ObjectiveTo study the protective effect of lipoic acid (LA) on the spermatogenic function of the male rats with oligoasthenozoospermia induced by ornidazole (ORN).

METHODSSeventy male SD rats were equally randomized into groups A (solvent control: 1 ml 0.5% CMC-Na + 1 ml olive oil), B (low-dose ORN model: 400 mg/kg ORN suspension + 1 ml olive oil), C (low-dose ORN + low-dose LA treatment: 400 mg/kg ORN + 50 mg/kg LA), D (low-dose ORN + high-dose LA treatment: 400 mg/kg ORN + 100 mg/kg LA), E (high-dose ORN model: 800 mg/kg ORN suspension + 1 ml olive oil), F (high-dose ORN + low-dose LA treatment: 800 mg/kg ORN + 50 mg/kg LA), and G (high-dose ORN + high-dose LA treatment: 800 mg/kg ORN + 100 mg/kg LA), and treated respectively for 20 successive days. Then all the rats were sacrificed and the weights of the body, testis, epididymis and seminal vesicle obtained, followed by calculation of the organ index, determination of epididymal sperm concentration and motility, and observation of the histomorphological changes in the testis and epididymis by HE staining.

RESULTSCompared with group A, group E showed significantly decreased body weight (［117.67 ± 11.53］ vs ［88.11 ± 12.65］ g, P < 0.01) and indexes of the testis (［1.06 ± 0.12］ vs ［0.65 ± 0.13］ %, P < 0.01) and epididymis (［0.21 ± 0.03］ vs ［0.17 ± 0.01］ %, P < 0.01). In comparison with group E, group F exhibited remarkable increases in the epididymal index (［0.17 ± 0.01］ vs ［0.20 ± 0.02］ %, P < 0.01), and so did group G in the body weight (［88.11 ± 12.65］ vs ［102.70 ± 16.10］ g, P < 0.05) and the indexes of the testis (［0.65 ± 0.13］ vs ［0.95 ± 0.06］ %, P < 0.01) and epididymis (［0.17 ± 0.01］ vs ［0.19 ± 0.02］ %, P < 0.05), but no obvious difference was observed in the index of seminal vesicle among different groups. Compared with group A, group B manifested significant decreases in sperm motility (［74.12 ± 8.73］ vs ［40.25 ± 6.08］ %, P < 0.01), and so did group E in sperm count (［38.59 ± 6.40］ vs ［18.67 ± 4.59］ ×105/100 mg, P < 0.01) and sperm motility (［74.12 ± 8.73］ vs ［27.58 ± 8.43］ %, P < 0.01). Sperm motility was significantly lower in group B than in C and D (［40.25 ± 6.08］ vs ［58.13 ± 7.62］ and ［76.04 ± 8.44］%, P < 0.01), and so were sperm count and motility in group E than in F and G (［18.67 ± 4.59］ vs ［25.63 ± 9.66］ and ［29.92 ± 4.15］ ×105/100 mg, P < 0.05 and P < 0.01; ［27.58 ± 8.43］ vs ［36.56 ± 11.08］ and ［45.05 ± 9.59］ %, P < 0.05 and P < 0.01). There were no obvious changes in the histomorphology of the testis and epididymis in groups A, B, C and D. Compared with group A, group E showed necrotic and exfoliated spermatogenic cells with unclear layers and disorderly arrangement in the seminiferous tubules and remarkably reduced sperm count with lots of noncellular components in the epididymal cavity, while groups F and G exhibited increased sperm count in the seminiferous tubules and epididymis lumen, also with exfoliation, unclear layers and disorderly arrangement of spermatogenic cells, but significantly better than in group E.

CONCLUSIONSLA can reduce ORN-induced damage to the spermatogenetic function of rats, improve sperm quality, and protect the reproductive system.

Animals ; Antioxidants ; pharmacology ; Asthenozoospermia ; chemically induced ; drug therapy ; Body Weight ; drug effects ; Epididymis ; anatomy & histology ; drug effects ; Male ; Oligospermia ; chemically induced ; drug therapy ; Ornidazole ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Seminal Vesicles ; anatomy & histology ; drug effects ; Seminiferous Tubules ; anatomy & histology ; drug effects ; Sperm Count ; Sperm Motility ; drug effects ; Spermatogenesis ; drug effects ; Spermatozoa ; drug effects ; Testis ; anatomy & histology ; drug effects ; Thioctic Acid ; pharmacology

Objective: To investigate the improving effect of astaxanthin (AST) on the sperm quality of rats with ornidazole (ORN)-induced oligoasthenozoospermiaand its action mechanism. METHODS: Forty adult male SD rats were equally randomized into groups A (solvent control), B (low-dose ORN ［400 mg/（kg·d）］), C (high-dose ORN ［800 mg/（kg·d）］), D (low-dose ORN ［400 mg/（kg·d）］ + AST ［20 mg/（kg·d）］), and E (high-dose ORN ［800 mg/（kg·d）］ + AST ［20 mg/（kg·d）］), all treated intragastrically for3 weeks.After treatment, the epididymal tails ononeside was taken for determination of sperm concentration and activity, and the epididymideson the other side harvested for measurement of the activities of GSH-Px, GR, CAT and SOD and the MDA contentin the homogenate. RESULTS: Compared with group A, sperm motilityin the epididymal tail andGSH-Px and SOD activities in theepididymiswere markedly decreased while the MDAcontent significantlyincreased in group B (P<0.05), spermmotility and concentrationin the epididymal tail, testisindex, and the activities of GSH-Px, GR, CAT and SOD in the epididymis were remarkably reduced while theMDA contentsignificantly increased in group C(P<0.05). In comparison with group B, group D showed markedly increased sperm motility (［45.3±8.7］% vs ［66.3±8.9］%, P<0.05) in the epididymal tail and SOD activity in the epididymis (［116.7±25.3］ U/mg prot vs ［146.1±23.8］ U/mg prot, P<0.05), decreased MDA content(［1.68±0.45］ nmol/mg prot vs ［1.19±0.42］ nmol/mg prot, P<0.05).Compared with group C, group Eexhibited significant increases in the weight gained (［89.0±9.5］ vs ［99.9±4.1］ %, P<0.05) and sperm motility (［17.9±3.5］% vs ［27.3±5.3］ %, P<0.05) but a decrease in the content of MDA (［2.03±0.30］ nmol/mg prot vs ［1.52±0.41］ nmol/mg prot, P<0.05). CONCLUSIONS AST can improve spermquality in rats with ORN-inducedoligoasthenozoospermia, which may be associated with its enhancing effect on the antioxidant capacity of the epididymis.
Animals ; Antioxidants ; pharmacology ; Asthenozoospermia ; prevention & control ; Epididymis ; drug effects ; metabolism ; Male ; Oligospermia ; prevention & control ; Ornidazole ; Oxidative Stress ; Protective Agents ; pharmacology ; Radiation-Sensitizing Agents ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sperm Count ; Sperm Motility ; Spermatozoa ; drug effects ; metabolism ; Xanthophylls ; pharmacology

OBJECTIVETo explore the mechanisms of Qianjing Decoction in the treatment of oligoasthenospermia (OAS).

METHODSWe randomly divided 100 SPF male rats into five groups of equal number: normal, model, Huangjingzanyu, levocarnitine, and Qiangjing. OAS models were established in the animals followed by intragastrical administration of normal saline, ornidazole, Huangjingzanyu Capsules (200 mg per kg body weight per day), levocarnitine (100 mg per kg body weight per day), and Qianjing Decoction (10 g per kg body weight per day), respectively, qd, for 4 successive weeks. Then, we detected the concentration and motility of the epididymal sperm, obtained the contents of superoxide dismutase (SOD), malonaldehyde (MDA), glutathione peroxidase (GSH-Px), lactate dehydrogenase (LDH), α-glucosidase, and fructose in the epididymis, and determined the mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and succinate dehydrogenase (SDH) in the epididymal tissue of the rats by real-time PCR.

RESULTSThe concentration and motility of the epididymal sperm in the model, Huangjingzanyu, levocarnitine, and Qianging groups were (35.34 ± 4.22) x 10(6)/ml and (40.04 ± 7.05)%, (48.12 ± 5.56) x 10(6)/ml and (62.46 ± 7.12)%, (47.14 ± 4.87) x 10(6)/ml and (63.23 ± 6.34)%, and (50.25 ± 5.08) x 10(6)/ml and (66.34 ± 7.58)%, respectively, all significantly lower than in the normal group ([53.05 ± 4.55] x 10(6)/ml and [70.20 ± 8.54]%) (P < 0.05), but remarkably higher in the Huangjingzanyu, levocarnitine, and Qiangjing groups than in the model rats (P < 0.05). Compared with the thinned epididymal lumen walls, decreased sperm count, and disorderly and loose arrangement of the lumens in the OAS models, the rats in the Huangjingzanyu, levocarnitine, and Qiangjing groups showed evidently thicker epididymal lumen walls, with the lumens full of sperm cells and arranged regularly and compactly, similar to those of the normal rats. The levels of SOD and GSH-Px were significantly lower but that of MDA markedly higher in the model rats ([84.12 ± 23.25], [10.56 ± 3.02], and [14.04 ± 2.06] nmol/mg) than in the normal group ([110.04 ± 19.56], [17.25 ± 3.56], and [8.87 ± 1.35] nmol/mg) (P < 0.05), while the former two indexes remarkably higher and the latter one significantly lower in the animals treated with Qiangjing Decoction ([120.56 ± 23.68], [16.34 ± 3.12], and [8.45 ± 1.56] nmol/mg), Huangjingzanyu Capsules ([115.34 ± 21.35], [15.23 ± 3.67], and [8.33 ± 1.54] nmol/mg), and levocarnitine ([116.67 ± 22.67], [15.35 ± 3.45], and [8.05 ± 1.78] nmol/mg) than in the models (P < 0.05). The levels of fructose, LDH and α-glucosidase were decreased markedly in the OAS models ([100.22 ± 12.12] mg/[ ml x g], [322 ± 46.13] U/[ ml x g], and [10.48 ± 2.33] U/[ml x g]) as compared with the normal rats ([128.12 ± 13.45] mg/[ml x g], [428 ± 35.12] U/[ml x g], and [15.34 ± 3.12] U/[ ml x g]) (P < 0.05), remarkably higher in the rats treated with Qiangjing ([130.23 ± 13.67] mg/[ml x g] [455 ± 51.50] U/[ml x g], and [18.56 ± 4.67] U/[ml x g]), Huangjingzanyu ([124.16 ± 14.02] mg/[ml x g], [ 419 ± 43.14] U/[ml x g], and [17.64 ± 4.08] U/[ml x g]), and levocarnitine ([123.34 ± 14.02] mg/[ml x g], [430 ± 31.80] U/ [ml x g], and [16.85 ± 5.55] U/[ml x g]) than in the models (P < 0.05). The Nrf2 mRNA expression was significantly reduced in the models as compared with the normal rats (P < 0.05) but remarkably increased in the Huangingzanyu, Qiangjing and levocarnitine groups as compared with the model and normal animals (P < 0.05). The SDH mRNA expression was significantly lower in the model than in the normal rats (P < 0.05) but markedly elevated in the Huangjingzanyu, Qiangjing and levocarnitine groups as compared with the model and normal animals (P < 0.05), remarkably higher in the Qiangjing than in the Huangjingzanyu group (P < 0.05).

CONCLUSIONOrnidazole induces OAS in rats, which is closely associated with excessive oxidation and energy metabolism dysfunction. Qiangjing Decoction can improve and even reverse ornidazole-induced OAS in rats as well as improve the ultrastructure of their testicular and epididymal tissues. Antioxidation and improvement of energy metabolism are probably the action mechanisms of Qiangjing Decoction in the treatment of OAS.

Animals ; Antioxidants ; Asthenozoospermia ; chemically induced ; drug therapy ; metabolism ; Carnitine ; pharmacology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Energy Metabolism ; drug effects ; Epididymis ; metabolism ; Glutathione Peroxidase ; metabolism ; L-Lactate Dehydrogenase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Oligospermia ; chemically induced ; drug therapy ; metabolism ; Ornidazole ; Random Allocation ; Rats ; Sperm Count ; Sperm Motility ; Spermatozoa ; drug effects ; physiology ; Succinate Dehydrogenase ; metabolism ; Superoxide Dismutase ; metabolism ; alpha-Glucosidases ; metabolism

OBJECTIVETo investigate the distribution of ornidazole in the salivary and serum of healthy adults and explore the feasibility of monitoring serum drug concentration with salivary.

METHODSSix volunteers received a single dose of 0.6 g ornidazole via intravenous infusion. The concentrations of ornidazole in the saliva and serum were assayed by high-performance liquid chomatography, and the correlation of the drug concentrations in saliva to that in serum was analyzed.

RESULTSThe concentration of ornidazole in the saliva was strongly associated with that in the serum (r = 0.825-0.969), and the ratio of saliva-to-serum concentration (S/P) of ornidazole was 0.99 ± 0.13.

CONCLUSIONDetection of saliva ornidazole concentration is feasible for monitoring the therapeutic concentration of ornidazole.

Adult ; Anti-Bacterial Agents ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Feasibility Studies ; Female ; Humans ; Male ; Ornidazole ; analysis ; blood ; pharmacokinetics ; Saliva ; metabolism ; Young Adult

PURPOSE: In a previous study, we have shown that anticancer agents inhibiting topoisomerases improve survival of tumor cells under hypoxic condition. In the present study, we evaluated whether and how cell survival effect of the anticancer agents under hypoxic conditions could be eliminated by the addition of nitroimidazoles, a class of bioreductive agents. METHODS: Human hepatocellular carcinoma cells (HepG2) were incubated with different combinations of pimonidazole (1~1,000 microg/ml) and doxorubicin (0.1 or 1 microg/ml) concentrations under different O2 concentrations [1, 3, 5, 10 and 21 O2]. Then cell numbers, glucose concentrations and lactic acid concentrations in the medium were measured, and DNA fragmentation assay was performed. Finally, different combinations of nitroimidazoles, such as pimonidazole, misonidazole, etanidazole, tinidazole, metronidazole, ornidazole or dimetridazole, and anticancer agents, such as doxorubicin, campothecin, epirubicin, dactinomycin, etoposide or mitomycin C was added to the cell culture medium under hypoxic conditions (1% O2). RESULTS: Pimonidazole at a concentration of 100 microg/ml eliminated cell survival effect of doxorubicin at the concentrations of 0.1 and 1 microg/ml under hypoxic condition (1% O2) by promoting apoptosis. Almost all the cells died even after 24 hours of incubation for all the oxygen concentrations at a combination of 100 microg/ml pimonidazole and 1 microg/ml doxorubicin. Finally, pimonidazole at a concentration of 100 microg/ml, and misonidazole or etanidazole at a concentration of 1,000 microg/ml eliminated cell survival effect of all the anticancer agents tested under hypoxic condition. CONCLUSION: Combination therapy of doxorubicin (adriamycin) with pimonidazole can maximize dororubicin efficacy by eliminating cell survival effect of doxorubicin under hypoxic conditions in treating solid tumors, such as breast cancer.
Anoxia ; Antineoplastic Agents ; Apoptosis ; Breast Neoplasms ; Carcinoma, Hepatocellular ; Cell Count ; Cell Culture Techniques ; Cell Survival ; Dactinomycin ; Dimetridazole ; DNA Fragmentation ; Doxorubicin ; Epirubicin ; Etanidazole ; Etoposide ; Glucose ; Humans ; Lactic Acid ; Metronidazole ; Misonidazole ; Mitomycin ; Nitroimidazoles ; Ornidazole ; Oxygen ; Tinidazole

OBJECTIVETo investigate the protective effect of L-carnitine on the testis and epididymis against ornidazole (ORN)-induced injury in male rats.

METHODSForty male SD rats weighing 200 -230 g were randomly divided into 5 groups, Group A treated with 0.5% sodium carboxymethyl cellulose, and Groups B, C, D and E with ORN at the daily dose of 400 mg/kg, 800 mg/kg, 400 mg/kg plus LC 100 mg/kg and 800 mg/kg plus LC 100 mg/kg, respectively, all by oral gavage for 20 days continuously. Twenty-four hours after the last administration, all the rats were put to death, their testes and epididymides harvested, weighed and subjected to HE staining. The indexes of the testes and epididymides were obtained and their histopathological changes observed.

RESULTSCompared with Group A, Groups B and C showed significant decreases in the indexes of the testis and epididymis (P < 0.05 and P < 0.01), while Group D exhibited no difference and Group E extremely significant difference (P < 0.01). HE staining revealed that the spermatogenic cells at all levels of testicular seminiferous tubules were neatly arranged in Group B, caduceus in some seminiferous tubules, with decreased number of sperm and sporadic spermatogenic cells in the epididymal duct. Necrotic and caduceus spermatogenic cells were observed in the seminiferous tubules of Group C, with significantly decreased number of sperm and lots of non-sperm cell components in the epididymal duct. No obvious changes were found in the testicular seminiferous tubules, nor evident reduction in the number of sperm in the epididymal duct of Group D. Group E showed decreased number of sperm in the testicular seminiferous tubules, necrotic and caduceus spermatogenic cells, obviously reduced number of sperm and a lot of non-sperm cell components in the epididymal duct.

CONCLUSIONORC can induce histopathological changes in the testis and epididymis of male rats, and L-carnitine plays a role in protecting the testis and epididymis from ORN-induced injury in male rats.

Animals ; Carnitine ; pharmacology ; Epididymis ; drug effects ; pathology ; Male ; Ornidazole ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Testis ; drug effects ; pathology

OBJECTIVETo explore the protective effect of L-carnitine (LC) on the reproductive function of male rats with asthenospermia induced by ornidazole (ORN).

METHODSForty male SD rats (200-230 g) were randomly divided into Groups A (control: 0.5% carboxymethylcellulose solution), B (medium-dose ORN: 400 mg/kg/d), C (medium-dose ORN + LC: ORN 400 mg/kg/d + LC 100 mg/kg/d), D (high-dose ORN: 800 mg/kg/d), and E (high-dose ORN + LC: ORN 800 mg/kg/d + LC 100 mg/kg/d). All the rats were treated via gastric gavage for 20 days consecutively, and then killed for the detection of sperm motility and the sperm count of the cauda epididymis.

RESULTSCompared with Group A, there was a significant decrease in sperm motility and sperm count in Groups B and D (P < 0.05), while Group C showed a significant increase in both the parameters as compared with B (P < 0.05), but with no significant difference from A (P > 0.05). Group E exhibited no obvious improvement in sperm motility and sperm count, with no difference from D (P > 0.05).

CONCLUSIONL-carnitine can improve the sperm motility and sperm count of the male rats with ornidazole-induced asthenospermia.

Animals ; Asthenozoospermia ; chemically induced ; drug therapy ; Carnitine ; therapeutic use ; Male ; Ornidazole ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Sperm Count ; Sperm Motility ; Treatment Outcome

OBJECTIVETo investigate the effects of urokinase-type plasminogen activator (uPA) on the reproductive function of the male rats with ornidazole-induced infertility.

METHODSFifty 10-12 weeks old adult male Sprague-Dawley rats were randomly divided into five groups: low-dosage uPA (330 IU/[kg x d]), mid-dosage uPA (1000 IU/[kg x d]), high-dosage uPA (3000 IU/[kg x d]), ornidazole (400 mg/[kg x d]) and control (0.5% Carboxymethylcellulose solution). The ornidazole group was treated by gastric gavage, and the rats in the uPA groups given both ornidazole by gastric gavage and uPA by intraperitoneal injection at the same time. All the rats were treated for 20 days consecutively, followed by copulation experiment. The rats were sacrificed and the reproductive system explored.

RESULTSThe percentage of motile sperm and the number of embryos in the high-dosage uPA group increased significantly (P < 0.01) compared with the ornidazole group.

CONCLUSIONuPA can antagonize ornidazole-induced infertility in male rats. The effect might be attributed to the improvement of sperm motile function by uPA.

Animals ; Dose-Response Relationship, Drug ; Infertility, Male ; chemically induced ; drug therapy ; physiopathology ; Male ; Ornidazole ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reproduction ; drug effects ; Sperm Motility ; drug effects ; Urokinase-Type Plasminogen Activator ; pharmacology

OBJECTIVETo explore the reductive effect of ornidazole on sperm motility in rats and its mechanism of action.

METHODSTwenty rats were randomly divided into three groups, a low dosage group (LD group, n = 5), a high dosage group (HD group, n = 8) and a normal control group (n = 7). Ornidazole (200 mg/kg, 400 mg/kg) was given to the LD and HD groups, and 0.5% carboxymethylcellulose sodium (CMC) administered to the normal control, all for 20 consecutive days. Immediately after, sperm density, motility and the morphological changes of the testis and epidiclymis were measured, and the concentrations of lactate dehydrogenase (LDH), alpha-glycosidase, malondialdehyde (MDA) and fructose in the testis and epididymis tissues were monitored.

RESULTSCompared with the normal control, there were no obvious changes in sperm density (P > 0.05), but a significant decrease in sperm motility in the LD and HD groups (P < 0.01), and the concentration of LDH obviously declined (P < 0.01) while that of MDA distinctly increased in the HD group (P < 0.05).

CONCLUSIONSpermatogenic cells could be damaged by the increase of inhibiting MDA, while sperm motility could be decreased by inhibiting energetic transferase or non-protein substance in the epididymis. This might be one of the mechanisms of ornidazole on weak sperm models in rats.

Animals ; Dose-Response Relationship, Drug ; Epididymis ; cytology ; Male ; Ornidazole ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sperm Count ; Sperm Motility ; drug effects ; Spermatozoa ; drug effects ; Testis ; cytology

Trichomoniasis is a sexually transmitted disease by Trichomonas vaginalis infection that may be associated with preterm delivery and low birth weight in the newborn infants. T. vaginalis may be transmitted to neonates during passage through an infected birth canal and neonatal infection is usually self-limiting course, but rare cases of symptomatic neonatal infection such as vaginitis, urinary tract infection and respiratory infection have been reported. We experienced a case of symptomatic neonatal trichomoniasis which was confirmed by wet mount examination of vaginal discharge and urine specimens in premature baby with intrauterine growth retardation. The patient had complete resolution of symptoms such as vaginal discharge and pyuria after treatment with ornidazole (tiberalR). We report this case with a brief review of the related literatures.
Fetal Growth Retardation ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Ornidazole ; Parturition ; Pyuria ; Sexually Transmitted Diseases ; Trichomonas vaginalis ; Urinary Tract Infections ; Vaginal Discharge ; Vaginitis