allopurinol and Infertility--Male

To explore the mischief mechanism of oxidative stress in the varicocele (VC).. Serum was taken from the spermatic and peripheral veins on ligation of the internal spermatic veins in 28 infertile males with VC. Experimental VC was established in male rats by partial ligation of the left renal vein. And testis tissue was taken three months after operation. The nitric oxide(NO), nitric oxide synthetase (NOS), xanthine oxidase (XO), lactic acid(Lac) and lactic dehydrogenase (LDH) in the serum of 28 infertile males with VC and the testis tissue of the VC rats were detected by spectrophotometry.. NO, NOS, XO and Lac in the serum of internal spermatic veins in the infertile males with VC were significantly higher than in the serum of peripheral veins in the VC patients (P < 0.01, P < 0.05). LDH was lower than that in peripheral serum. NO and XO of the left testis tissue in the VC rats were higher compared with the control group (P < 0.01). Lac in the left testis of the VC rats was lower than that in the control group rats (P < 0.01).. NO, NOS and XO in the serum of the VC patients and in the testis tissues of the VC rats were increased, and Lac and LDH were changed obviously, which might not only disturb spermatogenesis, but also inhibit sperm motility. Therefore they might be one of the causes of infertility in VC patients.

Topics: Adult; Animals; Humans; Infertility, Male; Male; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress; Rats; Rats, Wistar; Varicocele; Xanthine Oxidase

We have studied the oxidative status of 155 semen samples, 95 originating from healthy individuals and 60 from infertile patients, which were subdivided into two groups: (a) normozoospermic with genitourinary tract infection (GTI); and (b) with pathological spermiogram and GTI. Several phases of infection were observed: with bacterial presence only, bacteria and leukocytes, and leukocytes only, following the routine inflammatory pattern. Leukocyte numbers, bacterial strains, pro- and anti-oxidants, and selected pro-inflammatory cytokines (IL-1 beta, IL-6, IL-8 and TNF-alpha) were studied. Additionally, two oxido-sensitive indices were created (SOD/XO and CAT/XO) in order to follow particular phases of semen infection in two subgroups of patients. Different patterns of activities of pro- and anti-oxidant substances, as well as cytokines, were observed in the studied populations. It was reflected mainly by elevated XO activity in a group of patients with a pathological spermiogram while, in a group of patients with GTI and normozoospermia, xanthine oxidase was normal. In the latter group, oxido-sensitive indices were elevated in favour of anti-oxidants; similarly, this occurred with IL-6 levels in comparison to healthy controls. It appears therefore that normozoospermic semen recovers better after infection than pathological semen. Perhaps, IL-6 secretion might be helpful in the observed recovery?

Topics: Antioxidants; Bacterial Infections; Catalase; Cytokines; Genital Diseases, Male; Humans; Infertility, Male; Leukocyte Count; Male; Semen; Superoxide Dismutase; Xanthine Oxidase

Apoptotic degeneration of germ cells in cryptorchid testis is associated with an increased level of reactive oxygen species, and may be prevented by antioxidant treatment. The objective of this study was to investigate whether xanthine oxidase inhibitors could confer such protection. Unilateral cryptorchidism was surgically induced in the immature rats, which were then left untreated or treated with xanthine oxidase inhibitors, and the testes were evaluated 7 days after the operation. In the control group, the weight of the cryptorchid testis was decreased to 47% of that of the contralateral scrotal testis. However, administration of a xanthine oxidase inhibitor allopurinol (> or = 1 mg/kg/day) significantly attenuated weight reduction of the cryptorchid testis (68-77% of the contralateral scrotal testis, P < 0.01 versus control). Another highly specific xanthine oxidase inhibitor, BOF-4272, also attenuated cryptorchidism-induced testis regression. The effects of allopurinol were associated with decreased apoptosis in germ cells as evaluated by in-situ staining of fragmented DNA. In testicular cells cultured at 37 degrees C, either allopurinol or BOF-4272 prevented DNA cleavage characteristic of apoptosis. In conclusion, xanthine oxidase inhibitors can inhibit germ cell apoptosis induced by experimental cryptorchidism, and may be considered for treatment of male infertility associated with heat stress.

Topics: Allopurinol; Animals; Apoptosis; Cells, Cultured; Cryptorchidism; Enzyme Inhibitors; Hot Temperature; Infertility, Male; Male; Organ Size; Rats; Rats, Wistar; Reactive Oxygen Species; Testis; Triazines; Xanthine Oxidase

Seminal plasma protects spermatozoa from the detrimental effects of reactive oxygen species such as hydrogen peroxide. We investigated the lucigenin-dependent chemiluminescence in cell-free seminal plasma from andrological patients. The seminal plasma was separated from cells by centrifugation. In all seminal plasmas studied lucigenin-dependent chemiluminescence (LCL) was detected. The LCL showed a strong pH-dependence. The signal was stable if samples were stored at +4 degrees C for up to 4 days or up to 8 days at -80 degrees C. Filtration of the samples (0.45 and 0.22 microm pore size) did not lower their luminescence. The addition of superoxide dismutase (SOD) and ascorbic acid oxidase (AAO) lowered LCL nearly to baseline values while trolox and desferal showed moderate effect, whereas allopurinol had no effect. Electron paramagnetic resonance spectroscopy demonstrated ascorbyl radicals in seminal plasma. Physiological concentrations of ascorbic acid yielded SOD-inhibitable lucigenin-chemiluminescence. The nitroblue-tetrazolium assay showed that ascorbic acid in buffer solution produced formazan. Superoxide-anion radicals were not detected in seminal plasma by the spin-trap DEPMPO due to their low steady state concentration. It is concluded that in seminal plasma ascorbate reacts with molecular oxygen yielding ascorbyl radicals and superoxide anion. If lucigenin is added to seminal plasma, reducing substances present, such as ascorbate, reduce lucigenin to the corresponding radical; this radical reacts with molecular oxygen and also forms O2-. So LCL in human seminal plasma results from the autoxidation of ascorbate and the oxidation of the reduced lucigenin. While the physiological relevance of the former mechanism is unknown, the latter is an artifact.

Topics: Acridines; Adult; Allopurinol; Antioxidants; Ascorbate Oxidase; Ascorbic Acid; Chromans; Deferoxamine; Electron Spin Resonance Spectroscopy; Free Radicals; Humans; Hydrogen-Ion Concentration; Infertility, Male; Luminescent Measurements; Male; Oxidants; Oxidation-Reduction; Oxygen; Oxygen Consumption; Reactive Oxygen Species; Semen; Semen Preservation; Superoxide Dismutase; Temperature

This study was designed to investigate the relationship between the effects of testicular reactive oxygen species (ROS) levels and testicular histology on infertile patients with the aid of xanthine oxidase system and testicular tissue malondialdehyde levels. Forty patients with idiopathic infertility constituted our study group. Bilateral testicular biopsies were performed and spermatogenesis was assessed histopathologically. Patients were divided into 4 groups according to spermatogenic pattern (normal spermatogenesis; hypospermatogenesis; maturation arrest; Sertoli cell only syndrome). Testicular tissue xanthine oxidase and malondialdehyde (MDA) concentrations were analyzed in each sample by spectrophotometric assay and thiobarbituric acid reaction assay, respectively. Testicular tissue MDA and xanthine oxidase concentrations were not statistically different in patients having normal spermatogenesis, with respect to Sertoli cell only syndrome, maturation arrest and hypospermatogenesis, respectively. As a result of our study we think that there are still some factors other than ROS which may be important contributors to spermatogenetic injury that need to be examined.

Topics: Adult; Biopsy; Humans; Infertility, Male; Male; Malondialdehyde; Reactive Oxygen Species; Spectrophotometry; Spermatogenesis; Testis; Thiobarbiturates; Xanthine Oxidase

A range of compounds with a role in oxidative stress were measured in ejaculates from 40 normozoospermic individuals and 93 infertile males. Ejaculates were classified according to WHO criteria. Seminal plasma and the sperm cell fraction were assessed separately for superoxide dismutase (SOD), catalase, xanthine oxidase, capability for singlet oxygen trapping and content of thiobarbituric acid-reactive substances (TBARS). Pathological cases defined as oligozoospermia, asthenozoospermia, or teratozoospermia revealed different backgrounds of oxidative stress as reflected by different levels of tested substances in every type of sperm pathology. In the majority of abnormal ejaculates, a significant increase in intracellular activity of SOD, decreased intracellular levels of catalase, elevated levels of xanthine oxidase and TBARS, and severely impaired singlet oxygen trapping were observed when compared to normozoospermic ejaculates. Interrelationships between SOD and TBARS, and between xanthine oxidase and catalase, appeared to be of key importance when analysed separately in seminal plasma and in spermatozoa or in a combination of both. Elevated xanthine oxidase levels and low capacity for singlet oxygen trapping are statistically significant factors for the evaluation of male infertility which can develop as a result of persistent oxidative stress.

Topics: Antioxidants; Catalase; Humans; Infertility, Male; Male; Reactive Oxygen Species; Semen; Spermatozoa; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Xanthine Oxidase

Seminal plasma from ejaculates of 10 healthy, fertile volunteers and 63 infertile males was analysed for superoxide dismutase (SOD) and xanthine oxidase (XO) activities using a chemiluminometer. There was not statistically significant difference in the activity of either enzyme between control and infertile populations (113 +/- 74 IU/ml for SOD and 1.17 +/- 0.52 IU/ml for XO) in samples from normozoospermic ejaculates. Sperm progressive motility was positively correlated with SOD activity in seminal plasma of corresponding ejaculates (P < 0.05) and negatively with XO activity (P < 0.001). An 'oxido-sensitive' index was defined as the SOD/XO ratio and was found to be inversely related to sperm progressive motility samples (P < 0.01). Analysing this index among all tested samples of semen including those with pathological spermiograms, as well as normospermic (N) samples we found statistically significant (elevated) differences in oligoasthenoteratospermia (OAT) in comparison with N (P <0.05); OAT samples were also significantly different from oligospermic (O) and oligoteratospermic (OT) samples (P < 0.05). This suggests that the 'oxido-sensitive' index of seminal plasma may be a simple diagnostic factor, useful in the determination of male infertility.

Topics: Clinical Enzyme Tests; Humans; Infertility, Male; Luminescent Measurements; Male; Predictive Value of Tests; Reference Values; Semen; Sperm Motility; Superoxide Dismutase; Xanthine Oxidase

The oxidative and reductive stresses within the varicocele veins were estimated. Nitric oxide synthase and xanthine oxidase activities, as well as nitric oxide, S-nitrosothiols and superoxide release within the spermatic vein in patients with varicocele, and the role of the noxious oxidant peroxynitrite formed from nitric oxide and superoxide in sperm dysfunction were determined.. Whole blood samples were drawn from a peripheral vein and a dilated varicocele vein before ligation. Nitric oxide synthase, xanthine oxidase, nitric oxide and peroxynitrite were measured by novel spectro-fluorophotometric methods. S-nitrosothiols were estimated by a luminol-chemiluminescence method. Serum and red blood cell antioxidant capacity was determined by a chemiluminescence reaction.. Serum nitric oxide synthase and xanthine oxidase activities, as well as nitric oxide, peroxynitrite and S-nitrosothiol levels were greater in the spermatic vein compared to the peripheral vein. Serum antioxidant capacity was greater in varicocele veins compared to peripheral veins. In contrast, the antioxidant capacity of red blood cells was less in the varicocele veins, which was consistent with an increased rate of peroxynitrite production.. Our data suggest a high oxidative stress due to the release of nitric oxide synthase and xanthine oxidase within the dilated spermatic vein. The reaction resulted in dramatic formation of nitric oxide, peroxynitrite and S-nitrosothiols, which are biologically active. Formation of peroxynitrite from the reaction of nitric oxide with superoxide could be a causative factor for impaired sperm function in patients with varicocele.

Topics: Humans; Infertility, Male; Male; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Oxidation-Reduction; Penis; Spermatozoa; Sulfhydryl Compounds; Varicocele; Veins; Xanthine Oxidase

Topics: Adult; Allopurinol; Colchicine; Female; Humans; Infertility, Male; Male; Middle Aged; Sperm-Ovum Interactions; Sulfasalazine