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In our study, the protective role of synthetic aromatase inhibitors anastrozole (ANS), letrozole (LTZ) and exemestane (EXM) and natural aromatase inhibitors resveratrol (RSV) and apigenin (APG) against testicular failure caused by exposure to Bisphenol A (BPA) was investigated. The epididymal sperm concentration, sperm motility and sperm morphology were determined. Oxidative stress and inflammatory response parameters were examined and histological examinations were performed in testicular tissues. Our results revealed that BPA exposure decreased serum testosterone and estrogen levels, increased FSH and LH levels (p < 0.05). BPA has been found to increase oxidative stress and inflammatory response and disrupt the histological structure. Also, BPA exposure decreased testicular weight, epididymal sperm concentration and motility, and increased abnormal sperm rate (p < 0.05). These results show that ANS, LTZ and RSV treatments reduce the BPA-induced testicular damage. [ABSTRACT FROM AUTHOR]

Objective(s): This experiment was carried out to investigate the protective effects of curcumin (CUR) on testicular damage induced by the valproic acid (VPA) administration. Materials and Methods: Male Wistar-Albino rats (n=28, 250-300 g) were randomly divided into four groups: Control (1 ml saline, oral), VPA (500 mg/kg, IP), CUR (200 mg/kg, oral), or VPA+CUR (500 mg/kg, VPA, IP plus 200 mg/kg CUR, oral). The treatments were applied for 14 days. Serum testosterone and testis [Janus kinases1 (JAK1), signal transducers and activators of transcription-3 (STAT-3), interleukin-6 (IL-6), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-a), interleukin-18 (IL-18), and nuclear factor (NF)-κB)] samples were collected for biochemical analyses. Semen samples were subjected to microscopy for spermatological parameters. Testis tissue was also analyzed for histopathological and immunohistochemical methods. Results: The VPA administration caused a 37% decrease in serum testosterone concentration and 5.32, 9.51, 2.44, and 3.68-fold increases in testicular tissue JAK1, STAT-3, IL-6, and MDA levels, respectively. There were also 50, 52, and 72% reductions in sperm motility, sperm viability, and the mean testicular biopsy score, respectively, accompanied by considerable degenerative changes and necrosis in seminiferous tubules in the VPA group. There is also an immune-positive reaction for IL-18 and NF-κB in only Leydig cells. Conclusion: The CUR treatment may be beneficial in restoring testicular damage through antiinflammatory and anti-oxidant potential. [ABSTRACT FROM AUTHOR]

Cyclophosphamide (CP) is a popular cancer treatment; however, despite its efficacy, it is known to cause harm to the testicles. To mitigate the reproductive damage caused by CP in male rats, we examined the protective effect of azilsartan (AZ) on CP-induced testicular damage. Thirty Sprague–Dawley male rats were equally divided into three groups: normal control group: received 0.5% CMC suspension for 13 days; induction group: received a single dose of 200 mg/kg of CP on day 6 by intraperitoneal (IP) injection, azilsartan group: received azilsartan (4 mg/kg) orally for 5 days followed by a single dose of 200 mg/kg of (CP) on day 6 by IP injection, then azilsartan administered again for 7 days. Animals were sacrificed on day 14, and sperm characteristics, testosterone levels, and testicular histopathology were evaluated. Induction with CP caused a significant reduction in median value compared to normal control in sperm count (12.0 vs. 22.0 × 106/mm3), sperm motility (30 vs. 90%), abnormal sperm (30.32 vs. 14.43%), dead sperm count (32.43 vs. 10.49 × 106/mm3), DNA fragmentation (21.57 vs. 5.49%); meanwhile, azilsartan prevent these effects on median sperm count (17.0 × 106/mm3), sperm motility (70.0%), abnormal sperm (23.19%), dead sperm count (26.17 × 106/mm3), DNA fragmentation (13.81%), and improved plasmatic testosterone levels compared to the CP group and prevented histopathological alterations of the testes. Azilsartan's mitigation of CP's effects suggests it can prevent male rats' reproductive damage caused by CP. One possible explanation for AZ's protective effects is that it inhibits lipid peroxidation and has antioxidant properties. [ABSTRACT FROM AUTHOR]

Copyright of Kocatepe Veterinary Journal / Kocatepe Veteriner Dergisi is the property of Afyon Kocatepe University, Faculty of Veterinary Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The use of stem cells can attenuate testicular injury and promote sperm production. The adipose-derived stromal vascular fraction (SVF) has become an attractive cell source for cell-based therapies. In this study, we aimed to investigate the therapeutic efficacy of SVF on busulfan-induced testicular damage in rats. Twenty-four male rats were randomly divided into control, busulfan, SVF, and busulfan + SVF groups. Testicular damage was induced by intraperitoneal administration of busulfan (35 mg/kg). SVF obtained from human adipose tissue using Lipocube SVF™ was injected into rats 5 weeks after busulfan administration. At the end of the 8th week, rats were sacrificed, and histopathological, biochemical, and western blotting analyses were performed. No harmful effects of SVF on healthy testis tissue and sperm parameters were detected. SVF improved busulfan-induced oxidative stress in both testis tissue and serum. SVF injection to damaged testicular tissue resulted in increases in the healthy spermatozoon numbers and decreases in the abnormal tail numbers. Additionally, SVF increased bax/Bcl, DAZL, and TGF-β1 levels whereas decreased ATG5 and NF-kB levels. According to the results we obtained in this study, we suggest that SVF is beneficial in restoring damaged tissue by primarily being a multipotent cell source, by inhibiting oxidative stress and converting necrotic cell death to apoptotic cell death. In the future, clinical applications should bring higher benefits. Since SVF is the patient's own tissue, being harmless, it will offer an advantageous supportive treatment option for patients already weakened by cancer and anticancer therapy. [ABSTRACT FROM AUTHOR]

This study investigated the effects of transplanted testicular stromal stem cells (tSSCs) on surgically damaged testis tissue. Ten‐week‐old male Wistar albino rats were divided into three groups: control (n = 6), damage (DG) (n = 6) and testicular stromal stem cell (TSSC) (n = 6) groups. Surgically induced damage was inflicted on the left testes of both the DG and TSSC groups, with no intervention on the right testes. In the TSSC group, damaged testes were treated with transplanted tSSCs, followed by orchiectomy after 15 days. Testes tissues were stained with haematoxylin–eosin (H&E), and recovery rates of functional structures were assessed by modified Johnsen scoring. The effects of tSSCs on testicular tissue were demonstrated by immunohistochemistry using BAX, BCL‐2 and caspase 3. Serum testosterone levels were analysed using the enzyme‐linked immunosorbent assay (ELISA) method. Surgical damage caused germ cell degeneration in some seminiferous tubules and a decrease in interstitial areas. With tSSC treatment, improvements in testicular architecture were identified through spermatogenesis in the seminiferous tubules and normal histological structures in the interstitial areas. Correspondingly, in the modified Johnsen score, the DG group showed a significant difference compared to the other groups (p = 0.001). High expressions of BAX, BCL‐2 and caspase‐3 in the DG group revealed prominent features of apoptosis. With the injection of tSSCs, these expressions significantly normalized according to H score analysis (all p = 0.004). Although serum testosterone levels in the tSSC group were higher compared to the control and DG groups, this difference was not statistically significant (p = 0.119). This study suggests transplanting tSSCs could accelerate tissue healing after testicular sperm extraction (TESE) surgery for azoospermia patients, potentially paving the way for a new and important clinical treatment. [ABSTRACT FROM AUTHOR]

Fluoride and aluminum are ubiquitous toxic metals with adverse reproductive effects. The citrus flavonoid hesperidin has protective activities but poor solubility and bioavailability. Nanoparticulate delivery systems can improve flavonoid effectiveness. We conducted this study to prepare a pH-responsive chitosan-based nanogel for hesperidin delivery and evaluate its effectiveness against sodium fluoride (NaF) and aluminum chloride (AlCl3) induced testicular toxicity in mice. The nanogel was synthesized using 2 kGy gamma irradiation, enabling a size under 200 nm and enhanced hesperidin release at pH 6 matching testicular acidity. Male mice received 200 mg/kg AlCl3 and 10 mg/kg NaF daily for 30 days. Hesperidin nanogel at 20 mg/kg was administered orally either prophylactically (pretreatment) or after intoxication (posttreatment). The results showed that AlCl3 + NaF induced severe oxidative stress, hormonal disturbance, apoptosis, and endoplasmic reticulum stress, evidenced by significant changes in the studied parameters and testicular histological damage. Hesperidin nanogel administration significantly inhibited oxidative stress markers, restored luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels, and alleviated tissue damage compared to the intoxicated group. It also downregulated the expression level of pro-apoptotic genes Bax, caspase-3, caspase-9, and P38MAPK, while upregulating the expression level of the anti-apoptotic BCL2 gene. Endoplasmic reticulum stress sensors PERK, ATF6, and IRE-α were also downregulated by the nanogel. The chitosan-based nanogel enhanced the delivery and efficacy of poorly bioavailable hesperidin, exhibiting remarkable protective effects against AlCl3 and NaF reproductive toxicity. This innovative nanosystem represents a promising approach to harnessing bioactive phytochemicals with delivery challenges, enabling protective effects against chemical-induced testicular damage. [ABSTRACT FROM AUTHOR]

One of the adverse effects of the antineoplastic drug cisplatin (CS) is damage to testicular tissue. This study aimed to examine the potential therapeutic effect of thymoquinone (TQ), a strong antioxidant, against testicular damage caused by CS. In the experiment, 28 rats were used, and the rats were randomly divided into four groups: control (n = 7), CS (n = 7), CS + TQ (n = 7), and TQ (n = 7). The experiment was called off after all treatments were finished on day 15. Blood serum and testicular tissues were utilized for biochemical, histological, immunohistochemical, mRNA expression, and gene protein investigations. The testosterone level decreased and oxidative stress, histopathological damage, dysregulation in mitochondrial dynamics, inflammation and apoptotic cells increased in testicular tissue due to CS administration. TQ supplementation showed anti-inflammatory, antioxidant, and anti-apoptotic effects in response to CS-induced testicular damage. In addition, TQ contributed to the reduction of CS-induced toxic effects by regulating the TNF-α/OTULIN/NF-κB pathway. TQ supplementation may be a potential therapeutic strategy against CS-induced testicular damage by regulating the TNF-α/OTULIN/NF-κB axis, inhibiting inflammation, oxidative stress, and apoptosis. [ABSTRACT FROM AUTHOR]

Researchers have demonstrated the therapeutic properties of natural products like Crassocephalum rubens against a range of clinical conditions that involve oxidative stress. In this study the effect of an aqueous extract of Crassocephalum rubens (AECR) leaves on the potential of testicular damage from cisplatin was investigated. Thirty adult male Wistar rats (150-240 g) were randomly assigned into 5 groups (n = 6) and used for the study. Group A was administered 2 ml/kg of distilled water as the normal control; groups B and C were administered 300 mg/kg and 450 mg/kg AECR, respectively, for 14 days; and cisplatin (5 mg/kg) was administered on days 7 and 14 to both groups. Groups D and E received 450 mg/kg AECR and 5 mg/kg of cisplatin, respectively, on days 7 and 14. Cisplatin and extract administration was done intraperitoneally and orally, respectively. Testicular tissue histology was assessed using Hematoxylin and eosin procedures. Statistical data were analysed using ANOVA and the tukey test. There was no statistically significant difference (p = 0.3405; F = 1.193) in the body weight change when all groups were compared to the control. Testicular weight showed a statistically significant difference in weight reduction (p< 0.0001; F = 16.85) in groups D and E Histological evaluation showed severe histoarchietctural derangement in testicular morphology, with no clearly distinguishable tubular lumen, in the cisplatin only group, while these were ameliorated in the extract treated groups. In conclusion, AECR at 300 and 450 mg/kg possesses protective effect against cisplatin-induced testicular toxicity. [ABSTRACT FROM AUTHOR]

Chemotherapeutic drugs have demonstrated effectiveness in treating various neoplastic conditions; however, they can also have detrimental effects on male gonadal function and fertility. Consequently, interest has grown in identifying novel approaches that can mitigate chemotherapy-induced testicular damage. Thymoquinone (TQ), the chief active component of the volatile oil of Nigella sativa (NS), has a wide range of therapeutic properties, including antioxidant, anti-inflammatory and anti-apoptotic effects. The aim of this systematic review was to identify experimental animal studies that have evaluated the protective effects of TQ against testicular complications associated with chemotherapy. In accordance with the preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines, a thorough search was performed across several databases (PubMed, EBSCOhost, Sage and Scopus) to identify experimental studies published from 2010 to May 2022 that focused on rodent models and compared the effects of TQ versus other chemotherapeutic drugs. Eight studies met the inclusion criteria, comparing TQ with methotrexate (MTX), 6-mercaptopurine (6-MP), cyclophosphamide (CPA), bleomycin (BL), doxorubicin (DOX) or busulfan (BUS). The results of these studies consistently demonstrated that TQ significantly improved sperm parameters, the levels of oxidative stress (OS) markers, apoptosis markers, and hormones and testicular histopathology, indicating that TQ has protective effects against chemotherapy-induced damage. TQ mitigated chemotherapy-induced testicular toxicity by decreasing lipid peroxidation and enhancing the activity of antioxidant enzymes within chemotherapy-treated testes. These findings highlight the potential of TQ as a therapeutic agent that can ameliorate testicular complications associated with chemotherapy, thereby providing a basis for further research and potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Busulfan, an indispensable medicine in cancer treatment, can cause serious reproductive system damage to males as a side effect of its otherwise excellent therapeutic results. Its widespread use has also caused its accumulation in the environment and subsequent ecotoxicology effects. As a Chinese medicine, Wulingzhi (WLZ) has the effects of promoting blood circulation and improving female reproductive function. However, the potential effects of WLZ in male reproduction and in counteracting busulfan-induced testis damage, as well as its probable mechanisms, are still ambiguous. In this study, busulfan was introduced in a mouse model to evaluate its production of the testicular damage. The components of different WLZ extracts were compared using an untargeted metabolome to select extracts with greater efficacy, which were further confirmed in vivo. Here, we demonstrate abnormal spermatogenesis and low sperm quality in busulfan-injured testes. The WLZ extracts showed a strong potential to rehabilitate the male reproductive system; this effect was more prominent in room-temperature extracts. Additionally, both water and ethanol WLZ extracts at room temperature alleviated various busulfan-induced adverse effects. In particular, WLZ recovered spermatogenesis, re-activated arginine biosynthesis, and alleviated the increased oxidative stress and inflammation in the testis, ultimately reversing the busulfan-induced testicular injury. Collectively, these results suggest a promising approach to protecting the male reproductive system from busulfan-induced adverse side effects, as well as those of other similar anti-cancer drugs. [ABSTRACT FROM AUTHOR]

The current research was planned to evaluate the ameliorative role of juglanin (Jug) against polyethylene microplastics (PEMP) prompted testicular impairments. 48 rats were allocated in 4 groups: control, PEMP exposed, Jug + PEMP co-administrated and Jug supplemented group. The activities of antioxidant enzyme, inflammatory markers level, hormonal level, the expressions of steroidogenic enzymes, pro-apoptotic and anti-apoptotic protein were assessed after the 56 days of the trial. PEMP intoxication significantly disturbed Nrf-2/Keap-1 pathway and the biochemical profile of rats. However, the administration of Jug markedly increased Nrf-2 and anti-oxidant enzymes expressions, besides decreased the Keap-1 expression. Jug administration also increased Catalase (CAT), super oxide dismutase (SOD) glutathione reductase (GPx), glutathione peroxidase (GSR) and Hemeoxygenase-1 (HO-1) activities. On the other hand, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were decreased following Jug administration. Moreover, Jug administration decreased the levels of inflammatory markers. Additionally, Jug administration increased luteinizing hormone (LH), testosterone, follicle-stimulating hormone (FSH) levels and steroidogenic enzymes expression including 17β-hydroxysteroid dehydrogenase (17β-HSD), steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) expressions. Jug administration decreased Caspase-3 and Bax expressions, while increasing Bcl-2 expression. Therefore, the current findings suggested that Jug can remarkably alleviate PEMP induced testicular damage due to its therapeutical potentials.

Abstract Doxorubicin (DOX) is a highly effective, commonly prescribed, potent anti-neoplastic drug that damages the testicular tissues and leads to infertility. Apigetrin (APG) is an important flavonoid that shows diverse biological activities. The present research was designed to evaluate the alleviative role of APG against DOX-induced testicular damages in rats. Forty-eight adult male albino rats were randomly distributed into 4 groups, control, DOX administered (3 mgkg−1), DOX + APG co-administered (3 mgkg−1 of DOX; 15 mgkg−1 of APG), and APG administered group (15 mgkg−1). Results of the current study indicated that DOX treatment significantly reduced the activities of superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT) and glutathione peroxidase (GPx), while increasing the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). DOX treatment also reduced the sperm count, viability, and motility. Moreover, DOX significantly increased the sperm morphological anomalies and reduced the levels of plasma testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The administration of DOX significantly increased the expressions of Bax and Caspase-3, as well as the levels of inflammatory markers. Additionally, DOX treatment significantly downregulated the expressions of steroidogenic enzymes (StAR, 3β-HSD and 17β-HSD) and Bcl-2. Furthermore, DOX administration provoked significant histopathological abnormalities in the testicular tissues. However, APG supplementation significantly reversed all the testicular damages due to its androgenic, anti-apoptotic, anti-oxidant and anti-inflammatory nature. Therefore, it is concluded that APG may prove a promising therapeutic agent to treat DOX-induced testicular damages.

Introduction: Fabry's disease (FD) is a genetic X-linked systemic and progressive rare disease characterized by the accumulation of globotriaosylceramide (GB3) into the lysosomes of many tissues. FD is due to loss-of-function mutations of α-galactosidase, a key-enzyme for lysosomal catabolism of glycosphingolipids, which accumulate as glycolipid bodies (GB). In homozygous males the progressive deposition of GB3 into the cells leads to clinical symptoms in CNS, skin, kidney, etc. In testis GB accumulation causes infertility and alterations of spermatogenesis. However, the precise damaging mechanism is still unknown. Our hypothesis is that GB accumulation reduces blood vessel lumen and increases the distance of vessels from both stromal cells and seminiferous parenchyma; this, in turn, impairs oxygen and nutrients diffusion leading to subcellular degradation of seminiferous epithelium and sterility. Methods: To test this hypothesis, we have studied a 42-year-old patient presenting a severe FD and infertility, with reduced number of spermatozoa, but preserved sexual activity. Testicular biopsies were analyzed by optical (OM) and transmission electron microscopy (TEM). Activation and cellular localization of HIF-1α and NFκB was analyzed by immunofluorescence (IF) and RT-PCR on homogeneous tissue fractions after laser capture microdissection (LCMD). Results: OM and TEM showed that GB were abundant in vessel wall cells and in interstitial cells. By contrast, GB were absent in seminiferous epithelium, Sertoli's and Leydig's cells. However, seminiferous tubular epithelium and Sertoli's cells showed reduced diameter, thickening of basement membrane and tunica propria, and swollen or degenerated spermatogonia. IF showed an accumulation of HIF-1α in stromal cells but not in seminiferous tubules. On the contrary, NFκB fluorescence was evident in tubules, but very low in interstitial cells. Finally, RT-PCR analysis on LCMD fractions showed the expression of proinflammatory genes connected to the HIF-1α/NFκB inflammatory-like pathway. Conclusion: Our study demonstrates that infertility in FD may be caused by reduced oxygen and nutrients due to GB accumulation in blood vessels cells. Reduced oxygen and nutrients alter HIF-1α/NFκB expression and localization while activating HIF-1α/NFκB driven-inflammation-like response damaging seminiferous tubular epithelium and Sertoli's cells. [ABSTRACT FROM AUTHOR]

Purpose: 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent environmental toxicants, which causes oxidative stress and adversely affects the male reproductive system. The current study aimed to evaluate the ameliorative role of didymin (DDM) against TCDD-induced testicular toxicity. Methods: Forty-eight male Sprague–Dawley rats were divided into four equal groups (n=12). (i) Control group, (ii) TCDD-induced group was provided with 10 μg/kg/day of TCDD, (iii) TCDD + DDM group received 10 μg/kg/day of TCDD and 2 mg/kg/day of DDM, and (iv) DDM-treated group was administered with 2 mg/kg/day of DDM. After 56 days of treatment, biochemical, steroidogenic, hormonal, spermatogenic, apoptotic, and histopathological parameters were estimated. Results: TCDD affected the biochemical profile by reducing the activities of antioxidant enzymes, while increasing the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). Furthermore, it decreased the expressions of steroidogenic enzymes, 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1), and 17α-hydroxylase/17, 20-lyase (CYP17A1), as well as reduced the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and plasma testosterone. Besides, epididymal sperm count, viability, and motility were decreased, while sperm morphological anomalies were increased. Moreover, TCDD altered the apoptotic profile by up-regulating the expressions of Bax and caspase-3, while downregulated the Bcl-2 expression. Additionally, histopathological damages were prompted due to TCDD administration. However, DDM restored all the TCDD-induced damages owing to its antioxidant, anti-apoptotic, and androgenic potential. Conclusion: Our data suggested that DDM might play its role as a therapeutic agent against TCDD-prompted testicular toxicity. [ABSTRACT FROM AUTHOR]

Asteriscus graveolens (Asteraceae) is a medicinal herb, used in Algeria to treat diabetes, hypertension, pain, fever, inflammation and gastrointestinal diseases. Doxorubicin (DOX) is an antibiotic antineoplastic drug used to treat many types of cancers; unfortunately, its antitumor activity links toxic effects to several organs including the heart, liver and testis. The appropriate mechanism of its organotoxicity is linked to free reactive oxygen species (ROS) generation and oxidative stress induction. In this study, the antioxidant and protective role of A. graveolens and vitamin E (Vit E) against DOX-induced hepatic and testicular toxicity was assessed. Thirty-five rats were distributed equally into five groups and orally administered with n-butanol extract of A. graveolens (75 mg/kg bw) or Vit E (100 mg/kg bw) for 10 days in the absence or presence of a single intraperitoneal injection of DOX (15 mg/kg bw). The results revealed that DOX toxicity induced a significant elevation in the liver serum marker enzymes and lipid profile levels (cholesterol, triglycerides and LDL). In addition, DOX-induced hepatic and testicular oxidative injury was indicated due to a significant increase of malondialdehyde levels along with a noticeable reduction of the antioxidant system. A. graveolens and Vit E treatment might improve the biochemical and histopathological changes induced by DOX. A. graveolens has antioxidant and hypolipidemic properties and it can reduce DOX-induced oxidative damage in the liver and testis. A. graveolens showed a similar protective effect of Vit E against DOX damage due to the presence of an abundant amount of phenolics such as flavonoids. This protection is mediated by their direct free-radical scavenging activity and their ability to prevent DOX depletion of the hepato-testicular antioxidant defense systems. [ABSTRACT FROM AUTHOR]

Di‐(2‐ethylhexyl) phthalate (DEHP), a widely used plasticizer, has been shown to cause reproductive toxicity, but the precise mechanism remains unclear. This study aimed to investigate the possible molecular mechanism of DEHP‐induced testicular damage. In vivo study, we administered different doses of DEHP (0, 250, and 500 mg/kg/day) to male C57BL/6 mice from 22 and 35 days after birth. We found that DEHP exposure induced histopathological alterations in prepubertal testes, and testicular lipidomics indicated notable alterations in lipid metabolism and significant enrichment of ferroptosis. Further tests showed that ferrous iron (Fe2+) and malondialdehyde (MDA) levels significantly increased after DEHP exposure. Western blotting revealed that DEHP exposure reduced glutathione peroxidase 4 (GPX4) expression, and elevated acyl coenzyme A synthetase long‐chain member 4 (ACSL4) and lysophosphatidylcholine acyltransferase 3 (LPCAT3) expression. The in vitro results were consistent with the in vivo results. When Leydig cells and Sertoli cells were treated with ferrostatin‐1 and monoethylhexyl phthalate (MEHP), MEHP‐induced increases in Fe2+ and MDA levels, accumulation of lipid reactive oxygen species, downregulation of GPX4, and upregulation of ACSL4 and LPCAT3 were reversed. Collectively, our findings suggested that aberrant lipid metabolism and ferroptosis may be involved in prepubertal DEHP exposure‐induced testicular damage. [ABSTRACT FROM AUTHOR]

Diabetic testicular damage is quite a common and significant complication in diabetic men, which could result in infertility. The natural fertility rate of type 1 diabetes men is only 50% because of testicular damage. This research first aimed to explore the intervention effect of C3G on testicular tissue damage induced by diabetes. Here, a streptozotocin-induced type 1 diabetic rat model was established, and then C3G was administered. After 8 weeks of C3G supplementation, the symptoms of diabetes (e.g., high blood glucose, lower body weight, polydipsia, polyphagia) were relieved, and at the same time that sperm motility and viability increased, sperm abnormality decreased in C3G-treated diabetic rats. Furthermore, the pathological structure of testis was restored; the fibrosis of the testicular interstitial tissue was inhibited; and the LH, FSH, and testosterone levels were all increased in the C3G-treated groups. Testicular oxidative stress was relieved; serum and testicular inflammatory cytokines levels were significantly decreased in C3G-treated groups; levels of Bax, Caspase-3, TGF-β1 and Smad2/3 protein in testis decreased; and the level of Bcl-2 was up-regulated in the C3G-treated groups. A possible mechanism might be that C3G improved antioxidant capacity, relieved oxidative stress, increased anti-inflammatory cytokine expression, and inhibited the apoptosis of spermatogenic cells and testicular fibrosis, thus promoting the production of testosterone and repair of testicular function. In conclusion, this study is the first to reveal that testicular damage could be mitigated by C3G in type 1 diabetic rats. Our results provide a theoretical basis for the application of C3G in male reproductive injury caused by diabetes. [ABSTRACT FROM AUTHOR]

Copyright of Cirugía y Cirujanos is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Diquat dibromide (DQ) is a globally used herbicide in agriculture, and its overuse poses an important public health issue, including male reproductive toxicity in mammals. However, the effects and molecular mechanisms of DQ on testes are limited. In vivo experiments, mice were intraperitoneally injected with 8 or 10 mg/kg/ day of DQ for 28 days. It has been found that heme oxygenase-1 (HO-1) mediates DQ-induced ferroptosis in mouse spermatogonia, thereby damaging testicular development and spermatogenesis. Histopathologically, we found that DQ exposure caused seminiferous tubule disorders, reduced germ cells, and increased sperm malformation, in mice. Reactive oxygen species (ROS) staining of frozen section and transmission electron microscopy (TEM) displayed DQ promoted ROS generation and mitochondrial morphology alterations in mouse testes, suggesting that DQ treatment induced testicular oxidative stress. Subsequent RNA-sequencing further showed that DQ treatment might trigger ferroptosis pathway, attributed to disturbed glutathione metabolism and iron homeostasis in spermatogonia cells in vitro. Consistently, results of western blotting, measurements of MDA and ferrous iron, and ROS staining confirmed that DQ increased oxidative stress and lipid peroxidation, and accelerated ferrous iron accumulation both in vitro and in vivo. Moreover, inhibition of ferroptosis by deferoxamine (DFO) markedly ameliorated DQ-induced cell death and dysfunction. By RNA-sequencing, we found that the expression of HO-1 was significantly upregulated in DQ-treated spermatogonia, while ZnPP (a specific inhibitor of HO-1) blocked spermatogonia ferroptosis by balancing intracellular iron homeostasis. In mice, administration of the ferroptosis inhibitor ferrostatin-1 effectively restored the increase of HO-1 levels in the spermatogonia, prevented spermatogonia death, and alleviated the spermatogenesis disorders induced by DQ. Overall, these findings suggest that HO-1 mediates DQ-induced spermatogonia ferroptosis in mouse testes, and targeting HO-1 may be an effective protective strategy against male reproductive disorders induced by pesticides in agriculture.

Cadmium (Cd) is a toxic heavy metal that is known to accumulate in various organs and tissues in the body, including the testes. Exposure to Cd has been shown to cause significant testicular damage, including impaired spermatogenesis and decreased fertility in both humans and animals. This damage is thought to be due to Cd-induced oxidative stress and inflammation, which can lead to cellular damage and apoptosis. Cd has also been shown to disrupt the blood-testis barrier, leading to increased permeability and an altered testicular microenvironment. In addition, Cd exposure has been linked to changes in hormone levels, including decreased testosterone production and altered gonadotropin secretion. Reactive oxygen species (ROS) and an imbalance in the activity of antioxidant enzymes cause oxidative stress. The nuclear factor kappa-B (NF-κB) signaling system, which controls multiple genes involved in inflammatory responses including tumor necrosis factor (TNF-α), is activated by oxidative stress. These effects can contribute to decreased sperm count, motility, and viability. Efforts to reduce exposure to Cd may help to prevent or mitigate the harmful effects on testicular function. This can be achieved through occupational and environmental regulations, as well as public education and awareness programs. In this review, we highlight many of the principal mechanisms included in testicular damage. These pathways could be considered promising targets for the development of potential therapies for a variety of important human diseases.

Background: Sodium nitrite (NaNO2) is a chemical substance used to enhance taste, add color, and keep food products fit for consumption for a longer time. NaNO2 gives rise to a negative adverse effect on male reproductive function. Odontonema cuspidatum (OC) is a natural plant that possesses antioxidant capacity. Aim: Our research evaluates the potential beneficial effect of Odontonema cuspidatum extract on the harmful effects caused by NaNO2 on the testicular tissue and sperm characteristics of male rats. Methods: Four groups with a total of forty rats: the control, the NaNO2-received group, the OC-administered group, and the fourth group received both NaNO2 and OC. All groups were administered daily for two months. Sperm characteristics, testicular antioxidant status and histopathological changes were evaluated. Results: Coadministration of NaNO2 and OC, in comparison with NaNO2 alone, contributed to a notable enhancement in acrosomal integrity, decreasing sperm abnormalities and restoring serum testosterone levels. Moreover, such coadministration reduced the oxidative stress marker, MDA, and increased SOD in testicular tissue, lowering TNF-α gene expression, and increasing the expression of P450scc and StAR genes. Additionally, the NaNO2 and OC combination decreased the testicular histopathological changes and the Caspase-3 and PCNA immunoexpression in seminiferous tubules compared with the NaNO2 group. Conclusion: The extract of Odontonema cuspidatum exhibited the ability to decrease oxidative stress and ameliorate the detrimental effects caused by NaNO2. [Open Vet J 2024; 14(1.000): 304-315]

Introduction: Diabetes causes damage to various tissues, including the testicles. Garlic and Cambodian mushrooms play an important role in preventing diabetes complications in the testicles due to their antioxidant properties. The present study aimed to investigate the effect of Cambodian mushroom extract and garlic on testicular damage in healthy and diabetic desert mice. Methods: 40 male Wistar rat heads were divided into 5 groups of 8, including control group, negative control group (witness) (diabetic, with mg/kg 55 Streptozotocin intraperitoneal), experimental group 1 (diabetic + mg/kg 50 garlic extract), experimental group 2 (diabetic + 50 mg/kg Cambodian mushroom), and experimental group 3 (diabetic + mg/kg 50 Cambodian mushroom and mg/kg 50 garlic extract). After two months of diabetes, the mice received the extracts subcutaneously for two weeks. The mice were then anesthetized with ketamine and xylazine, and the testes were examined macroscopically and microscopically. Results: The diabetic group showed a significant decrease in spermatogenic cells compared to the control group. Conversely, the experimental groups showed a significant increase in spermatogenic cells compared to the diabetic group. Conclusion: The findings of this study demonstrate that prolonged oral intake of garlic and Cambodian extract enhances the secretion of the blood hormones insulin and testosterone, and promotes the spermatogenesis process. [ABSTRACT FROM AUTHOR]

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Background: Sodium nitrite (NaNO2) is a chemical substance used to enhance taste, add color, and keep food products fit for consumption for a longer time. NaNO2 gives rise to a negative adverse effect on male reproductive function. Odontonema cuspidatum (OC) is a natural plant that possesses antioxidant capacity. Aim: Our research evaluates the potential beneficial effect of OC extract on the harmful effects caused by NaNO2 on the testicular tissue and sperm characteristics of male rats. Methods: Four groups with a total of forty rats: the control, the NaNO2 -received group, the OC-administered group, and the fourth group received both NaNO2 and OC. All groups were administered daily for two months. Sperm characteristics, testicular antioxidant status, qRT-PCR, and histopathological changes were evaluated. Results: Coadministration of NaNO2 and OC, in comparison with NaNO2 alone, contributed to a notable enhancement in acrosomal integrity, decreasing sperm abnormalities and restoring serum testosterone levels. Moreover, such coadministration reduced the oxidative stress marker, malondialdehyde (MDA), and increased superoxide dismutase (SOD) in testicular tissue, lowering TNF-α gene expression, and increasing the expression of P450scc and StAR genes. In addition, the NaNO2 and OC combination decreased the testicular histopathological changes and the Caspase-3 and Proliferating cell nuclear antigen (PCNA) immunoexpression in seminiferous tubules compared with the NaNO2 group. Conclusion: The extract of OC exhibited the ability to decrease oxidative stress and ameliorate the detrimental effects caused by NaNO2. [ABSTRACT FROM AUTHOR]

Gamma radiation, an ionising radiation, impairs the reproductive potential. Chloroquine is a class of antimalarial drugs currently used for the treatment of various diseases including cancer and viral infections and is a late autophagy inhibitor. It is known that apocynin has a vital role in reducing oxidative stress. We aim to evaluate the damage caused by radiation and chloroquine on testicular tissue and determine the effects of apocynin administration on male reproductive capacity as a protective factor to reduce or prevent damage histopathologically and biochemically. Male rats (n = 56) were divided into 8 groups. Control, chloroquine, apocynin, radiation, chloroquine + apocynin, chloroquine + radiation, apocynin + radiation, chloroquine + apocynin + radiation. The rats were sacrificed, testicular tissues and blood samples were collected for histological and biochemical examinations. In the radiation and chloroquine groups, enlargement of the intercellular spaces, and morphological damage parameters were observed in the testis tissues. Histological findings were reversed in the apocynin treated groups. Biochemical parameters revealed that damage occurred in the groups given chloroquine and radiation. The damages were reversed or attenuated by the administration of apocynin to the groups. It was concluded that apocynin plays a protective/therapeutic role by reducing histological and biochemical damage, as well as regulates oxidant/antioxidant balance in testicular tissue. [ABSTRACT FROM AUTHOR]

Crocin, a pharmacologically active component of Crocus sativus L. (saffron), has been informed to be beneficial in the treatment of stress‐related oxidative impairment. In the present study, we examined the protective role of crocin against testicular damage induced by radiation (acute and fractionated) and the alteration of the AKT/FOXO signaling pathway. Male Wister albino rats were exposed to acute dose of 6 Gy and a fractionated dose of gamma radiation (2 Gy every 2 days up to 6 Gy total doses). Rats were pretreated intraperitoneally with crocin in a dose of 50 mg/kg for seven consecutive days prior to exposure to irradiation at a level of 6 Gy and during the fractionated irradiation of rats. Control groups were run concurrently. Ionizing radiation caused changes in the level of oxidative stress biomarkers manifested as elevation of thiobarbituric acid reactive substance, total nitrate/nitrite and reactive oxygen species (ROS) associated with a decrease in catalase as well as in the level of inflammatory parameters (decrease in expression of Nrf2 which was related to a significant increase in expression of NF‐κB p65). Irradiation produced cellular damage characterized by an increase in serum lactate dehydrogenase. These findings were aligned with increased expression of the forkhead box O‐1 (FOXO‐1) and activation of protein kinase B (AKT) pathway. Irradiation of rats led to reduction in serum testosterone level and testicular weights. Pretreatment with the indicated dose of crocin shielded against the changes in all the evaluated parameters. Administration of crocin can be introduced as a novel preclinical approach for regulation of testicular damage induced by radiation; via controlling the ongoing oxidative stress and inflammatory reaction as well as activation FOXO/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

IntroductionFabry’s disease (FD) is a genetic X-linked systemic and progressive rare disease characterized by the accumulation of globotriaosylceramide (GB3) into the lysosomes of many tissues. FD is due to loss-of-function mutations of α-galactosidase, a key-enzyme for lysosomal catabolism of glycosphingolipids, which accumulate as glycolipid bodies (GB). In homozygous males the progressive deposition of GB3 into the cells leads to clinical symptoms in CNS, skin, kidney, etc. In testis GB accumulation causes infertility and alterations of spermatogenesis. However, the precise damaging mechanism is still unknown. Our hypothesis is that GB accumulation reduces blood vessel lumen and increases the distance of vessels from both stromal cells and seminiferous parenchyma; this, in turn, impairs oxygen and nutrients diffusion leading to subcellular degradation of seminiferous epithelium and sterility.MethodsTo test this hypothesis, we have studied a 42-year-old patient presenting a severe FD and infertility, with reduced number of spermatozoa, but preserved sexual activity. Testicular biopsies were analyzed by optical (OM) and transmission electron microscopy (TEM). Activation and cellular localization of HIF-1α and NFκB was analyzed by immunofluorescence (IF) and RT-PCR on homogeneous tissue fractions after laser capture microdissection (LCMD).ResultsOM and TEM showed that GB were abundant in vessel wall cells and in interstitial cells. By contrast, GB were absent in seminiferous epithelium, Sertoli’s and Leydig’s cells. However, seminiferous tubular epithelium and Sertoli’s cells showed reduced diameter, thickening of basement membrane and tunica propria, and swollen or degenerated spermatogonia. IF showed an accumulation of HIF-1α in stromal cells but not in seminiferous tubules. On the contrary, NFκB fluorescence was evident in tubules, but very low in interstitial cells. Finally, RT-PCR analysis on LCMD fractions showed the expression of pro-inflammatory genes connected to the HIF-1α/NFκB inflammatory-like pathway.ConclusionOur study demonstrates that infertility in FD may be caused by reduced oxygen and nutrients due to GB accumulation in blood vessels cells. Reduced oxygen and nutrients alter HIF-1α/NFκB expression and localization while activating HIF-1α/NFκB driven-inflammation-like response damaging seminiferous tubular epithelium and Sertoli’s cells.

The research investigates the effects of freeze-dried Spirulina maxima microcapsules in reducing testicular toxicity in rats and optimizing the in vitro release behavior of milk beverages using response surface methodology (RSM). Particle size, polydispersity index and zeta-potential were impacting microcapsules’ stability and bioactivity. Thirty-six male Sprague-Dawley rats were utilized; eighteen of them received cadmium orally at a dose of 0.5 mg/mL/rat/d. The nutritional and biochemical parameters were evaluated. Non-encapsulated and Spirulina maxima microcapsules exhibited no significant adverse consequences in vitro experiment. Spirulina maxima microcapsules defended rats against both the inflammatory and apoptotic consequences triggered by cadmium. Incorporating Spirulina maxima microcapsules into the milk beverage at 3 % optimized in vitro release behavior of antioxidants and phenolics due to the increasing importance of these compounds' biological activity. Spirulina maxima microcapsules guide as a viable approach for providing nutritional enrichment in the food industry; moreover, protecting against cadmium-induced oxidative testicular damage in rats.

Chromium picolinate (CP) is an organic compound that has long been used to treat diabetes. Our previous studies found CP could relieve diabetic nephropathy. Thus, we speculate that it might have a positive effect on diabetic testicular injury. In this study, a diabetic rat model was established, and then the rats were treated with CP for 8 weeks. We found that the levels of blood glucose, food, and water intake were reduced, and body weight was enhanced in diabetic rats after CP supplementation. Meanwhile, in CP treatment groups, the levels of male hormone and sperm parameters were improved, the pathological structure of the testicular tissue was repaired, and testicular fibrosis was inhibited. In addition, CP reduced the levels of serum inflammatory cytokines, and decreased oxidative stress and apoptosis in the testicular tissue. In conclusion, CP could ameliorate testicular damage in diabetic rats, as well as being a potential testicle-protective nutrient in the future to prevent the testicular damage caused by diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Diabetes mellitus (DM) has been considered a major problem because of its related complications and growing incidence worldwide. Testicular dysfunction has become a predominant diabetic complication characterized by impaired reproductive function and testicular damage. Stevia rebaudiana Bertoni has been known for its antioxidant effect on diabetes, inflammation, and obesity. The current study investigates the protective effect of Stevia on diabetic-induced testicular injury. MATERIALS AND METHODS: Sprague Dawley adult male rats were divided into three groups: the control group, the diabetic group, and the diabetic + Stevia group, type 2 diabetes is induced by a high-fat diet (HFD) and a single dose of 35 mg/kg streptozotocin injection. The effects of Stevia were evaluated regarding biochemical, oxidative stress, histopathological and ultrastructural changes, and immunohistochemical expression of vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), receptor-interacting serine/threonine-protein kinase 1 (RIPK 1), and caspase 3. RESULTS: Stevia extract attenuated the diabetic-induced oxidative stress, restored the testicular architecture, and decreased testicular damage, inflammation, necroptosis, and apoptosis by upregulating VEGF and downregulating VCAM 1, RIPK 1, and caspase 3. CONCLUSIONS: The current study highlights the importance of Stevia as an antioxidant anti-inflammatory that ameliorates diabetic-induced testicular injury by modulating oxidative stress, inflammation, necroptosis, and apoptosis. [ABSTRACT FROM AUTHOR]

The aim of this study is to reveal the gonadoprotective effects of myricetin (MYC), which has many biological properties, on cisplatin (CP)-induced testicular damage in rats. For this purpose, 40 male Wistar albino rats were divided into 4 groups as Control (group given no treatment), MYC (group given 5 mg/kg/i.p myricetin for 7 days), CP (group given 7 mg/kg/i.p cisplatin at 7th day) and MYC + CP (group given 5 mg/kg/i.p myricetin for 7 days before 7 mg/kg/i.p cisplatin injection). After administrations, testicular tissues of animals were extracted and processed according to tissue processing protocol. Hematoxylin & Eosin staining were performed to evaluate the histopathological changes and Johnsen'sTesticular Biopsy Score (JTBS) was applied and mean seminiferous tubule diameters (MSTD) were measured to compare experimental groups in terms of histopathological changes. Moreover, TLR4, NF-kB, HSP70 and HSP90 expression levels were detected by immunohistochemical staining and the density of immunoreactivity were measured to determine the difference in the expression levels of these factors among groups. Additionally, testicular apoptosis was detected via TUNEL assay. JTBS and MSTD data were significantly lower in CP group compared to other groups and MYC administrations significantly protects testicular tissue against CP-induced damage. Moreover, TLR4, NF-kB, HSP70 and HSP90 expressions and apoptotic cells significantly increased in the CP group (p<0.05). However, MYC administrations exerted a strong gonadoprotective effect on testicular tissue in terms of these parameters in MYC+CP group (p<0.05). According to our results, we suggested that MYC can be considered as a protective agent against cisplatin-induced testicular damage. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The present research aimed to study the possible protective effects of Silymarin on testicular I/R injury in a rat model evaluated through histopathology and biochemical parameters. MATERIALS AND METHODS: This research investigated the impact of Silymarin on IR damage in male Wistar albino rats. Animals were divided into three groups: group 1 (sham), group 2 (IR), and group 3 (IR+Silymarin). RESULTS: There were no notable differences in the levels of malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH) across the three groups (p=0.260, p=0.486 and p=0.803, respectively). Contrarily, the total antioxidant status (TAS) levels exhibited significant variations between groups (p=0.001). The total oxidant status (TOS) levels also differed significantly between groups (p=0.004). The tissue evaluations uncovered substantial differences in the Johnson score, which is used to gauge testicular damage. A distinct contrast was seen between Group 1 and Group 2, and also between Group 2 and Group 3, with an all-encompassing p-value lower than 0.01. The same significant disparities were found for the percentages of Bax and Annexin V immunostaining (p<0.01 for each), reflecting the inflammation and apoptosis brought about by ischemia-reperfusion and the protective effects of the treatment. CONCLUSIONS: The outcomes of the current investigation showed that Silymarin could be a valuable agent for reducing testicular tissue damage following I/R injury. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a powerful chemotherapeutic agent used in many types of malignancies. However, its use results in testicular damage. DOX-induced testicular damage results in low level of serum testosterone which may affect cognitive function. The current study investigated the protective effect of liraglutide (50, 100 μg/kg/day) in testicular toxicity and the consequent cognitive impairment induced by DOX. DOX treatment reduced sperm count (62%) and sperm motility (53%) and increased sperm abnormalities (786%), as compared to control group. DOX also reduced serum testosterone level (85%) and the gene expression of testicular 3β-HSD (68%) and 17β-HSD (82%). Moreover, it increased testicular oxidative stress (MDA and GSH) by 103% and 59%, respectively, apoptotic (caspase-3 and P53) by 996% and 480%, respectively. In addition, DOX resulted in increasing autophagic markers including PAKT, mTOR, and LC3 by 48%, 56%, and 640%, respectively. Additionally, rats' behavior in Y-maze (60%) and passive avoidance task (85%) was disrupted. The histopathological results of testis and brain supported the biochemical findings. Treatment with liraglutide (100 μg/kg/day) significantly abrogated DOX-induced testicular damage by restoring testicular architecture, increasing sperm count (136%) and sperm motility (106%), and decreasing sperm abnormalities (84%) as compared to DOX group. Furthermore, liraglutide increased serum testosterone (500%) and steroidogenesis enzymes 3β-HSD (105%) and 17β-HSD (181%) along with suppressing oxidative stress (MDA and GSH) by 23% and 85%, respectively; apoptotic (caspase-3 and P53) by 59% and55%, respectively; and autophagic markers including PAKT, mTOR, and LC3 by 48%, 97%, and 60%, respectively. Moreover, it enhanced the memory functions in passive avoidance and Y-maze tests (132%). In conclusion, liraglutide is a putative agent for protection against DOX-induced testicular toxicity and cognitive impairment through its antioxidant, antiapoptotic, and antiautophagic effects. [ABSTRACT FROM AUTHOR]

Objectives: Methotrexate (MTX) is commonly used in the management of several malignancies and autoimmune disorders; however, testicular damage is one of the most detrimental effects of MTX administration. The current the protective effect of xanthine oxidase inhibitors either purine analogue; allopurinol (ALL) or non-purine analogue; febuxostat (FEB) in testicular injury induced by MTX in rats. Materials and methods: Thirty-two rats were randomly allocated to four groups; control (received vehicles), MTX (received single dose, 20 mg/kg, i.p.), MTX + ALL (received MTX plus ALL) and MTX + FEB (received MTX plus ALL). ALL and FEB were administered orally at 100- and 10 mg/kg, respectively for 15 days. Total and free testosterone were measured in serum. In addition, total antioxidant capacity (TAC), epidermal growth factor (EGF), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), extracellular signal-regulating kinase1/2 (ERK1/2), and total nitrite/nitrate (NOx) end products were measured in testicular tissues. At the same time, immunoexpression of HO-1in testicular tissue was measured. Histopathological examination was done. Results: ALL and FEB increased total and free serum testosterone. Both drugs showed a significant reduction in testicular MDA, NOx, TNF-α levels with an increase in TAC, EGF, and ERK1/2 levels in testicular tissue. Furthermore, both drugs enhanced HO-1 immunoexpression in testicular tissue. All these findings were parallel to the preservation of normal testicular architecture in rats treated with ALL and FEB. Conclusion: All and FEB were equally protective against testicular damage induced by MTX through anti-inflammatory, anti-apoptotic, and antioxidant actions. Their effects might be through activation of the EGF/ERK1/2/HO-1 pathway. [ABSTRACT FROM AUTHOR]

This study was carried out to investigate the protective properties of royal jelly on the testicular tissue of rats with testicular damage by giving fluoride. Sperm motility, epididymal sperm density and abnormal sperm ratios were examined and visualized with a light microscope. Expression levels of Caspase-3, Bcl-2, Nrf-2, NF-κB, COX-2, TNF-α and IL1-α proteins in testis tissue were determined by western blot technique. As a result of the study, MDA level, expression level of Bcl-2, NFҡB, COX-2, TNF-α and IL1-α proteins, abnormal sperm rates were found higher in Fluoride-50 and Fluoride100 groups compared to other groups. In addition GSH, Catalase enzyme levels, expression levels of Caspase-3 and Nrf-2 proteins were found to be higher in Fluoride + Royal Jelly groups compared to Fluoride-50 and Fluoride-100 groups. In addition, lower degeneration of testicular tissue was found in the histological evaluation in the Fluoride + Royal Jelly groups compared to the other groups. When the data are evaluated royal jelly provides effective protection against testicular damage. From this point of view, we hope that similar results will be obtained when royal jelly is tested on humans. [ABSTRACT FROM AUTHOR]

The objective of present study is to identify the adverse effects of cyclosporine A drug and the protective role of garlic in cytotoxicity test, including sperms deformation and histological changes in testes tissues of male albino rats. The study recorded significant increase p≥0.05 in sperms head and tail deformation rates in groups that were administrated cyclosporine and cyclosporine + garlic for two weeks compared with control groups which were administrated olive oil and garlic. The study reported significant decrease p≥0.05 in sperms head and tail deformation rates in the group that was administrated cyclosporine + garlic compared with group that was administrated cyclosporine only. In addition, the study also indicated histological changes in testes tissues including degenerative changes represented by depletion of the spermatogonial cells (some seminiferous tubules appeared with one or two layers of spermatogonia) in the group that was administrated cyclosporine compared with the control group which was administrated olive oil. The study reported slight histological changes in testes tissues from normal testes architecture, somniferous tubules with maturation of spermatogony and sperms inside the lumen in group that was administrated cyclosporine + garlic for two weeks compared with the control group which was administrated olive oil and garlic. Finally, the findings showed reduction in histological changes of testes tissues in group which was administrated cyclosporine + garlic for two weeks compared with group which was administrated cyclosporine only. [ABSTRACT FROM AUTHOR]

The goals of this study were to determine whether contrast-enhanced ultrasound (CEUS) imaging could be used for assessment of chronic alcohol-induced testicular damage (CAITD) and to explore the relationships between the laboratory and pathological findings of CAITD and the quantitative parameters of CEUS. Thirty-six rabbits were randomly divided into a chronic ethanol exposure (CEE) group and negative control (NC) group, which were further randomly divided into six groups with equal numbers of rabbits by period of exposure (30 d, 60 d, 90 d). All rabbits underwent conventional US and CEUS imaging at the end of the induction period. Blood and histological specimens were collected for laboratory and pathological examination. The peak intensity (PI) and area under the curve (AUC) for the CEUS parameters decreased as CAITD progressed (p < 0.05). Both PI and AUC were positively correlated with the Johnsen score (r = 0.945 and 0.898, respectively, all p values <0.001) and the mean epithelium thickness of the seminiferous tubule (METST) (r = 0.927 and 0.881, respectively, all p values <0.001) of the testis, and negatively correlated with the serum levels of endothelin-1 (ET-1) (r = –0.940 and –0.899, respectively, all p values <0.001) and nitric oxide (NO) (r = –0.894 and –0.954, respectively, all p values <0.001), as well as the testicular tissue content of malondialdehyde (MDA) (r = –0.894 and –0.945, respectively, all p values <0.001). CEUS imaging can be used for monitoring organ perfusion of the testis to quantify the development of CAITD. [ABSTRACT FROM AUTHOR]

Varicocele is a pathological dilation of the venous network of the spermatic cord and considering that magnesium oxide nanoparticles play a key role in various physiological functions, the aim of this study was to evaluate the performance of nanoparticles on sperm characteristics affected by experimental varicocele. A total of 54 male Wistar rats were randomly divided into 9 equal groups including healthy control group (untouched animals), sham-operated group (underwent sham surgery), three healthy experimental groups (animals in these groups received magnesium oxide nanoparticles at doses of 1.25, 2.5 and 5 mg/kg respectively by gavage for 6 weeks), varicocele control group (varicocele was induced by renal vein ligation) and three experimental varicocele groups (in addition to varicocele induction, magnesium oxide nanoparticles were given at doses of 1.25, 2.5 and 5 mg/kg respectively by gavage for 6 weeks). At the end of the 6th week, the abdomen was opened and semen samples were collected from the tail of the epididymis to determine the indices of concentration, survival and motility of sperm and the data were statistically analyzed (p

Aim: The toxic effects of methotrexate, a chemotherapeutic, on the testicles is an important side effect. Methotrexate impairs spermatogenesis and fertility and causes oligospermia. In this study, we aimed to minimize the testicular toxicity, those being the side effects of methotrexate, by using the probable protective effects of α-lipoic acid, a potent antioxidant. Materials and Methods: Twenty-eight male Sprague Dawley rats that we employed in this research were separated into three groups as control (0.09% PS) (n=8), methotrexate (20 mg/kg) (n= 10), and methotrexate (20 mg/kg) + α-lipoic acid (100 mg/kg) (n= 10). We performed a histochemical analysis on the testicular tissue of rats using hematoxylin-eosin and Masson’s trichrome. We performed an immunohistochemical analysis using inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) primer ab. Results: The histochemical evaluation revealed a significant decrease in the methotrexate-induced testicular toxicity in the α-lipoic acid-treated groups. On the other hand, TNF-α and iNOS immunostaining results were also observed to support these results. Conclusion: The treatment use of α-lipoic acid succeeded in protecting against methotrexate-induced testicular damage through an α-lipoic acid-mediated antioxidant and anti-inflammatory mechanisms. α-lipoic acid can be used in combination with methotrexate as a protector against side effects during anticancer therapy. In the present study, it was shown that α-lipoic acid can be used in combination with methotrexate as a protector against side effects during anticancer treatment.

Abstract Background Zika virus (ZIKV) infection is clinically known to induce testicular swelling, termed orchitis, and potentially impact male sterility, but the underlying mechanisms remain unclear. Previous reports suggested that C-type lectins play important roles in mediating virus-induced inflammatory reactions and pathogenesis. We thus investigated whether C-type lectins modulate ZIKV-induced testicular damage. Methods C-type lectin domain family 5 member A (CLEC5A) knockout mice were generated in a STAT1-deficient immunocompromised background (denoted clec5a −/− stat1 −/− ) to enable testing of the role played by CLEC5A after ZIKV infection in a mosquito-to-mouse disease model. Following ZIKV infection, mice were subjected to an array of analyses to evaluate testicular damage, including ZIKV infectivity and neutrophil infiltration estimation via quantitative RT-PCR or histology and immunohistochemistry, inflammatory cytokine and testosterone detection, and spermatozoon counting. Furthermore, DNAX-activating proteins for 12 kDa (DAP12) knockout mice (dap12 −/− stat1 −/− ) were generated and used to evaluate ZIKV infectivity, inflammation, and spermatozoa function in order to investigate the potential mechanisms engaged by CLEC5A. Results Compared to experiments conducted in ZIKV-infected stat1 −/− mice, infected clec5a −/− stat1 −/− mice showed reductions in testicular ZIKV titer, local inflammation and apoptosis in testis and epididymis, neutrophil invasion, and sperm count and motility. CLEC5A, a myeloid pattern recognition receptor, therefore appears involved in the pathogenesis of ZIKV-induced orchitis and oligospermia. Furthermore, DAP12 expression was found to be decreased in the testis and epididymis tissues of clec5a −/− stat1 −/− mice. As for CLEC5A deficient mice, ZIKV-infected DAP12-deficient mice also showed reductions in testicular ZIKV titer and local inflammation, as well as improved spermatozoa function, as compared to controls. CLEC5A-associated DAP12 signaling appears to in part regulate ZIKV-induced testicular damage. Conclusions Our analyses reveal a critical role for CLEC5A in ZIKV-induced proinflammatory responses, as CLEC5A enables leukocytes to infiltrate past the blood-testis barrier and induce testicular and epididymal tissue damage. CLEC5A is thus a potential therapeutic target for the prevention of injuries to male reproductive organs in ZIKV patients.

Despite being a potent anticancer drug, cisplatin has limited applicability due to its adverse effects, such as testicular damage. Consequently, reducing its toxicity becomes necessary. In this study, a selective phosphodiesterase-3 inhibitor, cilostazol, which is used to treat intermittent claudication, was examined for its ability to abrogate cisplatin-induced testicular toxicity. Its ameliorative effect was compared to that of two phosphodiesterase inhibitors, tadalafil and pentoxifylline. The study also focused on the possible mechanisms involved in the proposed protective effect. Cisplatin-treated rats showed a significant decrease in sperm number and motility, serum testosterone, and testicular glutathione levels, as well as a significant elevation in malondialdehyde, total nitrite levels, and the protein expression of tumor necrosis factor-alpha, nuclear factor-kappa β, and caspase-3. These outcomes were confirmed by marked testicular architecture deterioration. Contrary to this, cilostazol, in a dose-dependent manner, showed potential protection against testicular toxicity, reversed the disrupted testicular function, and improved histological alterations through rebalancing of oxidative stress, inflammation, and apoptosis. In addition, cilostazol exerted a more pronounced protective effect in comparison to tadalafil and pentoxifylline. In conclusion, cilostazol ameliorates cisplatin-induced testicular impairment through alteration of oxidative stress, inflammation, and apoptotic pathways, offering a promising treatment for cisplatin-induced testicular damage. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is a chemotherapeutic medicine frequently used to treat various forms of cancer. The objective of our research was to examine whether allicin (ALC) and lycopene (LP) could alleviate the harmful effects of MTXinduced testicular toxicity in rats. A total of 49 male white albino rats were divided into 7 groups (7 rats in each group). The rats of group 1 was kept as a control group and received normal saline orally; while rats of group 2 and group 3 administered ALC (20mg/kg/BW) LP (10mg/kg/BW) orally. On day 15, the rats of group 4 received a single dose of MTX (20mg/kg, IP). In group 5, rats received ALC and MTX; in group 6, rats received LP and MTX, and in group 7, rats received ALC, LP, and MTX. Results showed that MTX induced significant increase in values of testicular malondialdehyde (MDA) levels with a substantial reduction in glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and lowered the serum testosterone, follicle-stimulating hormone (FSH), and lutenizing hormone (LH) levels. MTX induced a marked decline in seminiferous tubule diameter and epithelium height. MTX showed a widening of the interstitial space of seminiferous tubules, atrophy, vacuolar degeneration of the germinal epithelium and Leydig's interstitial cells had scanty cytoplasm and vesicular nuclei. Also, testicular proliferating cell nuclear antigen (PCNA) expression was recorded. In MTX-intoxicated rats, ALC and LP increased antioxidant biomarkers, decreased MDA, and attenuated changes in serum hormonal parameters. It is concluded that ALC and LP have significant protective effects on MTX- induced testicular toxicity due to their antioxidant properties. [ABSTRACT FROM AUTHOR]

Paraquat (PQ) is an organic compound, which is commonly used as a herbicide in the agriculture sector, and it is also known to stimulate critical damages in the male reproductive system. Gossypetin (GPTN) is one of important members of the flavonoid family, which is an essential compound in flowers and calyx of Hibiscus sabdariffa with potential pharmacological properties. The current investigation was aimed to examine the ameliorative potential of GPTN against PQ-instigated testicular damages. Adult male Sprague–Dawley rats (n = 48) were distributed into four groups: control, PQ (5 mg/kg), PQ + GPTN (5 mg/kg + 30 mg/kg respectively), and GPTN (30 mg/kg). After 56 days of treatment, biochemical, spermatogenic indices, hormonal, steroidogenic, pro-or-anti-apoptotic, and histopathological parameters were estimated. PQ exposure disturbed the biochemical profile by reducing the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GSR), while it increased the concentration of reactive oxygen species (ROS) and malondialdehyde (MDA) level. Furthermore, PQ exposure decreased the sperm motility, viability, number of hypo-osmotic tail swelled spermatozoa, and epididymal sperm count; additionally, it increased sperm morphological (head mid-piece and tail) abnormalities. Moreover, PQ lessened the follicle-stimulating hormone (FSH), luteinizing hormone (LH), and plasma testosterone levels. Besides, PQ-intoxication downregulated the gene expression of steroidogenic enzymes (StAR, 3β-HSD, and 17β-HSD) and anti-apoptotic marker (Bcl-2), whereas upregulated the gene expression of apoptotic markers (Bax and Caspase-3). PQ exposure led to histopathological damages in testicular tissues as well. Nonetheless, GPTN inverted all the illustrated impairments in testes. Taken together, GPTN could potently ameliorate PQ-induced reproductive dysfunctions due to its antioxidant, androgenic, and anti-apoptotic potential. [ABSTRACT FROM AUTHOR]

The current study aimed to identify the adverse effects of azithromycin drug and the protective role of garlic in cytotoxicity tests that included sperm deformation and histological changes in testes tissue of male albino rats. Twenty-four mature male rat animals (Rattus norvegicus) were used in the present study, their age was (2.5 – 3) months, and their weight ranged from 148 to 280 gm they were divided into four groups as follows: The first group was the control group contained four rats and was administered distilled water only. In contrast, the second group containing four rats was administered garlic at 480 mg/kg body weight. The third group included eight rats, was administered Azithromycin at the dose of 500 mg/kg body weight. The fourth group contained eight rats, and Azithromycin was administrated at 500 mg/k mg+ garlic at 480 mg/kg body weight. The groups were treated with Azithromycin and garlic daily. The results recorded a significant increase (p ≥0.05) in sperm head and tail deformation rate in the group administered Azithromycin + garlic compared with the control groups that were administrated distilled water and garlic. Furthermore, the results reported a significant decrease (p≥0.05) in sperm head and tail deformation rates in the group administered Azithromycin + garlic compared with the only Azithromycin administered group. Moreover, the study indicated histological changes in testes tissue included degenerative changes represented by depletion of the spermatogonial cells (some seminiferous tubules appeared with one or two layers of spermatogonia) in the group that was administered Azithromycin compared with the control group, which was administered distilled water and garlic. In addition, the study indicated slight histological changes in testes tissue compared with standard testes architecture, somniferous tubules with the maturation of spermatogony, and sperms inside the lumen in groups administered Azithromycin and garlic compared with control groups, which were administered distilled water and garlic Finally, the findings showed a reduction in histological changes in testes tissue in the group that was administered azithromycin+garlic compared with the group that was administered Azithromycin only. [ABSTRACT FROM AUTHOR]