trans-resveratrol relaxes the corpus cavernosum ex vivo and enhances testosterone levels and sperm quality in vivo

We examined the effects of trans-resveratrol on male reproductive functions; ex-vivo penile erection and in-vivo sperm counts and quality. For the ex-vivo study, the relaxation effects of resveratrol on isolated New Zealand white rabbit corpus cavernosum, precontracted by phenylephrine (5×10⁻⁵ M) were measured. The in-vivo study measured reproductive organ weights, blood testosterone levels, testicular histopathology, sperm counts, as well as the epididymal sperm motility and deformity of male ICR mice given an oral dose of resveratrol (50 mg/kg) for 28 days. Resveratrol elicited a concentration-dependent relaxing effect on corpus cavernosum, leading to a median effective concentration (EC₅₀) of 0.29 mg/mL. Repeated treatment with resveratrol (50 mg/kg) did not cause an increase in body weight, reproductive organ weight or testicular microscopic findings; however, resveratrol did elicit an increase in blood testosterone concentration, testicular sperm counts and epididymal sperm motility by 51.6%, 15.8% and 23.3%, respectively, without influence on sperm deformity. In conclusion, we propose that resveratrol has a positive effect on male reproductive function by triggering a penile erection, as well as enhancing blood testosterone levels, testicular sperm counts, and epididymal sperm motility.     

Bupropion treatment increases epididymal contractility and impairs sperm quality with no effects on the epididymal sperm transit time of male rats

Bupropion is a dopamine (DA) and norepinephrine (NE) reuptake inhibitor used as smoking cessation and antidepressant drug with a lower incidence of male sexual dysfunction. We showed previously that sibutramine, a norepinephrine/serotonine reuptake inhibitor, reduced male rat fertility. As there are no studies evaluating the impact of bupropion treatment on spermatic parameters and male fertility, we evaluated the effects of bupropion treatment (15 and 30 mg kg^?1, 30 days) on sexual behavior, spermatic parameters and fertility of male Wistar rats and on the epididymal duct in vitro contractility. Bupropion 15 mg kg^?1 increased the serum luteinizing hormone level and the epididymal duct contractility, but the sperm quality was not affected. At 30 mg kg^?1 bupropion impaired sperm quality increasing the incidence of non‐progressive sperm. The male sexual behavior and fertility were not modified at both bupropion doses. These results, in rats, suggest the importance of studies evaluating the effects of bupropion on the human male sperm quality. Copyright © 2015 John Wiley & Sons, Ltd.     

Bromochloroacetic acid exerts qualitative effects on rat sperm: implications for a novel biomarker.

Disubstituted haloacid by-products of drinking water disinfection such as dibromoacetic acid and dichloroacetic acid have been shown to perturb spermatogenesis and fertility in adult male rats. In the present study we sought to establish whether equimolar exposure to bromochloroacetic acid (BCA), a prevalent by-product in finished drinking water, is also capable of disrupting these endpoints, and if so to determine whether the novel biomarker of fertility (SP22) would be correlated with subfertility induced by testicular toxicity. A dose range finding study indicated that body weight was not affected by exposure to 14 daily doses of 72 mg/kg BCA while numerous male reproductive parameters were altered, including decreases in the number and progressive motility of cauda epididymal sperm. In addition, there was an increased incidence of delayed spermiation in the testes of males exposed to 72 mg/kg BCA. In the definitive study, exposures ranged from 8 to 72 mg/kg, the fertility of cauda epididymal sperm was evaluated by in utero insemination, and the two-dimensional profile of cauda sperm membrane proteins was evaluated quantitatively. The morphology of both caput and cauda epididymal sperm was altered by 72 mg/kg BCA. The fertility of cauda epididymal sperm, the percentages of progressively motile sperm and progressive tracks, and two sperm membrane proteins (SP22 and SP9) were decreased significantly by each BCA exposure. While the two sperm proteins and the two measures of progressive motility were each significantly correlated with fertility, only one of these measures (i.e., SP22) had an r value of greater than 0.5. When data for SP22 and fertility were fit to a nonlinear model, r(2) was 0.84. Using this exposure paradigm, the no-observed-effect level for BCA is less than 8 mg/kg. Moreover, SP22 may be useful in predicting compromised fertility after exposure to by-products of drinking water disinfection.     

A mixture of extracts from Peruvian plants (black maca and yacon) improves sperm count and reduced glycemia in mice with streptozotocin-induced diabetes

Abstract

We investigated the effect of two extracts from Peruvian plants given alone or in a mixture on sperm count and glycemia in streptozotocin-diabetic mice. Normal or diabetic mice were divided in groups receiving vehicle, black maca (Lepidium meyenii), yacon (Smallanthus sonchifolius) or three mixtures of extracts black maca/yacon (90/10, 50/50 and 10/90%). Normal or diabetic mice were treated for 7?d with each extract, mixture or vehicle. Glycemia, daily sperm production (DSP), epididymal and vas deferens sperm counts in mice and polyphenol content, and antioxidant activity in each extract were assessed. Black maca (BM), yacon and the mixture of extracts reduced glucose levels in diabetic mice. Non-diabetic mice treated with BM and yacon showed higher DSP than those treated with vehicle (p?<?0.05). Diabetic mice treated with BM, yacon and the mixture maca/yacon increased DSP, and sperm count in vas deferens and epididymis with respect to non-diabetic and diabetic mice treated with vehicle (p?<?0.05). Yacon has 3.05 times higher polyphenol content than in maca, and this was associated with higher antioxidant activity. The combination of two extracts improved glycemic levels and male reproductive function in diabetic mice. Streptozotocin increased 1.43 times the liver weight that was reversed with the assessed plants extracts. In summary, streptozotocin-induced diabetes resulted in reduction in sperm counts and liver damage. These effects could be reduced with BM, yacon and the BM+yacon mixture.     

Evaluation of effects of repeated sevoflurane exposure on rat testicular tissue and reproductive hormones

Abstract

Context: Evaluation of inhalation anesthetics on sperm and reproductive hormones are extremely important.

Objective: Investigation of the effects of sevoflurane used as an inhalation anesthetic on sperm morphology and reproductive hormones in rat testes.

Materials and methods: Forty Wistar-Albino male rats were divided into five groups of eight rats each. The control group received 2?L/min oxygen for seven days, 2?h/day while sevoflurane treatment S1 received 1 minimal alveolar concentration (MAC) sevoflurane?+?2?L/min oxygen for seven days, 2?h/day, and sevoflurane S2 received 1 MAC sevoflurane?+?2?L/min oxygen for seven days, 2?h/day followed by seven days of no treatment. Sevoflurane treatment S3 received 1 MAC sevoflurane?+?2?L/min oxygen for 14 days, 2?h/day and sevoflurane treatment S4 received 1 MAC sevoflurane?+?2?L/min oxygen for 14 days, 2?h/day, with no treatment for the following seven days. All rats were examined histologically after experimental procedures. Rat luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and inhibin levels were measured.

Results: Histological injury scores were significantly higher in S2, S3, and S4 receiving sevoflurane in comparison to the control group (p?=?0.001, <0.001, and 0.001, respectively). Sperm motility and concentration decreased in S3 and S4 compared to the control group (p?=?0.03 and 0.02, respectively). Significant differences were detected among all groups for serum LH, FSH, T, and inhibin serum concentrations (p?<?0.05).

Conclusion: Testicular and sperm morphology, and reproductive hormones were affected by chronic exposure to sevoflurane. However, more randomized, controlled, and well-designed clinical studies with larger population are needed to confirm of these results.     

The effect of aqueous extract of Rosa damascena on formaldehyde-induced toxicity in mice testes

Context: Rosa damascena L. (Rosaceae) (RD) essential oil and extracts are commonly used as a flavour in herbal medicine which increase libido. Previous studies have shown inhalation of RD flower’s oil increases libido and causes protective effects in formaldehyde (FA)-induced testicular damage.

Objective: The protective effects of aqueous extract of RD on the male reproductive system of mice were examined following FA-induced damage.

Materials and methods: Forty-eight adult NMRI male mice were randomly assigned to six groups (n?=?8): control (normal saline, 10?mg/kg); RD40 (40?mg/kg, p.o.); FA treated (10?mg/kg of 10%, i.p.) and FA?+?RD treated at 10, 20 and 40?mg/kg (FA?+?RD10), (FA?+?RD20) and (FA?+?RD40), respectively, for 40 days. At the end of treatment regimes, serum testosterone (T) level and the reproductive activity, viz. body/organ weights, testicular structure and sperm characteristics were studied.

Results: Formaldehyde administration significantly decreased serum T level (p?p?p?Discussion and conclusions: We may conclude that RD flower extract can withstand effects of FA in the male reproductive system of mice possibly due to its antioxidative properties.     

Male contraceptive efficacy of poly herbal formulation,contracept-TM,composed of aqueous extracts of Terminalia chebula fruit and Musa balbisiana seed in rat

Context: Terminalia chebula Retz (Combretaceae) and Musa balbisiana Colla (Musaceae) have a traditional reputation as a male contraceptive.

Objective: To determine the hypo-testicular activity of aqueous extracts of Terminalia chebula (fruit) and Musa balbisiana (seed) separately, and in composite manner at the ratio of 1:1 named as ‘Contracept-TM’ compared to cyproterone acetate (CPA), for developing a polyherbal contraceptive.

Materials and methods: The separate extract of above said plants or ‘Contracept-TM’ at the dose of 40?mg/100?g body weight of rat/day or CPA at 2?mg/100?g body weight of rat/day was administered for 28 days. Spermiological, androgenic and oxidative stress sensors, LD₅₀ and ED₅₀/100?g body weight values were measured.

Results: Treatment of individual, ‘Contracept-TM’ or CPA resulted significant decrease in the count of spermatogonia A (36.36–49.09%), pre-leptotene spermatocyte (19.11–55.30%), mid-pachytene spermatocyte (28.65–47.28%) and step 7 spermatid (29.65–51.59%). Activities of testicular Δ⁵, 3β (21.25–48.02%),17β-hydroxysteroid dehydrogenases (29.75–55.08%), catalase (19.06–43.29%) and peroxidase (30.76–62.82%), levels of testosterone (28.15–63.44%), testicular cholesterol (19.61–49.33%), conjugated diene (29.69–84.99%) and thiobarbituric acid reactive substances (41.25–86.73%) were elevated compare to the control. The ED₅₀ and LD₅₀ values were 40?mg and 5.8?g (T. chebula), 48?mg and 6.3?g (M. bulbisiana), 40?mg and 6.0?g (‘Contracept-TM’), respectively.

Discussion and conclusion: The said spermiological and androgenic sensors’ levels were decreased significantly by ‘Contracept-TM’ than its constitutional individual plant extract and it may be comparable to standard anti-testicular drug like CPA. So, it may be concluded that above polyherbal formulation is potent for inducing hypo-testicular activity.     

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.     

The effect of methoxychlor on the epididymal antioxidant system of adult rats

Methoxychlor is widely used as a pesticide in many countries and has been shown to induce reproductive abnormalities in male rats, causing reduced fertility. The mechanism of action of methoxychlor on the male reproductive system is not clear. In the present study we investigated whether administration of methoxychlor induces oxidative stress in the epididymis and epididymal sperm of adult rats. Methoxychlor (50, 100, or 200 mg/kg body weight/day) was administered orally for 1, 4, or 7 days. The animals were killed using anesthetic ether 24 h after of the last treatment. Epididymal sperm were collected by cutting the epididymis into small pieces in Ham's F-12 medium at 35 degrees C. The body weight and weights of the testis, liver, and kidney did not show any significant changes in the methoxychlor-treated rats. The weight of the epididymis, seminal vesicles, and ventral prostate as well as epididymal sperm counts decreased after 50, 100, or 200 mg/kg/day for 7 days but remained unchanged after shorter courses of treatment. Epididymal sperm motility was decreased in a dose-dependent manner in the animals treated with methoxychlor for 4 or 7 days. The activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase were decreased while the levels of hydrogen peroxide and lipid peroxidation were increased in the epididymal sperm as well as in the caput, corpus, and cauda epididymis after 4 or 7 days of treatment. The activities of superoxide dismutase decreased while the levels of lipid peroxidation increased in the liver but not in the kidney in all groups. Co-administration of the antioxidant vitamin E (20 mg/kg body weight/ day) to the 200 mg/kg/d methoxychlor-treated rats for 7 days prevented significant changes in the antioxidant systems in the epididymis and epididymal sperm and prevented alterations in sperm counts and motility. The results indicated that methoxychlor induces oxidative stress in the epididymis and epididymal sperm by decreasing antioxidant enzymes, possibly by inducing reactive oxygen species. In conclusion the adverse effect of methoxychlor on the male reproduction could be due to induction of oxidative stress.     

The effect of ornidazole on fertility and epididymal sperm function in rats

A comprehensive study of male fertility and sperm production and function was performed in 20 control and 20 rats treated with ornidazole, a compound with trichomonacidal activity. Rats were treated for 4 weeks at dosages of 0 (control) and 400 mg/kg/day of ornidazole during which fertility was assessed by weekly matings. Testicular sperm production and epididymal sperm function were assessed in one-half of the rats while the reversibility of effects after a 2-week recovery period was assessed in the remaining half. Male rats treated with ornidazole were infertile during the second week of treatment. After 4 weeks of treatment, testicular and epididymal weights, testicular spermatid counts, epididymal sperm reserves, sperm morphology, and sperm viability were similar in treated and control rats. A quantitative assessment of epididymal sperm motility using a dark-field photomicroscope with a stroboscopic light source revealed that ornidazole markedly inhibited sperm motility. Although the percentage of nonmotile sperm was not substantially increased in treated rats, the vigor of tail movement was markedly decreased which resulted in decreased sperm velocity. Restoration of fertility and normal sperm motility and velocity were observed in the group of recovery rats assessed 2 weeks after the cessation of ornidazole treatment. It is concluded that ornidazole, at a high dosage of 400 mg/kg/day, produces infertility in male rats by inhibiting epididymal sperm motility in terms of decreased sperm velocity. These effects are rapidly reversible after the cessation of treatment.     

Increased sensitivity to testicular toxicity of transplacental benzo[a]pyrene exposure in male glutamate cysteine ligase modifier subunit knockout (Gclm-/-) mice

Polycyclic aromatic hydrocarbons (PAHs), like benzo[a]pyrene (BaP), are ubiquitous environmental pollutants formed by the incomplete combustion of organic materials. The tripeptide glutathione (GSH) is a major antioxidant and is important in detoxification of PAH metabolites. Mice null for the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH concentrations. We investigated the effects of Gclm deletion alone on male fertility and spermatogenesis and its effect on the sensitivity of male embryos to the transplacental testicular toxicity of BaP. Gclm-/- males had dramatically decreased testicular and epididymal GCL enzymatic activity and total GSH concentrations compared with Gclm+/+ littermates. Ratios of reduced to oxidized GSH were significantly increased in Gclm-/- testes. GSH reductase enzymatic activity was increased in Gclm-/- epididymides. We observed no changes in fertility, testicular weights, testicular sperm head counts, or testicular histology and subtle changes in cauda epididymal sperm counts, motility, and morphology in Gclm-/- compared with Gclm+/+ males. Prenatal exposure to BaP from gestational day 7 to 16 was dose dependently associated with significantly decreased testicular and epididymal weights, testicular and epididymal sperm counts, and with vacuolated seminiferous tubules at 10 weeks of age. Gclm-/- males exposed prenatally to BaP had greater decreases in testicular weights, testicular sperm head counts, epididymal sperm counts, and epididymal sperm motility than Gclm+/+ littermates. These results show no effects of Gclm deletion alone on male fertility and testicular spermatogenesis and subtle epididymal effects but support increased sensitivity of Gclm-/- males to the transplacental testicular toxicity of BaP.     

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。     

Testicular and spermatotoxic effects of quinalphos in rats

Testicular and spermatotoxic effects were investigated in rats exposed to technical-grade quinalphos (70%) at dose levels of 0.52 mg kg(-1) (1/50th ld(50)) or 1.04 mg kg(-1) body weight (1/25th ld(50)) for 5 days a week for 60 days. The activities of marker testicular enzymes such as sorbitol dehydrogenase (SDH) and acid phosphatase were significantly decreased but those of lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and beta-glucuronidase were significantly increased in a dose-dependent manner. This particular pattern in the activity of testicular-cell-specific enzymes, a decrease in sperm motility and total epididymal sperm count and an increase in abnormal sperm suggest damage to germ cells and Sertoli cells. The testicular and spermatotoxic effects observed in rats may be due to the pesticide quinalphos or its metabolites.     

Reproductive toxicity of sodium valproate in male rats

Objectives:

To assess the effects of sodium valproate on rat sperm morphology, sperm count, motility, and histopathological changes in testis.

Materials and Methods:

Male Wistar rats (12 week old) were treated with sodium valpraote and sacrificed at the end of 2^nd, 4^th, 5^th, 7^th, 10^th and 15^th week after the last exposure to sodium valproate. Epididymal sperm count, sperm motility, sperm morphology, and histopathology of testes were analyzed.

Results:

Sperm count and sperm motility were decreased significantly by sodium valproate. The percentage of abnormal sperms increased in a dose-dependent manner. A histopathological study revealed that sodium valproate had caused sloughing of epithelial cells in testes.

Conclusion:

Sodium valproate causes reversible change in sperm motility, sperm count, morphology, and cytoarchitecture of testes.     

Effect of Metronidazole on Fertility and Testicular Function in Male Rats

Effect of Metronidazole on Fertility and Testicular Functionin Male Rats. MCCLAIN. R. M., DOWNING, J. C., AND EDGCOMB, J.E. (1989). Fundam. Appl. Toxicol 12,386–396. The reproductivetoxicology of metronidazole was studied in rats. Male CharlesRiver Crl:CD(SD)BR rats (10/group) were treated with metronidazoleas a dietary admixture at doses of 0 (control), 25, 100, and400 mg/kg/day for 8 weeks. The reversibility of effects aftera 3?-month recovery period was determined in separate groupsof 10 control and 10 rats treated with 400 mg/kg/day of metronidazole.After 2 and 4 weeks of metronidazole treatment, mating performanceand fertility in treated and control animals were comparable.After 6 weeks of treatment, all high-dose rats were infertile;however, fertility in low- and middose rats was not affected.High-dose male rats killed after 8 weeks of treatment showedmarkedly decreased testicular and epididymal weights, and markedlydecreased testicular spermatid counts and epididymal sperm counts.Most of the few epididymal sperm present in high-dose rats wereviable, but morphologically abnormal. Histologically, severedegeneration of the seminiferous epithelium was observed inthe testes of high-dose rats; the tubules were generally devoidof primary or secondary spermatocytes and spermatids. Rats treatedwith the low and middle doses of metronidazole exhibited normaltesticular and epididymal weights, and normal testicular spermatidcounts and epididymal sperm reserves. Epididymal sperm viabilityand morphology of treated and control animals were comparable.Minimal histologic changes were observed in the testes of middoserats, including degenerative fragmentation of spermatozoa andspermatids. In high-dose recovery rats, fertility was restoredin most rats by 8 weeks after the cessation of treatment; however,the testicular and epididymal weights and sperm counts of ratskilled after 3? months of recovery had increased but were stillsignificantly decreased in treated rats as compared with controls.Histologically, spermatogenesis was observed in most tubules;however, a portion of atrophic tubules persisted. It is concludedthat high doses of metronidazole produce infertility in themale rat through inhibition of spermatogenesis as early as thestage of the primary spermatocyte. This effect is partiallyreversible.     

Curcumin inhibits hyperlipidemia and hepatic fat accumulation in high-fructose-fed male Wistar rats

Context: Curcumin, an active principal of Curcuma longa Linn. (Zingiberaceae), has potent antioxidant and anti-inflammatory properties.

Objectives: This study investigated the effects of curcumin on hyperlipidemia and hepatic steatosis in high-fructose-fed Wistar rats.

Materials and methods: Forty male Wistar rats were divided into four groups with 10 rats in each. Two groups were fed with standard rodent diet and the other two with 60% high-fructose diet for 10 weeks. Curcumin (200?mg/kg body weight) was administered along with the diets simultaneously to each of the aforementioned diet groups. After 10 weeks of experiment, blood samples were collected from tail vein. Liver, adipose and epididymal tissues were collected after sacrifice of the animals and stored for further analyses.

Results: Administration of curcumin reduced body weight (280.6?±?7.4?g), liver weight (2.5?±?0.2?g/100?g BW), adipose weight (1.4?±?0.3?g/100?g BW), plasma levels of TAG (86.1?±?13.5?mg/dL), VLDL-C (17.2?±?2.7?mg/dL), lipid ratios and increased HDL-C (28.4?±?4.5?mg/dL) in fructose-fed rats. Curcumin supplementation significantly lowered TAG content and decreased the protein expression of LXR-α (43%) and SREBP1c (59%) in the liver. Furthermore, curcumin suppressed the expression of lipogenic enzymes, ACLY (95%), ACC (50%) and FAS (77%) in rats fed with high-fructose diet. No significant change was found in the expression of PPAR-α.

Discussion and conclusion: Curcumin prevented the high-fructose induced hyperlipidemia and hepatic steatosis.     

Immunomodulatory activity of Buchholzia coriacea seed methanol extract on Trypanosoma brucei brucei infected mice

Context: The seeds of Buchholzia coriacea Engler (Capparaceae) are used in Eastern Nigeria to treat feverish conditions, and to treat malaria and sleeping sickness that cause fever.

Objective: The current study assesses the immunomodulatory activity of Buchholzia coriacea seed extract on Trypanosoma brucei brucei infected mice.

Materials and methods: Delayed hypersensitivity reaction, humoral antibody response and in-vivo leucocyte mobilization tests were assessed in three different experiments to determine the effect of the extract on immune response. Seventy-five (75) mice (25 mice per experiment) were used for the study and were each infected with 1.00?×?10⁶ trypanosomes intra-peritoneally. Groups A, B and C were given 250, 500 and 1000?mg/kg of the extract, respectively, group D received 7.5?mg/kg body weight of levamisole and group E was the control. Sheep RBCs were used as antigen.

Results: The acute toxicity tests did not cause clinical signs or death within 24?h post treatment at all the doses tested. The extract inhibited delayed hypersensitivity reaction by 20.9 and 20.8% at 250 and 500?mg/kg, respectively, while at 1000?mg/kg, the paw size increased (?101.9%) when compared with the control. The extract elevated the antibody titre from 1.60?±?0.40 for control to 8.00?±?3.58 for 500?mg/kg group. The extract increased in total leucocytes counts.

Discussion and conclusion: The extract has a very wide safety margin and was able to improve immune response. The results of the present study showed that Buchholzia coriacea seed methanol extract possesses immunostimulatory activity on trypanosome-infected mice.     

Protective effects of grape seed procyanidin extract against nickel sulfate-induced apoptosis and oxidative stress in rat testes

This study determined whether nickel sulfate (Ni)-induced reproductive damage occurs via apoptosis and oxidative stress and to examine the expression of Bax and c-kit and their effects on Ni exposure. The study also explored the protective effects of grape seed proanthocyanidin extract (GSPE) against Ni toxicity in the testes. Wistar rats were treated with normal saline, Ni alone (1.25, 2.5, and 5?mg/kg/day), and Ni (2.5?mg/kg/day) plus GSPE (50 and 100?mg/kg/day). After 30 days, Ni significantly decreased sperm motility and the percentage of S-phase cells and enhanced testicular apoptosis in the 2.5 and 5?mg groups. The levels of malondialdehyde (MDA), hydrogen peroxide (H₂O₂), and nitric oxide (NO) significantly increased. The decreased activity of glutathione peroxidase and catalase in the Ni groups showed that Ni could increase oxidative stress, especially at 2.5 and 5?mg. Western blot analysis showed that the expression of Bax protein and c-kit increased in 2.5 and 5?mg Ni groups compared with controls. Conversely, these changes were partially attenuated in rats simultaneously administered GSPE, especially in the 100?mg group. These results demonstrate the following: (1) Ni exhibits reproductive toxicity in rats by decreasing sperm at concentrations of 2.5 and 5?mg; (2) intratesticular apoptosis, oxidative stress, and c-kit overexpression play pivotal roles in reproductive damage induced by Ni; and (3) GSPE enhances sperm motility by down-regulating c-kit expression and offsetting the apoptosis and oxidative stress induced by Ni by directly decreasing MDA and NO, scavenging H₂O₂, and down-regulating Bax expression.     

蒽贝素对雄性大鼠血浆性激素水平及附睾精子质量的影响

目的 研究蒽贝素对雄性大鼠血浆性腺激素水平、附睾精子质量、睾丸组织结构的影响,探讨蒽贝素降低雄性大鼠生育能力的作用机制。方法 给雄性性成熟大鼠sc蒽贝素铵盐溶液30 d,末次给药后2 h,测定血浆性激素水平;检查附睾精子质量;观察睾丸组织结构。结果 与对照组比较,给药30 d后,蒽贝素高、中剂量（40、20 mg/kg）组大鼠血浆睾酮、黄体生成素、卵泡刺激素水平、附睾精子活率、精子密度明显降低,组间差异有统计学意义（P＜0.05）,附睾精子畸形率和顶体完整率无明显变化,显微镜下见睾丸组织呈萎缩性病变,曲精细管扁平、塌陷,管内精母细胞减少,附睾精细管内精子稀少。结论 蒽贝素抑制丘脑-垂体-性腺轴活动,降低雄性大鼠血浆性激素水平,引起睾丸萎缩和附睾精子活率、精子密度降低,使雄性大鼠生育能力下降。     

Thiazolidinediones: comparison of long-term effects on glycemic control and cardiovascular risk factors

SUMMARY

Objective: To compare the long-term effects on HbA_1c, lipid parameters, body weight, and hepatotoxicity after switching type 2 diabetes patients from troglitazone to either pioglitazone or rosiglitazone.

Methods: Of 125 study candidates from a previous prospective study, 100 patients (51 pioglitazone, 49 rosiglitazone) met criteria for comparing HbA_1c, lipids, body weight, and incidence of hepatotoxicity over 2 successive observation periods (3.1 and 12.6?months).

Results: Mean absolute HbA_1c decreased significantly, 0.53 and 0.27% in the pioglitazone and rosiglitazone groups, respectively, at the 12.6-month observation. Mean triglyceride (TG) decreased in the pioglitazone group at each interval with a cumulative decrease of 26.4% from baseline. In contrast, TG increased in the rosiglitazone patients by 43.3% at 3.1?months and then decreased (but remained above baseline) at 12.6?months. Mean high density lipoprotein (HDL) increased 22.1% with pioglitazone and 13.3% with rosiglitazone. In patients who had a baseline HDL < 35?mg/dL (0.91?mmol/L), pioglitazone-treated patients experienced a significant increase at each interval resulting in a 52.6% increase in HDL compared to a 26.9% increase for rosiglitazone patients. Patients in both treatment groups had similar weight increases at each interval and no hepatotoxicity was noted.

Conclusion: With pioglitazone or rosiglitazone, changes in glycemic control, lipid effects, and body weight appear to continue over time. Pioglitazone treatment resulted in decreased triglyceride levels, while rosiglitazone was associated with an increase in triglyceride levels. HDL increased in both treatment groups, but in patients with a baseline HDL < 35?mg/dL (0.91?mmol/L), pioglitazone improved the HDL to a greater extent than rosiglitazone.