for at least four successively increasing time intervals (15, 30, 45, and 60 min) on 4 separate days, with a rest period of approximately 48 h between the first and second acclimation. Twenty male rats were exposed nose-only to filtered air for approximately 2 h per day for 28 days before cohabitation and continuing throughout a 14-day cohabitation period. To reduce thermal stress, the exposure room temperature was maintained at 64 to 70 degrees F. Twenty control rats were housed in the same room as the exposed rats but were not placed in exposure tubes. End points monitored were body weight, testicular weight, sperm count, sperm motility, and histopathology of the testes, epididymides, prostate, and seminal vesicles. The control rats gained weight more rapidly than the exposed rats. All the rats in both groups mated successfully, and testicular weights, normalized to body weight, were similar for both groups. More importantly, there were no microscopic changes that could be considered an adverse effect on the reproductive tissues in the male rats placed in exposure tubes. Thus, nose-only exposure for up to 2 h per day for a total of 42 days did not cause adverse effects on the reproductive organs, fertility, or reproductive performance of male rats under the conditions of this study.     

Hepatic and intestinal first-pass effects of oltipraz in rats

It was reported that the mean value of the extent of absolute oral bioavailability (F) of oltipraz at a dose of 20 mg/kg was 41.2% and only 2.68% of the oral dose was unabsorbed from the gastrointestinal tract in rats. Hence, the low F in rats could be due to considerable first-pass (gastric, intestinal and hepatic) effects. Hence, the first-pass effects of oltipraz were measured after intravenous, intraportal, intragastric and intraduodenal administration of the drug at a dose of 20 mg/kg to rats. The total area under the plasma concentration-time curve from time zero to time infinity (AUC) values between intragastric and intraduodenal administration (213 and 212 microg min/ml) in rats were almost similar, but the values were significantly smaller than that after intraportal administration (316 microg min/ml) in rats, indicating that gastric first-pass effect was almost negligible (due to negligible absorption of oltipraz from rat stomach), but the intestinal first-pass effect of oltipraz was considerable, approximately 32% of the oral dose. The hepatic first-pass effect of oltipraz was approximately 40% based on AUC values between intravenous and intraportal administration (319 versus 536 microg min/ml). Since approximately 65% of the oral oltipraz was absorbed into the portal vein, the value of 40% was equivalent to 25% of the oral dose. The low F of oltipraz in rats was mainly due to considerable hepatic and intestinal first-pass effects.     

Comparative studies on the spermatotoxic effects of dinoseb and its structurally related chemicals

Three dinitrophenolic compounds, dinoseb (DNBP; 7.5 mg/kg b.w.), 4,6-dinitro-o-cresol (DNOC; 4, 7.5, 15 mg/kg b.w.), and 2,4-dinitrophenol (DNP; 7.5, 15, 30 mg/kg b.w.) were administered orally to sexually matured Jcl:SD male rats for 5 consecutive days. Half of the males in each group were necropsied at 3 (D3) and 14 (D14) days after the last dosing, respectively, and examined for the effects of dinitrophenols on spermato-/spermiogenesis. DNBP (7.5 mg/kg), DNOC (15 mg/kg), and DNP (30 mg/kg) caused 1, 5, and 0 deaths, respectively, as well as a decreased body weights during the treatment. Although examinations on D3 revealed no treatment-related alterations, DNBP and DNOC resulted in reduced sperm motility and increased incidence of tailless sperm in the cauda epididymis on D14. DNP also caused slightly increased incidence of tailless sperm on D14. These results demonstrate that DNBP, DNOC, and DNP manifest similar spermatotoxic effects at or around a lethal dose in rats.     

Testicular effects of monensin,a golgi interfering agent in male rats

Abstract

Objective: The present study was undertaken to explore the effects of monensin, a potent Golgi disturbing agent on male fertility. Methods: Male Wistar rats were administered monensin at the dose levels of 2.5, 5, and 10?mg/kg b wt. Animals were sacrificed after 67 days of the treatment. The activities of lactate dehydrogenase (LDH), ATPase, acid phosphatase and thiamine pyrophosphatase (TPPase) were measured in the testis. Cytochemical assay of Golgi body marker enzyme, thiamine pyrophosphatase was also performed. Ultrastructural changes in testis were studied by Transmission electron microscopy. Sperm number and motility were also examined. Results and discussion: The alterations in the activities of above mentioned enzymes indicate the pronounced effect of the drug on the functioning of spermatogenic cells. The findings from electron microscopy such as membrane disruption, swelling and disintegration of Golgi apparatus strongly suggest the interference of monensin with the functioning of Golgi apparatus in the spermatogenic cells. Data from the sperm number and motility as well as the fertility studies and the resulted litter size further points towards the antifertility effects of monensin in male rats. Conclusion: The findings from the present study strongly indicated the effects of monensin on the testis, involving alterations in key enzyme activities and changes at the ultrastructural level.     

Investigation of Turnera ulmifolia effects in pregnant rats and offspring

Turnera ulmifolia Linn. (Turneraceae) is an herb commonly found in northeastern Brazil, frequently employed in folk medicine, including by pregnant woman, for many afflictions due to it expectorant, tonic, anti-inflammatory, antiulcerogenic, and antioxidant effects. This work studied the infusion commonly used by the population, obtained by maceration of fresh leaves of T. ulmifolia in filtered water, to evaluate if the same may promote alterations in rat gestation and exposed offspring. Pregnant rats received, by gavage, the aqueous extract (0, 1, 2, or 3 g/kg/day) from gestation day (GD) 1 to GD 21. The treatment was not able to promote maternal toxicity: body weight gain, food and water intake were not altered during gestation period. The offspring presented normal physical and reflexological development. No alterations were observed in the histopathological study and sexual hormone levels of the dams and offspring at 30, 60, and 90 days of age. The sexual behavior was evaluated in male and female offspring at adult age (GD 90) and no alterations were observed. These results suggest that the infusion of T. ulmifolia, employed in folk medicine, at these doses, is not able to promote alterations to pregnant rats, to impair gestation, or to damage the exposed offspring.     

Therapeutic and fertility restoration effects of Ionidium suffruticosum on sub-fertile male albino Wistar rats: effects on testis and caudal spermatozoa

Context: Ionidium suffruticosum (L.) Ging (Violaceae) is an important medicinal plant widely used as a herbal traditional medicine in Ayurveda for the treatment of infertility. Currently, little pharmacological information is available on its male fertility properties following prolonged use.

Objective: To investigate I. suffruticosum leaf extracts for male fertility parameters.

Materials and methods: The ethanol lyophilized fraction was administered orally on carbendazim-induced sub-fertility rats (250?mg/kg body weight for 28 days). The effects of fractions on rat’s fertility parameters i.e., body and testes weight, sperm motility, sperm vitality, epididymal sperm counts, its morphology, enzyme and antioxidant stress and histopathology were studied and compared with clomiphene citrate.

Results: The sub-fertile male rats treated with I. suffruticosum leaf extract increased the body weight of 7?g, testis weight of 97?mg, increased cauda epididymal sperm counts of 34.2?×?10⁶ sperm/mL, motility of sperm 46% and vitality 28% also increased and normal sperm morphology also improved up to 32%. The carbendazim-treated group showed loss in body weight of 33?g, testis weight of 851?mg, decreased epididymal sperm counts of 15?×?10⁶ sperm/mL, with sluggish motility and a highly significant fall in the live sperms of about 57%.

Discussion and conclusion: The leaf fraction of I. suffructicosum increased the testicular weight, spermatogenesis, sperm counts, lessened sperm agglutination, and increased testicular oxidative biomarkers, SOD, and CAT. This study therefore supports the usage of I. suffructicosum in traditional medicine for infertility.