Testis Injury Research Articles

Investigation of the Effects of Artemisinin on Testis and Kidney Injury Induced by Doxorubicin

Abstract Artemisinin, an antimalarial drug, has anticancer activity and possesses protective effects against several tissue injuries. The aim of the present study was to investigate the effects of artemisinin on doxorubicin-induced renal and testicular toxicity in rats. Doxorubicin was administered to rats at a single dose of 10 mg/kg body weight (b.w.) as a single intraperitoneal injection. Application of artemisinin was by using oral gavage feeding needle for 14 days at different specified doses (7 mg/kg and 35 mg/kg b.w.). At the end of the experiments, kidney and testis samples were collected and used for histopathological and immunohistochemical examinations. At histopathological examination, while hyperemia was the marked finding in kidney and testis of rats treated with doxorubicin only, no evidence of structural abnormalities showed in other groups. Immunohistochemical examination of the testes and kidneys demonstrated significantly increased expression of caspase-3, TNF-α, iNOS and NF-κB in rats treated with doxorubicin only. Artemisinin decreased the doxorubicin-induced overexpression of NF-κB, iNOS, TNFα and caspase-3 in these tissues of rats. Artemisinin can protect the kidney and testis against doxorubicin-induced nephrotoxicity and testotoxicity, probably through a decrease of caspase-3, TNF-α, iNOS and NF-κB expressions. It may be concluded that artemisinin has a potential for clinical use in the treatment of kidney and testis damage induced by doxorubicin. Further researches are required to determine the appropriate combination of artemisinin with doxorubicin.

Mechanism of cadmium poisoning on testicular injury in mice.

Cadmium is a heavy metal that is toxic to humans and the reproductive system. The present study aimed to investigate the mechanisms of cadmium-induced reproductive toxicity in a male Institute of Cancer Research mouse model of cadmium poisoning. Changes in luteinizing hormone receptor (LHR), 17α-hydroxylase and endothelial nitric oxide (NO) synthase (eNOS) expression levels were examined. A total of 24 male mice (4-week-old) were randomly divided into four groups (normal control group and low, medium and high cadmium groups) and subjected to gavage treatment with normal saline or cadmium-containing saline solutions for 8 weeks prior to sacrifice. To assess testicular injury, serum androgen levels were determined by ELISA, testicular tissue pathological changes were evaluated using hematoxylin and eosin staining. In addition, LHR, 17α-hydroxylase and eNOS expressions levels were examined by western blotting, and apoptosis was examined with a terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The results demonstrated that the severity of testes injury increased with cadmium concentration. In addition, LHR, 17α-hydroxylase and eNOS expression levels increased with low and medium concentrations of cadmium; however, they were decreased following treatment with high concentrations of cadmium. The results from the present study demonstrated that cadmium altered LHR, 17α-hydroxylase and eNOS expression levels in testicular stromal cells, which may impact testosterone synthesis. Furthermore, NO was suggested to be involved in cadmium-induced testicular injury by measurements of eNOS expression in testicular stromal cells.

Treatment with melatonin and selenium attenuates docetaxel-induced apoptosis and oxidative injury in kidney and testes of mice.

Docetaxel (DTX) has been used in cancer treatments for several decades, but it results in many adverse apoptotic effects through excessive production of reactive oxygen species (ROS) in some tissue including the kidney and testes. We aimed to investigate potential modulatory roles of melatonin (MEL) and selenium (Se) against DTX-induced apoptosis and oxidative injury in the testes and kidney of mice. Thirty-two mice were divided into four equal groups as control, DTX, DTX+MEL and DTX+Se. DTX group was treated with a single intraperitoneal dose of DTX. After DTX treatment, MEL and Se were administered to the mice in the DTX+MEL and DTX+Se groups for 7days respectively. Increased lipid peroxidation, ROS, apoptosis, caspase-3 and caspase-9 activities in the kidney and testes of the DTX group were diminished by treatment with MEL and Se. DTX-induced decreases in vitamin E (α- and γ-tocopherol), glutathione peroxidase and reduced glutathione levels in the kidney and testis were increased following MEL and Se treatments. In conclusion, our data show that MEL and Se can act as modulators against DTX-induced apoptosis and oxidative damage in the kidney and testis through up-regulation of glutathione and vitamin E and down-regulation of caspase pathways.

TGF-β mediates thoracic radiation-induced abscopal effects of testis injury in rat

To investigate the thoracic irradiation induced abscopal effect on distal testes and the underlying inflammatory factors, the rats were irradiated on right thorax with fractionated doses. It was found the testes structures were damaged including disorder of spermatogenic cell arrangement and decrease of sperm number. Moreover, the expressions of caspase-3 and caspase-8 in testis tissue were enhanced, and the concentrations of TGF-β and TNF-α in the rat serum were increased. When TM4 cells were treated with the conditioned medium (CS) collected from irradiated rat, the cellular ROS and apoptosis was significantly increased. When the CS was neutralized with anti-TGF-β, its toxic effects were reduced. These results suggest that the thoracic irradiation-induced TGF-β was involved in the above abscopal damage of testes, which reinforces the necessity of new prevention strategy development of radiotherapy in avoiding any abnormal genetic consequence.

Nasturtium Officinale L. hydroalcoholic extract improved oxymetholone-induced oxidative injury in mouse testis and sperm parameters.

Testicular tissue and sex hormones are sensitive to the anabolic steroids (oxymetholone/OM) due to increased free radical damage and hormonal changes. The Nasturtium officinale L. have various antioxidant compounds. The aim of the present study was to investigate N.officinale effect on OM-induced oxidative injury in mouse testis and sperm parameters. Thirty BALB/c mice were divided into five groups, including control, OM (5ml/kg) and three N.officinale doses (25, 50 and 100mg/kg)+OM. At the end of the study (40days), serum luteinising hormone (LH), follicle-stimulating hormone (FSH), testosterone, nitric oxide (NO) levels, ferric reducing ability of power (FRAP) and testis stereological factors were measured. The sperm parameters were evaluated. Liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI/MS) analysis was yielded a fingerprint of N.officinale phenolic constituents. 100mg/kg of N.officinale extract significantly reduced the serum level of testosterone and a significant increase in LH and FSH in comparison with the control group. This dose also significantly improved the stereological factors and sperm parameters. 50 and 100mg/kg of N.officinale extract significantly increased the testis tissue FRAP levels, and 100 doses reduced the serum levels of NO. Fourteen compounds and 34 peaks were identified in the extract with LC-ESI/MS. Nasturtium officinale extract has protective effects against testicular toxicity caused by OM.

Luteolin Ameliorates Testis Injury and Blood-Testis Barrier Disruption through the Nrf2 Signaling Pathway and by Upregulating Cx43.

Luteolin, a natural flavonoid, displays protective activities to testicular tissue. However, the molecular mechanisms are still unclear. In this study, the aim is to identify the protective effects and underlying mechanisms of luteolin against triptolide (TP)-induced damage of testicular tissue. Pre-incubation of Sertoli cells (SCs) with luteolin results in a significant reduction of TP-induced apoptotic cells, which occurs concomitantly with the effective inhibition of reactive oxygen species accumulation. Luteolin results in a significant reduction in testicular damage and spermatogenesis dysfunction in a mouse model of testicular damage. Mechanistic studies reveal that luteolin significantly triggers Nrf2 translocation, increases antioxidant response element-luciferase reporter activity, and induces antioxidant enzyme expression. Nrf2 siRNA reduces luteolin-induced protection in SCs. Besides inhibiting apoptosis, luteolin recovers the blood-testis barrier (BTB) integrity by upregulating connexin43 (Cx43) expression. Moreover, specifically blocked Cx43 activity completely blocks repairmen of luteolin to BTB values. In accordance with in vitro results, luteolin suppresses testicular injury and spermatogenesis dysfunction by activation of Nrf2 and Cx43 in a testicular injury model. Luteolin is identified as a novel active ingredient that contributes to the protective activity in testicular damage through activating the Nrf2 signaling pathway and by upregulating Cx43.

MitoQ ameliorates testis injury from oxidative attack by repairing mitochondria and promoting the Keap1-Nrf2 pathway

Mitochondrial dysfunctions induced by oxidative stress could play a pivotal role in the development of testicular damage and degeneration, leading to impaired fertility in adulthood. MitoQ as mitochondria-targeted antioxidant has been used in many diseases for a long time, but its therapeutic effects on testicular injury ‘have not been reported yet. Here, we examined the protective action mechanism of MitoQ on testicular injury from oxidative stress induced by triptolide (TP). Mice were orally administrated with MitoQ (1.3, 2.6 and 5 .2mg/kg, respectively) in a TP-induced model of testicular damage for 14 days. And then testis injuries were comprehensively evaluated in terms of morphological changes, spermatogenesis assessment, blood-testis barrier (BTB) integrity, and apoptosis. The results demonstrated MitoQ effectively increased testicular weight, maintained the integrity of BTB, protected microstructure of testicular tissue and sperm morphology by inhibition of oxidative stress. Further mechanism studies revealed that MitoQ markedly activates the Keap1-Nrf2 antioxidative defense system characterized by increasing the expression of Nrf2 and its target genes HO-1 and NQO1. Meanwhile, MitoQ upregulated the expression of mitochondrial dynamics proteins Mfn2 and Drp-1and exerted a protective effect on mitochondria. On this basis, the results from pharmacokinetic study indicated that the MitoQ could enter into testis tissues after oral administration in despite of the low absolute bioavailability, which provided the material basis for MitoQ in the treatment of testicular damage. More importantly, MitoQ reached mitochondria quickly and had an outstanding feature of mitochondria targeting in Sertoli cells. Therefore, these results provide information for the application of MitoQ against testicular injury diseases.

Treatment with estrogen receptor agonist ERβ improves torsion-induced oxidative testis injury in rats

AimsThe purpose of the present study was to investigate the potential antioxidant, anti-apoptotic and sperm function-preserving effects of estrogen, estrogen receptor (ER)α and ERβ agonists in a rat model of testis torsion-detorsion (T/D). Main methodsUnder anesthesia, 6–8-week-old male Sprague-Dawley rats underwent sham-operation or testicular torsion by fixing left testis rotated at 720° for 2 h. After detorsion, rats were treated with ERα agonist (1 mg/kg/day, subcutaneously, sc) or ERβ agonist (1 mg/kg/day, sc) or estradiol (E2, 1 mg/kg/day, in drinking water) or vehicle on the following two days. On the third day, testicular blood-flow was recorded and then left testes were extracted for molecular and histochemical analysis. Key findingsThe findings showed that reduced testicular blood-flow following torsion was partially restored on the 3rd day of detorsion, while treatments with either of the ER agonists or E2 returned blood flow fully back to the control levels. When the testis-torsioned rats were given ERβ agonist during the detorsion period, tubular injury was lessened, sperm count and motility were increased, while the production of reactive oxygen metabolites and apoptosis in the testis tissues were totally suppressed. Although a down-regulated expression of androgen receptor (AR) along with a reduction in serum testosterone level was observed in the vehicle-treated T/D group, all three treatments up-regulated the expressions of AR and its mRNA, while ERα agonist and E2 suppressed the testosterone level. SignificanceERβ receptor activation during the post-ischemic period may be beneficial in protection against torsion-related oxidant testicular injury and infertility.

Experimental study on prophylactic effects of vardenafil in ischemia–reperfusion model with intestinal volvulus injury in rats

AimAn experimental study was performed to evaluate the effects of Vardenafil on ischemia–reperfusion (I/R) injury in an experimental volvulus model by histochemical and biochemical methods. Materials and methodsThirty-five male Wistar rats were divided in five groups (n = 7). In Group 1, a 5 cm segment of small intestine 2 cm proximal to cecum was excised to have a control group. In the second group, 5 cm segment of small intestine 2 cm proximal to cecum was rotated 360° clockwise direction and sutured with 4/0 polyglactin to generate an experimental model of volvulus. At the end of 2 h of ischemia, the same intestinal segment was sampled. In group 3, after achieving ischemia similar to group 2, two hours of reperfusion injury was obtained by removing the sutures. Rats in Group 4 received vardenafil after 1.5 h of ischemia and then 2 h of reperfusion. And finally, in Group 5, vardenafil was administered 2 h before laparotomy and 5 cm of intestine was removed without I/R injury. Intestinal segments were evaluated for total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) with biochemical and histopathological analysis. ResultsSerum TOS levels and OSI were not significantly different between groups (p = 0.910, P = 0,43 respectively). The serum TAS level was decreased in group 3 as compared to vardenafil groups 4 and 5, without a statistical significance (p = 0.428). In histopathologic analysis, we found that vardenafil, partially reduced I/R injury. The villus structure was preserved but, congestion and inflammation were moderate. ConclusionVardenafil partially reduced I/R injury histopathologically on intestine. Our study shows that it does not have statistically antioxidant effect on intestinal I/R injury in experimental model of volvulus. However, effects of vardenafil in I/R injury of liver, kidney, heart, testis, over and brain which were cited in literature were not confirmed with I/R injury on intestine.

Intervention of curcumin and its analogue J7 on oxidative stress injury in testis of type 2 diabetic rats

To investigate the intervention of curcumin and its analogue J7 on oxidative stress injury in testis of type 2 diabetic rats. Sixty male SD rats, 10 rats were chosen as normal control group (NC), the other 50 rats were assigned to experiment group. Experiment diabetic rats were induced by high-fat food and intraperitoneal injection of steptozotocin (STZ). After the model was established successfully, diabetic rats were divided into four groups randomly: diabetes mellitus group (DM, n=12), curcumin treatment group (CUR, n=10), high dose treatment group of J7 (J+, n=10), low dose treatment group of J7 (J-, n=10). The CUR group were intragastrically administered with curcumin 20 mg/kg daily, in addition, the J+ group and the J- group were intragastrically administered with J7 20 mg/kg and 10 mg/kg daily respectively. After 8 weeks, the fast blood glucose was detected biochemically. The activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were detected by hydroxylamine method and thiobarbituric acid method respectively. The protein expressions of the nuclear factor-erythroid 2-related factor 2 (tNrf2), phosphorylation of Nrf2 (pNrf2), catalase (CAT), NAD(P)H quinine oxidoreductase 1 (NQO1) were measured by Western blot. The mRNA expressions of CAT, NQO1, hemeoxygenase-1 (HO1) were measured by quantitative real-time PCR (qRT-PCR). Morphological structure of testis was observed by hematoxylin-eosin (HE) staining. The expressions of Nrf2 and CAT were also detected by immunohistochemical method. The levels of fast blood glucose and MDA in DM group were increased significantly(P＜0.05), while the body weight, the activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of CAT, NQO1, HO1 were decreased (P＜0.05). Under light microscope, the DM group showed disrupted histological appearance. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were decreased. With the treatment of curcumin and J7, the MDA levels in the three treatment groups were decreased (P＜0.05). The activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of NQO1, HO1 were increased (P＜0.05). the levels of fast blood glucose were decreased in the J+ and J- group (P＜0.05), and the mRNA expression of CAT was increased in the J+ group (P＜0.05). The ratio of pNrf2/tNrf2 in the J+ group was significantly higher than that in CUR and J- group (P＜0.05). The protein level of CAT in the J+ group was also significantly higher than that in J- group (P＜0.05). There were no significant differences in other indexes among the three treatment groups. Under light microscope, the morphology was obviously improved in the three treatment groups. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were increased in the three treatment groups. It was suggested that high dose J7 had better antioxidant stress ability in testis of diabetic rats. Curcumin and J7 could inhibit the oxidative stress damage of testicular tissue in diabetic rats, which might be related with the activation of the Nrf2-ARE signaling pathway.

Protective Effect of L-cysteine Against Sodium Valproate-induced Oxidant Injury in Testis of Rats

Protective Effect of L-cysteine Against Sodium Valproate-induced Oxidant Injury in Testis of Rats

The dangers of hurling-genital injuries arising in the modern game.

To assess the proportion of penoscrotal injuries arising from the sport of hurling and to assess work-up and management of each injury. Using Hospital In-Patient Enquiry data, all penoscrotal injuries occurring over a 10-year period between 2007 and 2017 were identified and assessed. Chart review, imaging reports, operative notes and discharge summaries were used to identify the aetiology of each injury and those occurring due to hurling were selected for analysis. Investigations and management of each case were reviewed. Seventy patients presented to our institution over a 10-year period with penoscrotal injuries and, of these, ten patients (14%) presented with injuries arising due to blunt scrotal trauma whilst playing hurling. The average age of these patients was 24.3years, and the right testicle was injured six times, compared with the left testicle twice and isolated scrotal injuries twice also. One hundred percent of patients underwent diagnostic ultrasonography with Doppler flow assessment with 90% (n = 9) having positive findings. Three patients (33%) required operative management with only one patient (10%) requiring an orchidectomy. There were no delayed or interval procedures. Hurling is a physical sport with a notable proportion of blunt scrotal trauma arising due to the sport. Prompt physical examination and diagnostic ultrasonography are essential in investigations of injuries, and surgical exploration should be considered in all cases with concerns of testicular survival. Groin protection should be recommended to all players and in particular to those at high risk such as single testis or prior injury.

Polydatin Alleviates Radiation-Induced Testes Injury by Scavenging ROS and Inhibiting Apoptosis Pathways.

BackgroundExposure to ionizing radiation (IR) induces severe damage in multiple human tissues. The testes are extremely sensitive to IR, and testes irradiation can result in infertility and abnormality. A novel and safe radioprotector for testes injury from IR is needed. Polydatin (PD) has been proved to have anti-oxidant and anti-inflammatory effects, indicating its potential application in radiation protection.Material/MethodsMale wild-type C57BL/6 mice (8 weeks old) were exposed to ionizing radiation. At different times after irradiation, testes were isolated and subjected to hematoxylin-eosin (HE) staining and TUNEL staining, as well as related quantification. ELISA assay was used to measure the level of inflammatory cytokines, and apoptosis proteins were detected by Western blot assay. Intracellular ROS was measured by DCFH-DA flow cytometry method.ResultsIn the present study, we demonstrated that polydatin effectively alleviated testes injury and retained sperm viability. PD pretreatment also inhibited cell apoptosis caused by irradiation. Radiation-induced decrease of FSH and testosterone was also inhibited by PD treatment. Finally, we showed that PD obviously reduced the ROS level, using DCFH-DA method. We also found that PD reduced the concentration of the oxidative products MDA and 8-OHdG. PD also inhibited apoptosis-related proteins such as Bax and caspase 3.ConclusionsOur data proved that polydatin effectively alleviated testes injury after irradiation, mainly through reducing ROS and oxidative stress. Our findings suggest polydatin as a potential radioprotector for testes radiation damage.

Protective effect of N-acetylcysteine on MK-801-induced testicular oxidative stress in mice

Experimental studies indicate that MK-801 causes organ injury in schizophrenic mice testes although it is molecular mechanism has not been clearly defined. In this study, we investigated the probable protective effect of N-Acetylcysteine (NAC) against MK-801- induced testicular toxicity in mice. In total, 24 Balb/C male mice were divided into 4 equal groups: the animals in the control group (vehicle treated) were intraperitoneally given 10 mL/kg/day saline solution, the animals in the experiment groups were intraperitoneally given 1 mg/kg/day MK-801 alone, 100 mg/kg/day NAC alone and MK-801 by 1 mg/kg/day for 14 days. The level of the testes’ total oxidant status (TOS) in mice that were treated with MK-801 was significantly higher than those level in the other groups while the total antioxidant status (TAS) levels decreased. In comparison to the MK-801 group, the TOS levels were lower, and the TAS levels increased in the MK-801 + NAC group. In the morphometric analysis, the diameter and epithelial height of the seminiferous tubules of the testes showed no significant changes after MK-801 administration. Conversely, the weights of the testes decreased significantly. In the treatment with NAC, the weights of testes significantly increased in comparison to the MK-801 group. The histopathological examination revealed necrobiotic and degenerative changes in the epithelial cells, vacuole formation within the seminiferous tubules, a decrease in the number of the spermatozoid, and disorganization in the basement membrane of the seminiferous tubules in the MK-801 group in comparison to the control group. Administration of NAC alleviated several negative effects of MK-801 on the testicular damage in mice. In conclusion, our results showed that NAC protected the mice against the testicular toxicity of MK-801 when it was administrated intraperitoneally.

Cyanidin-3-O-glucoside at Low Doses Protected against 3-Chloro-1,2-propanediol Induced Testis Injury and Improved Spermatogenesis in Male Rats

In recent decades, the capability of mankind spermatogenesis is declining due to various threats. Anthocyanins as colorful polyphenols possess beneficial functions for the organisms, including Leydig cells, but their effects on male spermatogenesis remain underexplored. In our study, the protective effect of cyanidin-3- O-glucoside (C3G) was investigated on the 3-chloro-1,2-propanediol (3-MCPD) caused rat spermatogenic disorders. At low doses, C3G improved the number and motility of the sperms, alleviating the seminiferous tubule injury. Interestingly, C3G showed no influence on sexual hormone but increased the androgen receptor expression. Meanwhile, C3G reduced the oxidative stress and number of apoptotic cells and promoted the integrity of the blood-testis barrier in the testis. Additionally, C3G mediated the activation of p-ERK, p-JNK, and p53, which are related to the protection of Sertoli cells and spermatogenesis. In conclusion, C3G protected against the 3-MCPD caused testis damage and spermatogenic disorders under appropriate doses, which indicates the potential protection of anthocyanins on male reproduction.

Protective Mechanism of Sulforaphane on Cadmium-Induced Sertoli Cell Injury in Mice Testis via Nrf2/ARE Signaling Pathway

The present study evaluated the mechanism underlying the protective effect of sulforaphane (SFN) on cadmium (Cd)-induced Sertoli cell (TM4 cells) injury in mice. The apoptosis rate of cells in each group was detected by flow cytometry. It was determined the effect of SFN on the expression of downstream molecular targets of Nrf2/ARE axis and on the lipid peroxide content. The related genes involved in the nuclear factor E2-related factor 2(Nrf2)/antioxidant response element (ARE) signaling pathway were evaluated by RT-PCR; for example, the mRNA expression levels of Nrf2, heme oxygenase-1 (HO-1), glutathione peroxidase (GSH-Px), quinone oxidoreductase 1 (NQO1), and γ-glutamylcysteine synthetase (γ-GCS), while the protein expression levels were assessed by Western blot. Our results showed that the mRNA and protein expression levels of Nrf2, HO-1, NQO1, GSH-Px, and γ-GCS were increased in various degree when the Sertoli cells were to added different concentrations of SFN. Our results also showed that SFN reduced the apoptosis rate, increased the activity of T-SOD, inhibited the increase of the MDA content caused by Cd. Meanwhile, SFN could increase the mRNA and protein expression levels of Nrf2, HO-1 and NQO1 and reduced the mRNA and protein expression levels of GSH-Px and γ-GCS caused by Cd in Sertoli cells (p < 0.01). Taken together, SFN could improve the antioxidant capacity of Sertoli cells, and exert a protective effect on the oxidative damage and apoptosis of Cd-induced Sertoli cells through the activation of Nrf2/ARE signal transduction pathway.

Protective effects of camel whey protein against scrotal heat-mediated damage and infertility in the mouse testis through YAP/Nrf2 and PPAR-gamma signaling pathways.

Elevation of scrotal temperature is one of the most important causes of impaired spermatogenesis and male infertility, but the exact mechanism remains controversial. The present study investigated the impact of camel whey protein (CWP) on the mechanisms of heat stress (HS)-mediated testicular damage in male mice. Exposure to HS was associated with significant increase in the testicular tissues' oxidative stress. Mechanistically, exposure to HS resulted in upregulation of P53 and Nrf2 expressions; downregulation of Bcl2 and PPAR-γ expressions; and induction of testicular Leydig cell hyperplasia. Because Leydig cells produce testosterone up on stimulation with Luteinizing hormone (LH), HS mice also exhibited significant reduction in the serum testosterone levels followed by significant reduction in the percentages of progressively motile sperm and higher percentages of immotile sperm, when compared with those of control mice. Interestingly, treatment of HS mice with CWP significantly restored the levels of ROS and the activities of antioxidant enzymes in the testicular tissues nearly to those observed in control mice. Furthermore, CWP supplemented HS mice exhibited complete restoration of Bcl2, P53, Nrf2, and PPAR-γ expressions; testicular Leydig cell distribution; significant higher levels of testosterone levels; and hence higher percentages of progressively motile sperm and lower percentages of immotile sperm as compared to HS mice. Our findings reveal the protective effects of CWP against testis injury and infertility induced by exposure to HS by rescuing functional Leydig cells. Additionally, the present study has shed light on the molecular mechanisms underlying improved testicular damage following CWP treatment.

Effects of oral cimetidine on the reproductive system of male rats.

Cimetidine is widely used for the treatment of digestive tract ulcers, but it induces testis injury. To explore the mechanisms underlying cimetidine-induced toxicity towards the testis, the effects of oral cimetidine on the reproductive system of male rats were assessed. Cimetidine was orally administered to male rats at 20, 40 or 120 mg/kg/day for 9 weeks. The rats were then euthanized, and serum, testis, epididymis, prostate gland, seminal vesicle, preputial gland, levator ani muscle and sphincter ani samples were collected. Sperm parameters were obtained by computer-assisted sperm analysis. Serum hormone levels were measured by ELISA. Protein expression levels were detected by immunohistochemistry. Apoptosis was assessed with the DeadEnd™ Colorimetric Apoptosis Detection System. The results indicated that the sperm average path velocity, straight line velocity and curvilinear velocity were significantly decreased in the 120 mg/kg cimetidine group compared with the control group, while luteinizing hormone and testosterone levels were significantly higher compared with the control group. Testicular lesions were observed by histopathology in the 120 mg/kg cimetidine group. The amounts of cells positive for cyclooxygenase-2 (COX-2) and nuclear factor κB (NF-κB) were increased in the 120 mg/kg cimetidine group compared with the control group. The amounts of cells positive for iNOS were increased in all cimetidine treatment groups. In addition, apoptotic cells were significantly more abundant in the 120 mg/kg cimetidine group compared with the control group, as indicated by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling. Overall, 9 weeks of oral cimetidine induced pathological changes in the testicles and hormone secretion disorder in rats. COX-2, iNOS and NF-κB upregulation and induction of apoptosis may be associated with the reproductive toxicity caused by cimetidine.

Protective effects of amifostine, curcumin and caffeic acid phenethyl ester against cisplatin-induced testis tissue damage in rats.

Cisplatin is an effective antineoplastic drug that is usually used to treat a number of different types of cancer in the clinic. One of the most notable side effects of cisplatin use is infertility. The present study was designed to determine the non-oxidative testicular effects caused by the use of cisplatin in rats. The rats were randomly allocated to the experimental groups. The untreated rats represented the control group (group I) and the treatment groups were as follows: cisplatin alone (group II), cisplatin+amifostine (group III), cisplatin+curcumin (group IV), and cisplatin+caffeic acid phenethyl ester (CAPE; group V). The present study observed that following cisplatin administration, the expression of nuclear factor-κB (NF-κβ)/p65, caspase-3 and 8-deoxyguanosine (8-OHdG) increased in germinal epithelium and Leydig cells. However, the expression of these markers decreased in groups III–V, most notably in the group treated with amifostine. cisplatin induced-damage was countered by amifostine and curcumin. The results revealed that the activation of NF-κB, caspase-3 and 8-OHdG had a significant role in cisplatin-induced testicular toxicity. Thus, amifostine, curcumin and, to a lesser extent, CAPE have the potential for use as therapeutic adjuvants in cisplatin-induced testis injury.

Rosemary extract modulates fertility potential, DNA fragmentation, injury, KI67 and P53 alterations induced by etoposide in rat testes

Etoposide is a semi-synthetic compound derived from the plant podophyllum pelltatum and are antineoplastic agents long been used for treatment of human malignancies. The present study was conducted to examine the possible modifying effects of rosemary aqueous extract against sperm abnormalities, testes injury, DNA fragmentation, apoptosis and Ki67 alterations induced by Etoposide in male rats. A total of 50 adult male rats were divided into 5 groups (1st, control; 2nd, rosemary; 3rd, Etoposide; 4th, co-treated Etoposide with rosemary; 5th, post-treated Etoposide with rosemary). Sperms counts, motility and viability and KI67 immunoreactivity in testes were significantly decreased while; sperm abnormalities, testicular injury, P53 and DNA damage were a significantly increased in Etoposide group as compared to control group. Co-administration of rosemary with Etoposide improved the sexual toxicity, fertility potential, testicular injury, KI67, P53 and DNA damage induced by Etoposide. Etoposide treatment induced depletion in counts, motility and viability of rat sperms. Etoposide treatment induced testicular DNA damage, injury and decreased in KI67 and P53 expressions. Treatment with rosemary with Etoposide improved these alterations.