The therapeutic effect of hesperetin on doxorubicin-induced testicular toxicity: Potential roles of the mechanistic target of rapamycin kinase (mTOR) and dynamin-related protein 1 (DRP1).

Clinical utilization of doxorubicin (DOX), which is a commonly used chemotherapeutic, is restricted due to toxic effects on various tissues. Using hesperetin (HST), an antioxidant used in Chinese traditional medicine protects testis against DOX-induced toxicity although the molecular mechanisms are not well-known. The study was aimed to examine the possible role of the mechanistic target of rapamycin kinase (mTOR) and dynamin 1-like dynamin-related protein 1 (DRP1) in the therapeutic effects of HST on the DOX-induced testicular toxicity. Rats were divided into Control, DOX, DOX + HST, and HST groups (n = 7). Single-dose DOX (15 mg/kg) was administered intraperitoneally and HST (50 mg/kg) was administered by oral gavage every other day for 28 days. Total antioxidant status (TAS), histopathological evaluations, immunohistochemistry, and gene expression level detection analyses were performed. Histopathologically, DOX-induced testicular damage was ameliorated by HST treatment. DOX reduced testicular TAS levels and increased oxidative stress markers, 8-Hydroxy-deoxyguanosine (8-OHdG), and 4-Hydroxynonenal (4-HNE). Also, upregulated mTOR and DRP1 expressions with DOX exposure were decreased after HST treatment in the testis (p < 0.05). On the other hand, DOX-administration downregulated miR-150-5p and miR-181b-2-3p miRNAs, targeting mTOR and mRNA levels of beclin 1 (BECN1) and autophagy-related 5 (ATG5), autophagic markers. Furthermore, these levels were nearly similar to control testis samples in the DOX + HST group (p < 0.05). The study demonstrated that HST may have a therapeutic effect on DOX-induced testicular toxicity by removing reactive oxygen species (ROS) and by modulating the mTOR and DRP1 expressions, which have a critical role in regulating the balance of generation/elimination of ROS.

Caffeine versus antioxidant combination (Antox) and their role in modifying cadmium-induced testicular injury in adult male albino rats.

The aim of the current work was to compare the roles of caffeine and antioxidants in prevention of cadmium-induced testicular damage when given, in addition to cadmium, in adult male albino rats. Histopathological and ultra-structural examination as well as biochemical and molecular assessments were done. Cadmium chloride (4 mg/kg body weight) was administered via oral gavage from day 21 to 28 of the experiment. Caffeine (25 mg/kg) via intra-peritoneal injection and antioxidant preparation (Antox) 10 mg/kg via oral gavage were given as a pre-treatment for 21 days and concomitantly with Cd from day 21 to 28. Real-time PCR was done for determination of 3, 17 ß hydroxy steroid dehydrogenase steroidogenic acute regulatory protein, caspase-9 and mitofusin 1,2 gene expression. Testosterone level, glutathione S-transferase enzyme activity, reactive oxygen species, malondialdehyde and superoxide dismutase were measured spectrophotometrically by ELISA. Histological and ultra-structural evaluation revealed disturbance of normal architecture, vacuolisation and necrosis. Vascular dilatation and congestion and collagen fibre deposition were present. A statistically significant difference was seen in all parameters when caffeine and antioxidants were given against cadmium-induced testicular injury. Overall, we conclude that both caffeine and antioxidants have the ability to reverse cadmium-induced testicular injury when given as pre-treatment prior to cadmium exposure.

Protective and therapeutic effect of hydrogen sulfide on hemorrhagic cystitis and testis dysfunction induced with cyclophosphamide

Backround/aim: Cyclophosphamide (CP) is a drug used for treatment of many malignant diseases. However, it can cause serious side effects such as hemorrhagic cystitis and male infertility. Hydrogen sulfide (H2S) is a gaseous mediator and is suggested to have antioxidant, antiinflammatory, and antiapoptotic effects. In this study, dose-dependent effects of H2S donor sodium hydrosulfide (NaHS) on cyclophosphamide-induced hemorrhagic cystitis and testicular dysfunction were investigated in rats. Material and methods: Rats were divided into 5 groups (n = 8): control, CP, NaHS25 µmol/kg, NaHS50 µmol/kg, and NaHS100 µmol/ kg. After treatment for 7 days intraperitoneally (ip), a single ip dose of CP 200 mg/kg was given on the 8th day. Then, treatment was continued for 7 days. In bladder and testicular tissues, IL 6, IL 10, cGMP, NO, H2S, FSH, LH, and testosterone levels were measured by ELISA. Histopathological examination with H&E staining, as well as immunohistochemical staining for acrolein in bladder and caspase-3 and APAF-1 in testis were performed. Results: NaHS prevented the increased IL 6 and IL 10 values induced by CP as well as prevented the decrease in cGMP values associated with CP. There was no significant change in FSH values, but the LH value, which increased with CP, decreased with 25, 50, and 100 µmol/kg NaHS. In contrast, testosterone decreased in the CP group and increased in the treatment groups. NaHS was effective in many biochemical and histopathological parameters at 25 and 50 µmol/kg doses, and this effect decreased at 100 µmol/kg dose. Conclusion: H2S has a protective and therapeutic effect on hemorrhagic cystitis and testicular dysfunction induced by cyclophosphamide. It can be suggested that H2S is a promising molecule in facilitating cancer treatment.

Therapeutic prospects of hydroxytyrosol on experimentally induced diabetic testicular damage: potential interplay with AMPK expression.

Male reproductive dysfunction represents one of the overlooked consequences of diabetes that still deserve more scientific attention. We designed this study to explore the therapeutic potential of hydroxytyrosol (HT) on diabetic testicular damage and to investigate its relationship with adenosine monophosphate-activated protein kinase (AMPK) expression. In this context, 30 adult male Wistar rats were utilized and subdivided into control, diabetic and HT-treated diabetic groups. Testicular sections were prepared for histopathological examination and immunohistochemical detection of 8-hydroxy-2'-deoxyguanosine, Sertoli cell vimentin, myoid cell α-SMA, androgen receptors and caspase-3. We also assessed oxidative enzymatic and lipid peroxidation biochemical profiles, sperm count, morphology and motility. Real-time PCR of AMPK expression in tissue homogenate was performed. We observed that HT restored testicular histopathological structure and significantly reduced oxidative DNA damage and the apoptotic index. The HT-treated group also exhibited significantly higher Sertoli cell vimentin, myoid cell α-SMA and androgen receptor immune expression than the diabetic group. A rescue of the oxidative enzymatic activity, lipid peroxidation profiles, sperm count, morphology and motility to control levels was also evident in the HT-treated group. Significant upregulation of AMPK mRNA expression in the HT-treated group clarified the role of AMPK as an underlying molecular interface of the ameliorative effects of HT. We concluded that HT exhibited tangible antioxidant and antiapoptotic impacts on the testicular cytomorphological and immunohistochemical effects of experimentally induced diabetes. Furthermore, AMPK has an impactful role in the molecular machinery of these effects.

Nitroglycerin ameliorates sperm parameters, oxidative stress and testicular injury following by testicular torsion/detorsion in male rats.

PURPOSE: This study was designed to determine the probable protection mechanisms of nitroglycerin, a widely used medication for treatment of heart failure and angina, in amelioration of testicular ischemia/reperfusion damage. METHODS: 24 adult male rats were randomly divided into three equal groups; with eight rats in each group: Group 1 (Sham) was sham-operated. Group 2 (T_D): 2 h testicular torsion was induced, afterward detorsion was performed and maintained for 2 h. Group 3 (NG): Nitroglycerin was administered immediately after detorsion. Sperm quality parameters such as viability, motility, morphology, and concentration, levels of antioxidant enzymes (glutathione peroxidase (GPX), catalase (CAT), and total antioxidant capacity (TAC)), and amount of malondialdehyde (MDA) in the blood plasma were examined in each group, thereafter histopathological parameters including germinal epithelial cell thickness (GECT), mean seminiferous tubular diameter (MSTD), Johnson's score and Cosentino's score were assessed. RESULTS: Testicular T_D significantly reduced sperm viability, motility, and normal morphology, whereas the NG administration remarkably increased the percentage of live, motile, and normal spermatozoa (p < 0.05). Levels of GPx, CAT, and TAC significantly reduced and the MDA level significantly increased in the T_D group in comparison to the sham group (p < 0.05). The NG treated group demonstrated significantly reduced MDA concentrations as well as elevated levels of GPx and CAT compared to the T_D group (p < 0.05). Induction of testicular torsion significantly reduced Johnson's score, GESCT (µm), and MSTD (µm), and remarkably increased the Cosentino's score (P < 0.05), while NG injection significantly increased Johnson's score, GESCT (µm), and MSTD (µm) and reduced the Cosentino's score (P < 0.05). CONCLUSION: According to the findings in this research, nitroglycerin was able to protect the testicular tissue from ischemia-reperfusion damage caused by induced torsion/detorsion.

Modulation of reproductive dysfunctions associated with streptozocin-induced diabetes by Artemisia judaica extract in rats fed a high-fat diet.

We investigated the palliative effect of Artemisia judaica extract (AjE) on testicular deterioration induced by DM in high-fat diet/streptozocin (HFD/STZ)-injected rats. Forty rats were allocated to the following five groups: control, AjE, HFD/STZ, HFD/STZ-AjE, and HFD/STZ-metformin. HFD/STZ-diabetic rats showed a marked decrease in testicular weight and male sex hormones. There was significant suppression of testicular antioxidant enzymes and glutathione content in HFD/STZ-diabetic rats. However, rats that had received the STZ injection and the high-fat diet displayed increased malondialdehyde content and nitric oxide levels as well as tumour necrosis factor-alpha. High levels of Bax and low levels of Bcl-2 were detected after the STZ injection. Obvious pathological alterations were found in the testicular tissue of the HFD/STZ-diabetic rats. Thus, the administration of AjE attenuated the biochemical, molecular, and histopathological changes in the testes of the diabetic rats. The obtained findings showed that AjE treatment attenuated the diabetes-induced reprotoxicity in male rats via its antioxidant, anti-inflammatory, and antiapoptotic properties.

Can troxerutin pretreatment prevent testicular complications in prepubertal diabetic male rats?

OBJECTIVE: The vast majority of type 1 diabetes leads to a higher prevalence of reproductive system's impairments. Troxerutin has attracted much attention owing to its favorable properties, including antihyperglycemic, anti-inflammatory, and antiapoptotic effects. This investigation was proposed to evaluate whether pretreatment with troxerutin could prevent apoptosis-induced testicular disorders in prepubertal diabetic rats. METHODS: Fifty prepubertal male Wistar rats were randomly allocated into five groups: control (C), troxerutin (TX), diabetic (D), diabetic+troxerutin (DTX), and diabetic+insulin (DI). Diabetes was induced by 55 mg/kg of streptozotocin applied intraperitoneally. In TX and DTX groups, 150 mg/kg troxerutin was administered by oral gavage. Diabetic rats in DI group received 2-4 U NPH insulin subcutaneously. Troxerutin and insulin treatments were begun immediately on the day of diabetes confirmation. After 30 days, the testicular lipid peroxidation and antioxidant activity, apoptosis process, and stereology as well as serum glucose and insulin levels were assessed. RESULTS: The results showed that diabetes caused a significant increase in the blood glucose, the number of TUNEL positive cells and tubules, and the malondialdehyde level as well as a significant decrease in serum insulin level compared to controls. The stereological analysis also revealed various alterations in diabetic rats compared to controls. Troxerutin treatment improved these alterations compared to the diabetic group. CONCLUSION: Troxerutin-pretreatment may play an essential role in the management of the type-1 diabetes-induced testicular disorders by decreasing blood glucose and modulating apoptosis.

Research on the protective effect of caffeic acid phenethyl ester on testicular damage caused by cisplatin

Background/aim: Cisplatin (CP), a chemotherapeutic drug, causes damage to spermatogenic serial cells, Sertoli cells, and Leydig cells in rat testicles. It was aimed to investigate the protective effect of caffeic acid phenethyl ester (CAPE), one of the active ingredients of propolis, in eliminating CP-induced testicular damage. Materials and methods: Group 1 (control group) was given physiological saline solution intraperitoneally (IP) throughout the experiment. Group 2 (CP group) was given a single dose of CP (7 mg/kg) IP on the day 7. Group 3 (CP + CAPE group), was given CAPE (10 µmol/kg/day) IP for 12 days and a single dose of CP (7 mg/kg) IP on day 7. Group 4 (CAPE group) was given CAPE (10 µmol/kg/day) IP for 12 days. On day 14 of the experiment, the rats were decapitated under xylazine and ketamine anesthesia and their testicles were removed. The sections obtained from the testicles were stained with hematoxylin-eosin and histopathological damage was evaluated. Malondialdehyde (MDA) levels, and superoxide dismutase (SOD) and catalase (CAT) enzymatic activities were measured in the testicular tissue samples. Testosterone (TES) levels were measured in the blood serum. The Johnsen testicular biopsy score (JTBS) was used to evaluate testicular tubules. DNA damage was evaluated in sperm samples taken from the ductus epididymis using the comet assay technique. Results: In Group 2, which was given CP, the testicles were severely damaged.It was observed that histological damage was reduced in the testes by administering CAPE in Group 3. Moreover, according to the JTBS, the value was significantly higher in the testicular tubules (P < 0.05). Moreover, the MDA level decreased in Group 3. However, the SOD, CAT, and TES levels increased in Group 3. DNA damage also decreased significantly in Group 3 when compared to Group 2 (P < 0.05). Conclusion: The results showed that CAPE may be protective against damage caused by CP in the testicles of rats.

Effects of N-nitro L-arginine methyl ester and α-tocopherol on testicular oxidative stress caused by exposure to cigarette smoke.

Testis is a rich organ with blood vessels. For this reason, it is possible that the toxic substances of the cigarette carried in the blood change the balance between the oxidant and the antioxidant system in this organ. In this study, it was aimed to investigate the effects of N-nitro L-arginine methyl ester and α-tocopherol on testicular oxidative stress caused by exposure to cigarette smoke. 45 wistar male rats were used in the study. Five groups were formed: control, cigarette smoke, cigarette smoke + α-tocopherol, cigarette smoke + N-nitro L-arginine methyl ester and cigarette smoke + α-tocopherol + N-nitro L-arginine methyl ester. Biochemical and histological evaluations were performed to determine the damage caused by cigarette smoke. It was observed that there were structural and functional disturbances at the cellular and hormonal level in the smoking group. Biochemical evaluations showed that cellular damage was reduced in treatment groups. Histological examinations were revealed that the damage caused by cigarette smoke exposure was eliminated in treatment groups. As a result of our study, we think that oxidative damage and hormonal irregularity in the testes tissue caused by cigarette smoke exposure can be improved with α-tocopherol and N-nitro L-arginine methyl ester application.

High dose of standardised extract of Costus afer leaves potentiates cadmium reproductive toxicity in Wistar rats.

Protective effects of standardised extract of Costus afer leaves (CAME), an extract with good antioxidants on cadmium-induced reproductive toxicity in male rats, were investigated in this study. Forty-two adult male Wistar rats were randomly divided into six groups and were treated every day regularly for 4 weeks. G1 (control) rats received 1 ml of vehicle treatment. G2 rats were intoxicated with 2.5 mg kg-1  day-1 s.c cadmium chloride for 1 week. G3 and G4 rats were intoxicated with cadmium as in G2 rats and were treated orally with 100 and 200 mg/kg bwt/day of CAME, respectively, for 4 weeks. Group G5 and G6 rats were orally treated with 100 and 200 mg kg-1  day-1 bwt of CAME, respectively, for 4 weeks. Significant changes (p < 0.05) in andrological parameters (sperm count, sperm morphology, serum testosterone and nitric oxide concentration) and testicular antioxidant parameters (reduced glutathione, lipid peroxidation and activities of catalase, glutathione S-transferase and glutathione peroxidase) caused by Cd toxicity were improved in cadmium-intoxicated rats treated with 100 mg/kg body weight of CAME. Administration of 200 mg/kg body weight of CAME to cadmium-intoxicated rats potentiated reproductive toxic effects of cadmium. In conclusion, lower dose of CAME is preferred over high dose in treatment of cadmium-induced reproductive toxicity in rats.

The antiapoptotic and antioxidant effects of eugenol against cisplatin-induced testicular damage in the experimental model.

Testicular dysfunction or damage is among the critical side effects of chemotherapeutic drugs like cisplatin. This study was mapped out to assess the possible therapeutic effect of eugenol on cisplatin-induced testicular damage. In this experimental study, a single dose of cisplatin (15 mg/kg) was given intraperitoneally. After 72 hr of cisplatin injection, rats were sacrificed and testis tissues were removed. Tissues were examined by biochemical, histopathological and immunohistochemical methods. While tissue lipid peroxidation product and apoptotic marker levels increased, antioxidant enzyme activities of testis tissue were decreased in the cisplatin group. Additionally, histopathological damage was also determined in testis tissue. Contrary to all these results, the severity of damage in the tissue was reduced histopathologically owing to eugenol treatment. The lipid peroxidation decreased and antioxidant enzyme activities increased in the eugenol treatment group. It has been determined that eugenol has a therapeutic effect on oxidative stress and apoptosis against cisplatin-induced testicular damage.

Two months sodium nitrate supplementation alleviates testicular injury in streptozotocin-induced diabetic male rats.

NEW FINDINGS: What is the central question of this study? Can low-dose inorganic nitrate supplementation prevent testicular structural and functional alterations in streptozotocin-induced type 1 diabetic male rats? What is the main finding and it's important? Treatment with a low dose of inorganic nitrate for 2 months had protective effects on the male reproductive system in diabetic rats including improved body weight loss, sperm and testis parameters, spermatogenesis index and testicular histology as well as increased serum testosterone levels. These favourable effects may be associated with increased serum insulin and decreased serum glucose, and with modulation of apoptosis in testis. ABSTRACT: Inorganic nitrate supplementation is a possible therapeutic agent in diabetes. The aim of this study was to evaluate the effect of nitrate on the reproductive system in streptozotocin-induced diabetic male rats. Fifty male Wistar rats were allocated randomly to five groups: control (C), control plus nitrate (CN), diabetic (D), diabetic plus insulin (DI) and diabetic plus nitrate (DN). Sodium nitrate was administered for 2 months in the drinking water (100 mg l-1 ) of the CN and DN groups. Insulin was injected at 2-4 U daily in the DI group. Serum glucose level and body weight were measured at the beginning of the study and at regular intervals. At the end of the study, serum levels of glucose, insulin, nitrogen oxides (NOx), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were assessed as well as sperm parameters, testis morphometry and histology, and testicular miR-34b and p53 mRNA expression. Nitrate treatment in diabetic rats significantly improved sperm parameters, epididymal weight, spermatogenesis and testicular histology as well as decreasing serum glucose and testicular p53 gene and miR-34b expression, although it had no effect on serum LH and FSH levels. In diabetic rats, serum insulin and NOx, body weight, testicular and epididymal weight, sperm count and motility, testis morphology, spermatogenesis indices, Johnsen's score, and testosterone were significantly lower than in controls. Nitrate administration increased serum insulin, NOx and testosterone levels in the DN group. Consuming water supplemented with sodium nitrate could improve diabetes-induced testicular functional and structural disorders; these favourable effects may be related to increased serum insulin and decreased serum glucose, as well as modulation of apoptosis in testis.

Amelioration of diabetes-induced testicular and sperm damage in rats by cerium oxide nanoparticle treatment.

Cerium oxide nanoparticles (CNPs) as an antioxidant have been used frequently to attenuate hyperglycaemia oxidative damage in different organs. We investigated the impact CNPs on the qualitative and quantitative sperm parameters, spermatogenesis and NFE2-related factor 2 (Nrf2) expression as a major contributor of antioxidant defence in the male diabetic rats. Twenty-four male rats were divided into four groups. Controls received only mouse food and water. Second group were treated with CNPs (30 mg kg-1  day-1 ) for 2 weeks. Rats in third group received streptozotocin (STZ) (60 mg/kg). In fourth group, animals became diabetic and received CNPs (30 mg kg-1  day-1 ) for 2 weeks. The results showed a significant abnormality in the sperm parameters and histopathological patterns of testes in the diabetic group compared to the control group and CNPs treatment significantly improved all testicular parameters. Following CNPs administration, sperm DNA fragmentation significantly reduced in the STZ-treated rats. Moreover, after CNPs intake in the STZ-treated rats, Nfr2 expression levels increased significantly. Overall, CNPs administration on the diabetic rates can attenuate detrimental effects of diabetes on the sperm potential fertility, sperm parameters, DNA integrity and Nrf2 expression levels. This study gives a future prospect to determine the role of CNPs in the context of diabetes.

Vitamin E improves testicular damage in streptozocin-induced diabetic rats, via increasing vascular endothelial growth factor and poly(ADP-ribose) polymerase-1.

The precise mechanism by which diabetes impairs spermatogenesis and testicular function is not exactly known. Vascular endothelial growth factor (VEGF) and poly(ADP-ribose) polymerase-1 (PARP-1) are important for germ cell homeostasis and repair of DNA respectively. The aim of this study was to investigate the correlation between diabetes-induced testicular damage and testicular VEGF and PARP-1 expression and the possible protective role of vitamin E supplementation. A total of 45 male Wistar albino rats were randomly divided into three groups: Group I (nondiabetic rats), Group II (streptozocin-induced diabetic rats) and Group III (streptozocin-induced diabetic rats treated orally with 0.4 mg/kg vitamin E). Five weeks later, testicular tissue was used for assessment of MDA concentration by colorimetry, histopathological examination and immunostaining for PARP-1 and VEGFIn diabetic rats, testicular weight, seminiferous tubule diameter and germinal epithelial thickness were decreased, basement membrane was thickened and Johnsen score decreased. Reduced VEGF and PARP-1 immunostaining were associated with decreased Johnsen score in diabetic rats. Vitamin E administration was protective against oxidative stress-associated damage evidenced by lower MDA levels, improved testicular weight, spermatogenesis and higher immunostaining for VEGF and PARP-1. Testicular VEGF and PARP-1 might therefore be helpful biomarkers for diabetic testicular damage. Administration of vitamin E may have a protective role against diabetes-induced testicular damage.

Protective effects of the hydroalcoholic extract of Fumaria parviflora on testicular injury induced by torsion/detorsion in adult rats.

This study was designed to determine the effects of daily oral administration (250 mg/kg) of the hydroalcoholic extract of Fumaria parviflora (FP) for 14 days on the sperm parameters, oxidative stress parameters, serum testosterone levels, expression of Bax and Bcl-2 genes, and apoptosis index of germ cells after testicular torsion-detorsion (ischaemia-reperfusion, IR) injury model in rats. Twenty-eight adult male Wistar rats were divided randomly into four groups of seven each: sham operation, torsion-detorsion (TD), TD plus the hydroalcoholic extract FP (TDFP) and only FP without TD application (FP). Testicular torsion was created by rotating the left testis 720° in a counterclockwise direction; then, after 4 hr, detorsion was performed. The Johnson's score, mean seminiferous tubule diameter (MSTD) and height (thickness) of seminiferous tubule epithelium (HST) were significantly increased in TDFP and FP groups as compared to TD group. The gene expression of Bcl-2, level of serum testosterone hormone and antioxidant parameters-GPx and SOD-were significantly higher in TDFP and FP groups than TD group. The index of apoptosis, the gene expression of Bax and the level of MDA were significantly higher in TD group than TDFP and FP groups. Therefore, F. parviflora could decrease oxidative stress induced by testicular torsion-detorsion.

Nano-sized titanium dioxide toxicity in rat prostate and testis: Possible ameliorative effect of morin.

This study investigated the effect of short-term oral exposure to nano-sized titanium dioxide (nTiO2) on Wistar rat prostate and testis, and the associating reproductive-related alterations. The study also evaluated the potential ameliorative effect of the natural flavonoid, morin, on nTiO2-induced aberrations. Intragastric administration of nTiO2 (50mg/kg/day for 1, 2 and 3weeks) increased testicular gamma-glutamyltransferase (γ-GT) activity and decreased testicular steroidogenic acute regulatory protein (StAR) and c-kit gene expression, serum testosterone level and sperm count. nTiO2-treated rats also exhibited prostatic and testicular altered glutathione levels, elevated TNF-α levels, up-regulated Fas, Bax and caspase-3 gene expression, down-regulated Bcl-2 gene expression and enhanced prostatic lipid peroxidation. Sperm malformation and elevated testicular acid phosphatase (ACP) activity and malondialdehyde level, serum prostatic acid phosphatase activity, prostate specific antigen (PSA), gonadotrophin and estradiol levels occurred after the 2 and 3week regimens. Morin (30mg/kg/day administered intragastrically for 5weeks) mitigated nTiO2-induced prostatic and testicular injury as evidenced by lowering serum PSA level, testicular γ-GT and ACP activities and TNF-α level, along with hampering both intrinsic and extrinsic apoptotic pathways. Moreover, morin alleviated prostatic lipid peroxidation, raised prostatic glutathione level, and relieved testicular reductive stress. Additionally, morin increased testicular StAR and c-kit mRNA expression, raised the sperm count, reduced sperm deformities and modified the altered hormone profile. Histopathological evaluation supported the biochemical findings. In conclusion, morin could ameliorate nTiO2-induced prostatic and testicular injury and the corresponding reproductive-related aberrations via redox regulatory, anti-inflammatory and anti-apoptotic mechanisms, promoting steroidogenesis and spermatogenesis, and improving sperm count and morphology.

Effect of Zinc and Melatonin on Oxidative Stress and Serum Inhibin-B Levels in a Rat Testicular Torsion-Detorsion Model.

The present study was aimed to examine the effects of 3-week zinc and melatonin administration on testicular tissue injury and serum Inhibin-B levels caused by unilateral testicular torsion-detorsion in rats. The study was performed on 60 Wistar Albino-type adult male rats. The animals were allocated to 6 groups in equal numbers. 1. Control; 2. Sham; 3. Ischemia-reperfusion; 4. Zinc + ischemia-reperfusion; 5. Melatonin + ischemia-reperfusion; 6. Zinc + melatonin + ischemia-reperfusion. Zinc and melatonin were administered before ischemia-reperfusion at doses of 5 and 3 mg/kg respectively, by intraperitoneal route for a period of 3 weeks. Testicular torsion-detorsion procedures consisted of ischemia for 1 h and then reperfusion for another hour of the left testis. Blood and testicular tissue samples were collected to analyze erythrocyte and tissue GSH and plasma and tissue MDA, Inhibin-B levels. The highest erythrocyte and testis GSH values were found in zinc, melatonin, and zinc + melatonin groups (p < 0.001). Torsion-detorsion group has significantly lower erythrocyte GSH levels and higher plasma MDA values (p < 0.001). Serum inhibin-B and spermatogenic activity levels in the torsion-detorsion group were also significantly lower than those in the other groups (p < 0.001). However, zinc-, melatonin-, and melatonin + zinc-supplemented groups have higher inhibin-B and spermatogenetic activity (p < 0.001). The results of the study show that zinc, melatonin, and melatonin + zinc administration partially restores the increased oxidative stress, as well as the reduced inhibin-B and spermatogenic activity levels in testes ischemia-reperfusion in rats. Suppressed inhibin-B levels in the testicular tissue may be a marker of oxidative stress.

Testicular lymphocytic vasculitis treated with prednisolone and azathioprine.

Testicular vasculitis is a rare condition and little is known about its morphological features. Herein, we report a case of testicular lymphocytic vasculitis, which is rarely documented, in an elderly man. He presented with left testicular swelling and fever, but without any signs of other organ involvement. He was effectively treated with prednisolone and azathioprine. This case report offers information related to the disease course and the importance of biopsy.

Resveratrol and curcumin ameliorate di-(2-ethylhexyl) phthalate induced testicular injury in rats.

The present study aimed to evaluate the protective role of resveratrol and curcumin on oxidative testicular damage induced by di-(2-ethylhexyl) phthalate (DEHP). Male Wistar rats were divided into six groups; three groups received oral daily doses of DEHP (2g/kgBW) for 45days to induce testicular injury. Two of these groups received either resveratrol (80mg/kgBW) or curcumin (200mg/kgBW) orally for 30days before and 45days after DEHP administration. A vehicle-treated control group was also included. Another two groups of rats received either resveratrol or curcumin alone. Oxidative damage was observed by decreased levels of total antioxidant capacity (TAC) and glutathione (GSH) and increased malondialdehyde (MDA) level in the testes of DEHP-administered rats. Serum testosterone level as well as testicular marker enzymes activities; acid and alkaline phosphatases (ACP and ALP) and lactate dehydrogenase (LDH) showed severe declines. DEHP administration caused significant increases in the testicular gene expression levels of Nrf2, HO-1, HSP60, HSP70 and HSP90 as well as a significant decrease in c-Kit protein when compared with the control group. Histopathological observations provided evidence for the biochemical and molecular analysis. These DEHP-induced pathological alterations were attenuated by pretreatment with resveratrol and curcumin. We conclude that DEHP-induced injuries in biochemical, molecular and histological structure of testis were recovered by pretreatment with resveratrol and curcumin. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties along with boosting Nrf2, HSP 60, HSP 70 and HSP 90 gene expression levels and as such may be useful potential tools in combating DEHP-induced testicular dysfunction.

Thymoquinone supplementation ameliorates lead-induced testis function impairment in adult rats.

This study was realized to investigate the possible beneficial effect of thymoquinone (TQ), the major active component of volatile oil of Nigella sativa seeds, against lead (Pb)-induced inhibition of rat testicular functions. Adult rats were randomized into four groups: a control group receiving no treatment; a Pb group exposed to 2000 parts per million (ppm) of Pb acetate in drinking water; a Pb-TQ group co-treated with Pb (as in Pb group) plus TQ (5 mg/kg body weight (b.w.)/day, per orally (p.o.)); and a TQ group receiving TQ (5 mg/kg b.w./day, p.o.). All treatments were for 5 weeks. No significant differences were observed for the body weight gain or for relative testes weight among the four groups of animals. Testicular Pb content significantly increased in metal-intoxicated rats compared with that in control rats. TQ supplementation had no effect on this testicular Pb accumulation. Interestingly, when coadministrated with Pb, TQ significantly improved the low plasma testosterone level and the decreased epididymal sperm count caused by Pb. In conclusion, the results suggest, for the first time, that TQ protects against Pb-induced impairment of testicular steroidogenic and spermatogenic functions. This study will open new perspectives for the clinical use of TQ in Pb intoxication.