Can testosterone level be a good predictor of late-onset hypogonadism?

Androgens are essential for the development and growth of the genitalia. They regulate the erectile physiology by multiple mechanisms. Several studies have examined associations among sex hormones' serum levels, erectile function and sex drive. We sought to identify a protocol for using testosterone in men with erectile dysfunction and late-onset hypogonadism (LOH). During a 16-month period, men with erectile dysfunction who presented to the andrology clinic were selected. They underwent a complete physical examination and filled out the International Index of Erectile Function-5 questionnaire. Serum luteinising hormone (LH) and testosterone levels were evaluated. Patients received a single intramuscular injection of 250 mg testosterone. Thereafter, serum levels of LH and testosterone were measured 3 weeks later. The mean age was 53 years old. After treating patients with testosterone, 45 (94%) showed improvement in LOH symptoms including libido, loss of energy, irritability and quality of life. The mean International Index of Erectile Function was 9 and 13.1, prior to and after treatment respectively. Mean serum testosterone levels before and after treatment were 4.2 and 4.1 ng ml(-1) respectively (P = 0.849). Mean serum LH revealed a significant decrease after the study (P = 0.004) (6.12 and 5.1 ng ml(-1) , before and after the study respectively). Our findings suggested that testosterone replacement therapy improves libido and LOH symptoms in individuals with almost normal or lower limit normal value of serum testosterone levels.

Paternal exposure to arsenic resulted in oxidative stress, autophagy, and mitochondrial impairments in the HPG axis of pubertal male offspring.

Despite the knowledge of AS-induced reprotoxicity, the literature concerning arsenic trioxide (As2O3)-induced oxidative stress and consequent intracellular events, like autophagy process, in the hypothalamic-pituitary- gonadal (HPG) axis of F1- pubertal male mice is sparse to date. Hence, we made an attempt to study the reproductive toxicities and the underlying mechanisms induced by As2O3 in the HPG axis of pubertal F1- male mice in correlation with oxidative stress-induced autophagy. Parental mice were challenged with As2O3 (0, 0.2, 2, and 20 ppm) from five weeks before mating, and continued till puberty age for the male pups. It was recorded that higher As2O3 doses (2 and 20 ppm) were a potent inducer of oxidative stress and autophagy in the HPG axis. Concomitant with a decrease on mean body weight, total antioxidant capacity, and stereology indices, an increase in the number of MDC-labeled autophagic vacuoles, and MDA/GSH ratio in HPG axis of pubertal F1- male mice which were exposed to higher As2O3 doses was observed. Meanwhile, concomitant with a dose-dependent increment in the gene expression of ATG3, ATG5, Beclin, as well as protein expression of P62, ATG12, and Beclin in HPG axis tissues; a dose-dependent decrease in PI3K and mTOR gene expression was recorded in the HPG tissues of pubertal F1-males. Altogether, our observations suggest that higher doses of As2O3 have detrimental effects on the functionality of HPG axis in pubertal male mice offspring by increasing MDA/GSH ratio and autophagic cell death-related genes and proteins, as well as by reducing total antioxidant capacity.

Is immunosuppression, induced by neonatal thymectomy, compatible with poor reproductive performance in adult male rats?

With increasing knowledge that the immune system has a major impact on reproductive health, the potential for cells arising in organs such as the thymus to alleviate oxidative stress has been revealed. This study addresses the impact of neonatal thymectomy on male reproductive function in pubertal and adult animals. Neonatal Sprague Dawley rats were allotted to four treatments consisting of fully thymectomized, partially thymectomized, intact, and sham-operated rats. Half of the rats in each treatment were sacrificed at 40 and the other half at 80 days of age. Testicular volume, ventral prostate and spleen weight, several sperm attributes (concentration, motility, livability, membrane integrity, sperm penetration into mucus, total antioxidant capacity, mitochondrial dehydrogenase activity), plasma superoxide dismutase, glutathione, and testosterone level as well as fertility decreased in thymectomized rats. Adrenal gland weight, sperm malondialdehyde level, indices of oxidative stress, sperm abnormality, testicular and sperm lipid peroxidation, protein carbonylation, and sperm reactive oxygen species generation increased in thymectomized rats. In thymectomized rats, the testes contained high levels of malondialdehyde but low levels of glutathione and ferric-reducing antioxidant power. Epididymal sperm reactive oxygen species, blood lipid peroxidation, and oxidative stress indices in blood and spermatozoa were highest in fully thymectomized, intermediate in partially thymectomized, and lowest in both pubertal and mature control rats. Blood levels of superoxide dismutase, lipid peroxidation indices, and testosterone, and mitochondrial adenosine triphosphate and dehydrogenase activities in epididymal spermatozoa were lowest in fully thymectomized, intermediate in partially thymectomized, and highest in both pubertal and mature control rats. The data indicated that increased oxidative stress and mitochondrial dysfunction might play a role in the mechanism of immunosuppression-induced testicular and sperm abnormalities.

Hydrolysis of individual isomers of fluorogenic pyrethroid analogs by mutant carboxylesterases from Lucilia cuprina.

We previously showed that wild-type E3 carboxylesterase of Lucilia cuprina has high activity against Type 1 pyrethroids but much less for the bulkier, alpha-cyano containing Type 2 pyrethroids. Both Types have at least two optical centres and, at least for the Type 1 compounds, we found that wild-type E3 strongly prefers the less insecticidal configurations of the acyl group. However, substitutions to smaller residues at two sites in the acyl pocket of the enzyme substantially increased overall activity, particularly for the more insecticidal isomers. Here we extend these analyses to Type 2 pyrethroids by using fluorogenic analogs of all the diastereomers of cypermethrin and fenvalerate. Wild-type E3 hydrolysed some of these appreciably, but, again, not those corresponding to the most insecticidal isomers. Mutations in the leaving group pocket or oxyanion hole were again generally neutral or deleterious. However, the two sets of mutants in the acyl pocket again improved activity for the more insecticidal acyl group arrangements as well as for the more insecticidal configuration of the cyano moiety on the leaving group. The activities of the best mutant enzyme against the analogs of the most insecticidal isomers of cypermethrin and fenvalerate were more than ten and a hundred fold higher, respectively, than those of wild-type. The implications for resistance development are discussed.

Evaluating the Role of Drug Metabolism and Reactive Intermediates in Trazodone-Induced Cytotoxicity toward Freshly-Isolated Rat Hepatocytes.

Background: Trazodone is an antidepressant agent widely administered for the treatment of depressive disorders. On the other hand, several cases of hepatic injury have been reported after Trazodone administration. Although the precise mechanism(s) of trazodone-induced liver injury is not known, some investigations proposed the role of reactive intermediates in this complication. This study was designed to investigate the role of reactive metabolites in hepatocytes injury induced by trazodone. Methods: Isolated rat hepatocytes were prepared by the method of collagenase enzyme perfusion via the portal vein. Cells were treated with trazodone, its cytotoxic metabolite, and different enzyme inhibitors and cytoprotective agents. Results: It was found that trazodone was toxic towards hepatocytes and caused 50% cell death after 2 h of incubation at a dose of 450 µM. The trazodone postulated reactive metabolite; m-chlorophenyl piperazine (m-CPP) was less toxic and caused 50% cell death at a dose of 750 µM at a similar time period. Cellular glutathione (GSH) depletion and lipid peroxidation were detected when hepatocytes were treated with trazodone and/or m-CPP. Depleting hepatocytes GSH beforehand, increased cytotoxicity of both trazodone and m-CPP. Troleandomycin as the CYP3A4 inhibitor prevented cytotoxicity of trazodone but slightly affected m-CPP-induced cell injury. Inhibition of CYP2D6 by quinidine and cimetidine increased the cytotoxicity of both trazodone and m-CPP. Antioxidants and ATP suppliers slightly prevented cytotoxicity of trazodone and m-CPP. Conclusion: As inhibitors of CYP3A4 and 2D6 affected trazodone cytotoxicity, it is suggested that trazodone -induced cytotoxicity, at least in part, is mediated by its reactive metabolites.

Hydrolysis of organophosphorus insecticides by in vitro modified carboxylesterase E3 from Lucilia cuprina.

Resistance of the blowfly, Lucilia cuprina, to organophosphorus (OP) insecticides is due to mutations in LcalphaE7, the gene encoding carboxylesterase E3, that enhance the enzyme's ability to hydrolyse insecticides. Two mutations occur naturally, G137D in the oxyanion hole of the esterase, and W251L in the acyl binding pocket. Previous in vitro mutagenesis and expression of these modifications to the cloned gene have confirmed their functional significance. G137D enhances hydrolysis of diethyl and dimethyl phosphates by 55- and 33-fold, respectively. W251L increases dimethyl phosphate hydrolysis similarly, but only 10-fold for the diethyl homolog; unlike G137D however, it also retains ability to hydrolyse carboxylesters in the leaving group of malathion (malathion carboxylesterase, MCE), conferring strong resistance to this compound. In the present work, we substituted these and nearby amino acids by others expected to affect the efficiency of the enzyme. Changing G137 to glutamate or histidine was less effective than aspartate in improving OP hydrolase activity and like G137D, it diminished MCE activity, primarily through increases in Km. Various substitutions of W251 to other smaller residues had a broadly similar effect to W251L on OP hydrolase and MCE activities, but at least two were quantitatively better in kinetic parameters relating to malathion resistance. One, W251G, which occurs naturally in a malathion resistant hymenopterous parasitoid, improved MCE activity more than 20-fold. Mutations at other sites near the bottom of the catalytic cleft generally diminished OP hydrolase and MCE activities but one, F309L, also yielded some improvements in OP hydrolase activities. The results are discussed in relation to likely steric effects on enzyme-substrate interactions and future evolution of this gene.

Amodiaquine-induced toxicity in isolated rat hepatocytes and the cytoprotective effects of taurine and/or N-acetyl cysteine.

Amodiaquine is an antimalarial drug used in the prophylaxis and treatment of this disease. However, hepatotoxicity as a life-threatening adverse effect is associated with its clinical use. We evaluated amodiaquine-induced toxicity in isolated rat hepatocytes as an in vitro model for studying drug-induced hepatotoxicity. This study attempts to investigate the protective effects of taurine and N-acetyl cysteine against the cytotoxicity induced by amodiaquine. Hepatocytes were prepared by the method of collagenase enzyme perfusion via portal vein. This technique is based on liver perfusion with collagenase after removal of calcium ion (Ca(2+)) with a chelator (ethylene glycol tetraacetic acid (EGTA) 0.5 mM). Cells were treated with different concentrations of amodiaquine, taurine and N-acetyl cysteine. Cell death, protein carbonylation, reactive oxygen species formation, lipid peroxidation, and mitochondrial depolarization were assessed as toxicity markers. Amodiaquine cytotoxic mechanism involved protein carbonylation as well as reactive oxygen species formation and lipid peroxidation. In addition, mitochondria seem to be a target for amodiaquine to induce cellular damage. Administration of taurine (200 µM) and/or N-acetyl cysteine (200 µM) reduced oxidative stress, lipid peroxidation and protein carbonylation caused by amodiaquine. Furthermore, amodiaquine-induced mitochondrial injury was significantly mitigated by taurine and/or N-acetyl cysteine. In glutathione-depleted cells, only N-acetyl cysteine protected hepatocytes against amodiaquine, and taurine showed no protective properties in this situation. Taurine and N-acetyl cysteine protect hepatocytes against amodiaquine probably via their antioxidant properties and counteracting oxidative stress.

Histopathological changes in the liver and kidney tissues of Wistar albino rat exposed to fenitrothion.

The aim of this study was to investigate the dose-related effects of fenitrothion (FNT) on the liver and kidney. The study was conducted on 8-week-old male Wistar rats that were divided into four groups (three experimental groups and one control group) and were treated orally with different doses (25, 50, 100 mg/kg) of FNT for 28 consecutive days. After treatment, the rats were anesthetized with ether and liver and kidney samples were taken for histological studies. The results showed that the histopathological changes in the liver were mainly represented by parenchymatous degeneration of hepatocytes with mild necrosis, leukocytic infiltration in the portal area, severe congestion, and hemorrhage. These changes were dose dependent. Marked tubular dilation, hydropic degeneration in tubular epithelium, moderate congestion, and hemorrhage in the cortical and medulla part of the kidney were recorded. Histopathologic examination of the liver and kidney indicated a significant injury only in rats receiving 100 mg/kg FNT.

Salt pretreatment enhance salt tolerance in Zea mays L. seedlings.

Recent molecular studies show that genetic factors of salt tolerance in halophytes exist in glycophytes too, but they are not active. If these plants expose to low level salt stress these factors may become active and cause plants acclimation to higher salt stresses. So because of the importance of these findings in this research the effect of salt pretreatment has been examined in Zea mays seedlings. To do the experiment four day old Zea mays seedlings (Var. single cross 704) pretreated with 50 mM NaCl for the period of 20 h. Then they were transferred to 200 and 300 mM NaCl for 48 h. At the end of treatment roots and shoots of seedlings were harvested separately. The changes of K+ -leakage, the amount of malondialdehyde, proline, soluble sugars and the Hill reaction rate were analyzed. The results indicated that the amount of K+ -leakage and malondialdehyde (MDA) have been increased because of salt-induced lipid peroxidation and membrane unstability. Soluble sugars and proline as osmoregulators has been increased in stress condition and in pretreated plants with NaCl were the highest. The rate of Hill reaction was reduced significantly in stressed plants. Therefore we concluded that salt stress causes serious physiological and biochemical damages in plants and salt pretreatment enhances tolerance mechanisms of plants and help them to tolerate salt stress and grow on salty environments.

Concentration of heavy metals in different tissues of Astacus leptodactylus from Aras dam of Iran.

Due to different human activities in the vicinities of Aras dam, various pollutants such as heavy metals are entered into the reservoir and thus polluting the aquatic ecosystem. As a result, this heavy metal is accumulated in the tissues of Astacus leptodoctylus, which is considered as one the abundant species of crayfish that has got important food values and is of economic importance due to its export to other countries. In this research, the bioaccumulation of heavy metals in different tissues of this animal is taken into consideration. The concentration of Fe, Cu, Zn, Mn, Pb, Ni, Co and Cr among the tissues of female and male Astacus leptodactylus has been determined. The highest concentration of Cu and Fe was found in the gills and the highest level of Zn was found in hepatopancreas. Besides, the highest Mn concentration was recognized in exoskeleton. Furthermore, no significant difference was found between the male and female crayfish in the concentration of the heavy metals in their tissues, except for the concentration of some of the metals such as Fe in some of the tissues such as hepatopancreas.

Effects of lead nitrate (PbNO3) on the glucose and cortisol hormone levels in common carp, Cyprinus carpio.

The objective of this study was to evaluate the possible effects of PbNO3 exposure on variations of glucose and cortisol levels in Cyprinus carpio. Fish were subjected to two sub-lethal concentrations of PbNO3 for 14 days. Blood samples were isolated from the fish following the exposure, to measure the levels of cortisol and glucose compared to the control group. We found significant increases (p<0.05) in the levels of blood cortisol in two groups of fish after 14 days of exposure to two concentrations of PbNO3 (1.3 and 2.6 mg L (-1)) The results showed significant increases in the glucose levels of both fish groups exposed for 14 days In the later treatment, the rate of increase in group II (exposed to 2.6 mg L(-1) PbNO3) was higher than that of group I (exposed to 1.3 mg L(-1) PbNO3) (P = 0 compare to P = 0.007). Present findings attest that exposing to waterborne lead would affect the levels of both glucose and cortisol in Cyprinus carpio.

Bioaccumulation of lead nitrate in freshwater crayfish (Astacus leptodactylus) tissues under aquaculture conditions.

The aim of this research was to evaluate the amount of lead in the tissue of Astacus leptodactylus especially in their muscle which the consumed part of their body. In this study the crayfish was exposed to intermediate concentration of lead nitrate (500 microg L(-1)) for periods up to 3 weeks. In the first, second and third weeks bioaccumulation in various tissues was under investigation. The data of toxicological analysis obtained by the method of atomic absorption revealed that the levels of bioaccumulation of metal are different in various tissues of this crayfish. The accumulation of the lead in gills was the highest and in muscles was lowest degree. The amount of heavy metals in the tissues of crayfish was as follow. Gills>exoskeleton>hepatopancreas (digestive glands)>digestive tract>green gland>testis and ovary>muscles.

Effects of copper sulfate (CuSO4) on the levels of glucose and cortisol in common carp, Cyprinus carpio.

The objective of this study was to evaluate the possible effects of CuSO4 exposure on variations of glucose and cortisol levels in Cyprinus carpio. Three replicates of 6 fish were subjected to two sub-lethal concentrations of CuSO4 (0.16 and 0.53 mg L(-1)) for 14 and 21 days. Blood samples were isolated from the fish following the exposure, to measure the levels of cortisol and glucose compared to the control group. The results showed significant increases (p < 0.05) in cortisol levels for both fish groups after 14 days of exposure, whereas, the levels of blood cortisol in both groups did not differ from that of control when the fish subjected to copper sulfate for 21 days. We found significant increases (p < 0.05) in the levels of blood glucose of two groups of fish after 14 days of exposure to two doses of CuSO4, as well as significant decrease in the blood glucose of both groups exposed for 21 days. In the later treatment, the rate of decrease in group II (exposed to 0.53 mg L(-1) CuSO4) was higher than that of group I (exposed to 0.16 mg L(-1) CuSO4) (p = 0.001 compared to p = 0.032). Our findings attest that exposing to waterborne copper would affect the levels of both cortisol and glucose, as indicators of stress response in Cyprinus carpio.