In vivo Gonadoprotective Effects of Myricetin on Cisplatin- Induced Testicular Damage via Suppression of TLR4/NF-kB Inflammation Pathway and Heat-Shock Response / Efectos Gonadoprotectores in vivo de la Miricetina sobre el Daño Testicular Inducido por Cisplatino Mediante la Supresión de la Vía de Inflamación TLR4/NF-kB y la Respuesta al Choque Térmico

SUMMARY: 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.

El objetivo de este estudio es revelar los efectos gonadoprotectores de la miricetina (MYC), que tiene muchas propiedades biológicas, sobre el daño testicular inducido por cisplatino (CP) en ratas. Para este propósito, se dividieron 40 ratas albinas Wistar macho en 4 grupos: Control (grupo que no recibió tratamiento), MYC (grupo que recibió 5 mg/kg/i.p de miricetina durante 7 días), CP (grupo que recibió 7 mg/kg/i.p de cisplatino al séptimo día) y MYC + CP (grupo que recibió 5 mg/ kg/i.p de miricetina durante 7 días antes de la inyección de 7 mg/ kg/i.p de cisplatino). Después de las administraciones, se extrajeron y procesaron tejidos testiculares de animales según el protocolo de procesamiento de tejidos. Se realizó tinción con hematoxilina y eosina para evaluar los cambios histopatológicos y se aplicó la puntuación de biopsia testicular de Johnsen (JTBS) y se midieron los diámetros medios de los túbulos seminíferos (MSTD) para comparar los grupos experimentales en términos de cambios histopatológicos. Además, los niveles de expresión de TLR4, NF-kB, HSP70 y HSP90 se detectaron mediante tinción inmunohistoquímica y se midió la densidad de inmunorreactividad para determinar la diferencia en los niveles de expresión de estos factores entre los grupos. Además, se detectó apoptosis testicular mediante el ensayo TUNEL. Los datos de JTBS y MSTD fueron significativamente más bajos en el grupo CP en comparación con otros grupos y las administraciones de MYC protegen significativamente el tejido testicular contra el daño inducido por CP. Además, las expresiones de TLR4, NF-kB, HSP70 y HSP90 y las células apoptóticas aumentaron significativamente en el grupo CP (p<0,05). Sin embargo, las administraciones de MYC ejercieron un fuerte efecto gonadoprotector sobre el tejido testicular en términos de estos parámetros en el grupo MYC+CP (p<0,05). Según nuestros resultados, sugerimos que MYC puede considerarse como un agente protector contra el daño testicular inducido por cisplatino.

Fatal motorcycle straddle injury consolidated with traumatic testicular dislocation: A case report.

Straddle injuries are those to the perineum region brought on by straddling or riding over something, such as a horse, vehicle, or other object. The motorcycle fuel tank or handlebars are primarily responsible for the typical injury to the perineum area in motorcycle accidents. Motorcycle straddle injury usually manifest as abrasions to the scrotum or penis, and severe cases can cause pelvic fractures or even testicular dislocation. Because these injuries are usually closed with unclear internal damage, diagnosis presents a significant challenge and can easily lead to misdiagnosis. However, pelvic fractures and the bleeding and nerve damage associated with perineal injury are often fatal, and testicular dislocation can also have serious consequences for patients. Therefore, a clear diagnosis and timely treatment are crucial for patients with this type of injury. This article reports the case of a motorcycle rider who died 4 h after a traffic accident with only minor surface injury visible, showing only bruising in the waist and scrotum. A forensic examination revealed multiple fractures throughout the patient's body, with a slightly more severe pelvic fracture and testicular dislocation on the left side in the left inguinal area. This article analyzes the cause of death and related issues in this case, aiming to provide assistance to clinical physicians and forensic practitioners and to emphasize the importance of handling straddle injury in treatment and related investigations to avoid serious consequences.

Traumatic testicular dislocation in the abdomen: diagnosis and management.

Testicular dislocation in the abdomen after scrotal trauma is a rare and sometimes unrecognised event.Early detection and timely management reduce possible complications which include the risk of fertility loss, endocrine dysfunction, and future malignancy.We present the case of a man who suffered a traumatic dislocation of the right testis in the abdomen after a motorcycle crash. The large scrotal haematoma did not permit adequate physical examination. Furthermore, during the clinical management of the polytrauma, the main focus was on active arterial bleeding, multiple pelvic fractures and clinical investigation of the integrity of the lower urinary tract. Therefore, the diagnosis and surgical management of the testicular dislocation were delayed.The patient underwent abdominal-inguinal surgical exploration, haematoma evacuation, identification of the right testis and right orchidopexy.After 6 months, the right testis of the patient is of regular volume, consistency and physiologic echogenicity on ultrasound evaluation.Hormonal evaluation and semen analysis were normal after 3 months.

Tunica Vaginalis Graft Use for Repair of Traumatic Testicular Rupture: A Case Report.

Testicular rupture is a rare but serious condition which requires immediate and emergent surgical intervention in order to preserve fertility and maintain gonadal hormone function. We present here a case of a 16-year-old male who suffered a shattered right testicle following gunshot wound. Additionally, the left cord structures were also hit with possible compromise of the left testicle. He underwent scrotal exploration with reconstruction of the right tunica albuginea with a tunica vaginalis graft. The right testicle was found to be viable within 2months postoperatively with normal arterial and venous flow seen on Doppler scrotal ultrasound. We propose that tunica vaginalis can be used successfully as a graft to manage testicular rupture.

A Rare and Easily Overlooked Case of Bilateral Traumatic Testicular Dislocation and an Alternative Viewpoint on Delayed Management.

The incidence of traumatic testicular dislocation is rare, and it is usually overlooked in an initial diagnosis. We present a case of bilateral dislocated testes after a traffic accident that was treated via orchidopexy one week later. No testicular complications had occurred by the time of the follow-up visit. Generally, surgery is often postponed owing to a late diagnosis or another major organ injury, and the adequate timing of surgery is still under debate. We performed a review of past cases, which showed similar testicular outcomes irrespective of surgical timing. Delayed intervention may be a feasible decision after a patient's hemodynamic status is stable for surgery. To prevent delayed diagnosis, scrotal examination should not be overlooked in any patients presenting with pelvic trauma to the emergency department.

Testicular torsion and subsequent testicular function in young men from the general population.

STUDY QUESTION: Is prior testicular torsion associated with testicular function (semen quality and reproductive hormones) in young men from the general population? SUMMARY ANSWER: In young men from the general population, no differences in semen parameters were observed in those who had experienced testicular torsion compared to controls and observations of higher FSH and lower inhibin B were subtle. WHAT IS KNOWN ALREADY: Testicular function may be impaired after testicular torsion, but knowledge is sparse and based on studies with small sample sizes and no control group or a less than ideal control group. STUDY DESIGN, SIZE, DURATION: A cross-sectional population-based study was carried out including 7876 young Danish men with unknown fertility potential, examined from 1996 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: All men (median age 19.0 years) had a physical examination, provided a blood and semen sample, and filled in a questionnaire including information about prior testicular torsion, birth, lifestyle and current and previous diseases. Markers of testicular function, including testis volume, semen parameters and reproductive hormones, were compared between men operated for testicular torsion and controls, using multiple linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The average participation rate was 24% for the entire study period. In total, 57 men (0.72%) were previously operated for testicular torsion (median age at surgery 13.4 years) of which five had only one remaining testicle. Men with prior testicular torsion were more often born preterm (25% versus 9.5% among controls), and they had significantly higher FSH and lower inhibin B levels, and a lower inhibin B/FSH ratio than controls in crude and adjusted models. The association was mainly driven by the subgroup of men who had undergone unilateral orchiectomy. No differences in semen parameters were observed. LIMITATIONS, REASONS FOR CAUTION: A limitation is the retrospective self-reported information on testicular torsion. Also, results should be interpreted with caution owing to the high uncertainty of the observed differences. WIDER IMPLICATIONS OF THE FINDINGS: Overall, the results of our study are reassuring for men who have experienced testicular torsion, especially when treated with orchiopexy, for whom reproductive hormone alterations were subtle and without obvious clinical relevance. Our study found no differences in semen parameters, but follow-up studies are needed to assess any long-term consequences for fertility. STUDY FUNDING/COMPETING INTEREST(S): Financial support was received from the Danish Ministry of Health; the Danish Environmental Protection Agency; the Research fund of Rigshospitalet, Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603, FP7/2007-2013, DEER Grant agreement no. 212844); A.P. Møller and wife Chastine Mckinney Møllers Foundation; Svend Andersens Foundation; the Research Fund of the Capital Region of Denmark; and ReproUnion (EU/Interreg). The authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Bone marrow mesenchymal stem cells repair hexavalent chromium-induced testicular injury by regulating autophagy and ferroptosis mediated by the AKT/mTOR pathway in rats.

There is no ideal therapy for testicular damage induced by Cr(VI); however, bone marrow mesenchymal stem cells (BMSCs) transplantation may be a promising therapy. A Cr(VI) solution was administered to rats by intraperitoneal injection for 30 days, then BMSCs from donor rats were transplanted. Two weeks later, decreased activity and appetite, along with other pathological changes, were improved in the BMSCs group. The location of BMSCs in damaged testes was observed via laser confocal microscopy. Chromium content in the Cr(VI) and BMSCs groups significantly increased compared with that in the control group, but there was no significant difference between the two groups, as revealed by atomic absorption spectrometry. The ferrous iron and the total iron content of testes in the BMSCs group were significantly lower than those in the Cr(VI) group, as observed by Lillie staining and a tissue iron assay kit. Western blotting and immunohistochemical analyses revealed that the expression of Beclin 1, LC3B, 4-hydroxynonenal, and transferrin receptor 1 was decreased in the BMSCs group, compared with the Cr(VI) group. The expression of glutathione peroxidase 4 (GPX4), SLC7A11, p-AKT, mammalian target of rapamycin (mTOR), and p-mTOR in the BMSCs group was higher than that in the Cr(VI) group. Taken together, we propose that BMSCs repair Cr(VI)-damaged testes by alleviating ferroptosis and downregulating autophagy-associated proteins through the upregulation of AKT and mTOR phosphorylation.

The effect of taxifolin on experimental testicular ischaemia reperfusion injury in rats. A biochemical and histopathological analysis / Efecto de la taxifolina en la lesión experimental testicular por reperfusión-isquemia en ratas. Análisis bioquímico e histopatológico

Objectives: The aim of the study is to investigate the protective effect of taxifolin (3,5,7,3,4-pentahydroxy flavanone), a strong antioxidant, against testicular I/R injury in rats biochemically and histopathologically.Materials and methods: 50mg/kg taxifolin was administered to taxifolin+testicular torsion–detorsion (TTTD, n-10) group of Albino Wistar male rats by oral gavage. Distilled water .5ml as a solvent was administered to testicular torsion–detorsion (TTD, n-10) and Healthy Control (SG, n-10) groups using the same method. An hour after the administration of taxifolin and distilled water, anaesthesia (ketamine 60mg/kg) was administered to all animal groups. TTD and TTTD group animals were subjected to testicular torsion at 720 degrees for four hours during anaesthesia. At the end of this period, testicular detorsion was applied and perfusion was allowed for four hours. Sham operation was applied to SG group.Results: Our biochemical experiment results showed that the amount of malondialdehyde (MDA) in testicular tissue of TTD group presented a significant increase compared to SG and TTTD groups whereas total glutathione (tGSH) and superoxide dismutase (SOD) levels decreased. In addition, while TTD group presented severe histopathological damage in germinal epithelium cell and seminiferous tubule, mild damage was observed in TTTD group.Conclusions: The results of our experiment indicate that taxifolin could be useful in the treatment of testicular I/R damage. (AU)

Objetivos: El objetivo del estudio fue analizar el efecto protector de la taxifolina (3,5,7,3,4-pentahidroxi flavanona), un fuerte antioxidante, en la lesión por reperfusión-isquemia (R/I) en ratas, a nivel bioquímico e histopatológico.Materiales y métodos: Se administraron 50 mg/kg de taxifolina a un grupo de ratas macho Albino Wistar con torsión-destorsión y taxifolina+testicular (TTTD, n-10) mediante una sonda oral, y una solución de 0,5 mL de agua destilada a un grupo con torsión-destorsión testicular (TTD, n-10) y a controles sanos (SG, n-10), utilizando el mismo método. Una hora después de la administración de taxifolina y agua destilada, se aplicó anestesia (ketamina 60 mg/kg) a todos los grupos de animales. Los grupos TTD y TTTD fueron sometidos a una torsión testicular a 720 grados por cuatro horas durante la anestesia. Al finalizar este período, se aplicó destorsión testicular, permitiéndose la perfusión durante cuatro horas. Se aplicó un placebo al grupo SG.Resultados: Los resultados de nuestro experimento bioquímico reflejaron que el incremento de malondialdehído (MDA) en el tejido testicular del grupo TTD presentó un aumento significativo en comparación con los grupos SG y TTTD, mientras que disminuyeron los niveles de glutatión (tGSH) y superóxido dismutasa (SOD). Además, mientras que el grupo TTD presentó daño histopatológico severo en las células del epitelio germinal y el tubo seminífero, se observó un daño leve en el grupo TTTD.Conclusiones: Los resultados de nuestro experimento indican que la taxifolina podría ser de utilidad para el tratamiento de la lesión testicular por R/I. (AU)

Natural products against cisplatin-induced male reproductive toxicity: A comprehensive review.

Cisplatin is widely used as one of the most effective anticancer agents in the treatment of some neoplasms. Reproductive toxicity is the most common outcome associated with cisplatin testicular damage. Alternative natural medicines for treating male testicular disorders and infertility have received extensive attention in research. Natural products, medicinal herbs, and their secondary metabolites have been shown as promising agents in the management of testicular damage induced by chemotherapy drugs. This study aimed to review the research related to natural substances that are promising in mitigation of the cisplatin-induced toxicity in the reproductive system. PubMed and Scopus were searched for studies on various natural products for their potential protective property against reproductive toxicity induced by cisplatin from 2000 to 2020. Eligibility was checked based on selection criteria. Fifty-nine articles were included in this review. Mainly in animal studies, several natural agents have positively affected cisplatin-reproductive-toxicity factors, including reactive oxygen species, inflammatory mediators, DNA damage, and activation of the mitochondrial apoptotic pathway. Most of the natural agents were investigated in short-term duration and high doses of cisplatin exposure, considering their antioxidant activity against oxidative stress. Considering antioxidant properties, various natural products might be effective for the management of cisplatin reproductive toxicity. However, long-term recovery of spermatogenesis and management of low-dose-cisplatin toxicity should be considered as well as the bioavailability of these agents before and after treatment with cisplatin without affecting its anticancer activity.

Caffeic acid phenethyl ester mitigates infertility: A crucial role of metalloproteinase and angiogenic factor in cadmium-induced testicular damage.

Cadmium (Cd) is expected to cause deleterious effects on most organs, especially on the male reproductive system. The current study was performed to assess the effect of Cd on fertility in Swiss mice and to evaluate the protective role of caffeic acid phenethyl ester (CAPE) in relieving the detrimental effect of Cd. The mice were divided into four groups of 10: normal Group I received distilled water. Group II, III, and IV were injected 3 mg/kg body weight with Cd intraperitoneally for four consecutive days. Group III received saline. Group IV was treated with 3 mg/kg/day CAPE intraperitoneally for 6 days. Results indicated that CAPE brings about a highly significant improvement in fertility parameters, spermatogenesis, and reduced apoptotic percent. Moreover, metalloprotease-3 (MMP-3) and vascular endothelial growth factor reduced significantly. Overall, our results strongly suggest that CAPE has a protective effect, counteracts the toxic effects of Cd, and prevents testicular injury.

Mangiferin mitigates di-(2-ethylhexyl) phthalate-induced testicular injury in rats by modulating oxidative stress-mediated signals, inflammatory cascades, apoptotic pathways, and steroidogenesis.

Di-(2-ethylhexyl) phthalate (DEHP) is an endocrine disruptor that causes reproductive defects in male animal models. This study was conducted to explore the plausible modulatory effects of mangiferin (MF) against DEHP-induced testicular injury in rats. Thirty-two adult male albino rats were allocated into four groups. Two groups were given DEHP (2 g/kg/day, p.o) for 14 days. One of these groups was treated with MF (20 mg/kg/day, i.p) for 7 days before and 14 days after DEHP administration. A vehicle-treated control was included, and another group of rats was given MF only. Results revealed that MF treatment suppressed oxidative testicular injury by amplifying the mRNA expression of nuclear factor-erythroid 2 related factor-2 (Nrf2) and increasing hemoxygenase-1 (HO-1), glutathione, and total antioxidant capacity (TAC) levels. This treatment also enhanced superoxide dismutase activity, but it decreased malondialdehyde and nitric oxide levels. MF had an anti-inflammatory characteristic, as demonstrated by the downregulation of the mRNA of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The content of tumor necrosis factor-alpha also decreased. MF modulated the apoptotic pathway by suppressing the mRNA of cytochrome c (Cyt c), Fas ligand content, Bax IHC expression, caspase-3 activity and cleaved caspase-3 IHC expression. It also upregulated the expression levels of heat-shock protein 70 (HSP70) and B-cell lymphoma 2. Moreover, MF upregulated the mRNA expression levels of HSP70 and c-kit and enriched the content of steroidogenic acute regulatory (StAR) protein, which were reflected in serum testosterone levels. This result indicated that MF played crucial roles in steroidogenesis and spermatogenesis. Besides, the activities of testicular marker enzymes, namely, acid and alkaline phosphatases, and lactate dehydrogenase, significantly increased. Histopathological observations provided evidence supporting the biochemical and molecular measurements. In conclusion, MF provided protective mechanisms against the DEHP-mediated deterioration of testicular functions partially through its antioxidant, anti-inflammatory, and anti-apoptotic properties. It also involved the restoration of steroidogenesis and spermatogenesis through the modulation of Nrf2/HO-1, NF-κB/Cyt c/HSP70, and c-Kit signaling cascades.

Blunt Abdominopelvic Trauma Complicated by Traumatic Testicular Dislocation in a 19-Year-Old Male Patient: A Case Report.

CASE: A 19 year-old male patient presented with testicular dislocation after abdominopelvic trauma. During open reduction and internal fixation, consult to urology was placed after discovering the presence of the intra-abdominal testicle. The testicle was repositioned into the scrotum with orchiopexy, and pelvic fixation was completed with 1 sacroiliac percutaneous screw and pubic symphysis fixation. Postoperative recovery was uneventful, and the patient was discharged home on postoperative day 3. CONCLUSION: Testicular dislocation is an uncommon finding after blunt abdominopelvic trauma; hence, it may be overlooked. Prompt diagnosis of testicular dislocation given the need for operative management to preserve testicle viability is crucial.

DEHP-induced testicular injury through gene methylation pathway and the protective effect of soybean isoflavones in Sprague-Dawley rats.

As one of the most important members of Phthalate esters (PAEs), di-(2-ethylhexyl) phthalate (DEHP) is widely used in plastics and known as a male reproductive toxicant. Many studies have shown that soybean isoflavones (SI) can rescue the testicular injury caused by DEHP, but the underlying mechanism is unknown. Because methylation is one of the most important mechanisms for maintaining normal biological functions, we studied whether methylation is involved in testicular injury induced by DEHP and whether SI could counter testicular impairment in peripubertal male Sprague Dawley rats. Compared with the control group, we found that the mRNA levels of testicular Sod2, Gpx1, and Igf-1 significantly decreased in the 900 mg/kg DEHP group (DEHP' group) (P < 0.01); however, in the DEHP + SI group, the mRNA levels of the genes obviously increased compared with the DEHP' group (P < 0.01). Simultaneously, the methylation level changes of testicular Sod2, Gpx1, and Igf-1 were similar to the mRNA levels (P < 0.01). Therefore, DEHP may affect testis and leydig cells via inducing methylation of Sod2, Gpx1, and Igf-1, and SI may rescue the impairments at the methylation level. In summary, SI is supposed to be used in DEHP-induced testicular injury treatment.

Ameliorative Potential of Hydroethanolic Leaf Extract of Parquetina nigrescens on d-Galactose-Induced Testicular Injury.

BACKGROUND: There is an increasing need for botanicals to be used as an alternative and complementary medicine in the management of male infertility. Male infertility has been a major health/social challenge to people all over the world. This study, therefore, investigated the ameliorative potential of hydroethanolic leaf extract of Parquetina nigrescens (HELEPN) against d-galactose-induced testicular injury. METHODS: Thirty male Wistar rats were randomly allotted into six groups (n = 5). Group I (Normal control), Group II (300 mg/kg b.w. d-galactose), Group III and IV (250 and 500 mg/kg b.w. HELEPN, respectively), Group V and VI (both received 300 mg/kg b.w. of d-galactose with 250 and 500 mg/kg b.w of HELEPN, respectively). d-galactose administration started two weeks prior to HELEPN treatment which lasted for six weeks. All assays were carried out using established protocols. RESULTS: Administration of HELEPN at 250mg/kg and 500mg/kg concomitantly with d-galactose improved paired and relative testicular weights, levels of gonadotropins (LH and FSH) and testosterone, and poor sperm quality. HELEPN treatment reduced the levels of oxidative stress biomarkers (MDA, 8-OHDG, and AGEs) and inflammatory response (TNF-alpha and NO) to normal, as well as restoring the reduced activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase). In addition, HELEPN treatment mitigated testicular DNA fragmentation and down-regulated caspase 3-activities. HELEPN at 500 mg/kg was observed to have the greatest ameliorative effect. CONCLUSION: HELEPN protects against d-galactose-induced testicular injury through antioxidative, anti-inflammatory, and antiapoptotic mechanisms.

Quercetin Inhibits ROS-p53-Bax-caspase-3 axis of apoptosis and augments gonadotropin and testicular hormones in chronic unpredictable stress-Induced testis injury / La quercetina inhibe el eje de apoptosis ROS-p53-Bax-caspasa-3 y aumenta la gonadotropina y las hormonas testiculares en la lesión testicular inducida por estrés crónico e impredecible

SUMMARY: A large body of evidence supports the protective role of the flavonol antioxidant compound quercetin in mammals. We tested the hypothesis that quercetin can protect against the hypothalamus-pituitary-gonadal (HPG) axis defect like a reduction in gonadotropins and testicular hormones and abnormal semen analysis induced by chronic unpredictable stress (CUS), possibly via the downregulation of oxidative stress (ROS) and p53-Bax-caspase-3 pathways. Rats were either exposed to a variety of unpredictable stressors daily before being sacrificed after 3 weeks (model group) or were treated with quercetin (50 mg/kg body weight/day) at the same time the CUS were induced (treated group). Harvested testicular tissues were stained with basic histological staining, and testis homogenates were assayed for the tumor suppressor p53, apoptosis regulator Bax, B-cell lymphoma 2 (Bcl-2), caspase-3, malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, harvested epididymis tissues were used to assess semen analysis, and blood samples were assayed for the testicular hormone testosterone, the adrenal cortex hormone corticosterone, and the anterior pituitary gonadotropins, follicular stimulating hormone (FSH) and luteinizing hormone (LH). CUS induced profound testicular damage and significantly (p<0.05) induced p53, Bax, caspase-3, MDA, and corticosterone, which were significantly (p<0.05) inhibited by quercetin except corticosterone. Whereas, quercetin significantly (p<0.05) increased FSH, LH, testosterone, Bcl-2, GPx, and SOD levels that were inhibited by CUS. In addition, CUS induced oligozoospermia, asthenozoospermia, and teratozoospermia, which were significantly (p<0.05) protected by quercetin. Thus, Quercetin protects against CUS-induced HPG defects in rats, which is associated with the inhibition of ROS-p53-Bax-caspase-3 axis.

RESUMEN: El papel protector del compuesto antioxidante flavonol quercetina en los mamíferos ha sido ampliamente reportado. Probamos la hipótesis que la quercetina puede proteger contra el defecto del eje hipotálamo-hipofisiario- gonadal (HHG) como una reducción de gonadotropinas y hormonas testiculares y análisis de semen anormal inducido por estrés crónico impredecible (ECI), posiblemente a través de la regulación reducida del estrés oxidativo (REO) y las vías p53- Bax-caspasa-3. Las ratas fueron expuestas a una variedad de fac- tores estresantes impredecibles diariamente antes de ser sacrificadas después de 3 semanas (grupo modelo) o fueron tratadas con quercetina (50 mg / kg de peso corporal / día) al mismo tiempo que se indujo la ECI (grupo tratado). Los tejidos testiculares fueron teñidos con tinción histológica básica y los homogeneizados de testículo se analizaron para determinar el supresor de tumores p53, el regulador de apoptosis Bax, el linfoma de células B 2 (Bcl-2), la caspasa-3, el malondialdehído (MDA), la glutatión peroxidasa (GPx) y superóxido dismutasa (SOD). Además, se utilizaron tejidos del epidídimo recolectados para evaluar el análisis de semen y se analizaron muestras de sangre para determinar la hormona testicular testosterona, la hormona corticosterona de la corteza suprarrenal y las gonadotropinas de la hipófisis anterior, la hormona estimulante folicular (FSH) y la hormona luteinizante (LH). El ECI indujo daño testicular importante e indujo significativamente niveles de (p <0,05) p53, Bax, caspasa-3, MDA y corticosterona, que fueron inhibidos (p <0,05) por la quercetina. La quercetina aumentó significativamente (p <0,05) los niveles de FSH, LH, testosterona, Bcl-2, GPx y SOD que fueron inhibidos por ECI. Además, ECI indujo oligozoospermia, astenozoospermia y teratozoospermia, protegidos de manera significativa (p <0,05) por la quercetina. Por lo tanto, la quercetina protege contra los defectos de HHG inducidos por ECI en ratas, lo que está asociado con la inhibición del eje ROS-p53-Bax-caspasa-3.

Tranilast abrogates cisplatin-induced testicular and epididymal injuries: An insight into its modulatory impact on apoptosis/proliferation.

Cisplatin is a chemotherapeutic agent whose therapeutic use is greatly limited by the associated organs' toxicity and particularly, testicular toxicity. Cisplatin-induced testicular damage reported being mediated through mitochondria-mediated apoptosis, inflammation, and oxidative stress. Evidence showed that tranilast (TRN) has the ability to restore the oxidative status and modulate TRAIL/caspase-8 signaling. This led us to hypothesize that TRN could abrogate cisplatin-induced testicular and epididymal injuries via inhibiting oxidative stress and modulating proliferation and TRAIL/caspase-8/cJNK signaling. Cisplatin injection induced oligospermia and abnormalities in testicular and epididymal structure along with impaired oxidative status. TRN administration (100 or 300 mg/kg) for 7 days post-cisplatin injection preserved spermatogenesis and restored testicular and epididymal architecture, but restoration was more so in TRN300 than TRN100. This was in line with the restoration of balanced oxidative status as indicated by the increased total antioxidant capacity, glutathione and superoxide dismutase activity, and the decreased malondialdehyde content in testes (p < 0.05 vs. cisplatin). TRN increased the cell proliferation revealed by the increased expression of proliferating cell nuclear antigen in a dose-dependent manner (p < 0.05 vs. cisplatin) whereas only TRN300 decreased testicular cJNK, TRAIL, and caspase-8 expression (p < 0.05 vs. cisplatin). Moreover, TRN dose-dependently inhibited the pro-inflammatory transcription factor NF-kB and the cytokine TNF-α expressions in testes. In conclusion, TRN300 was more effective than TRN100 in alleviating cisplatin-induced testicular and epididymal injuries and in enhancing spermatogenesis. This curative effect of TRN might be mediated through its antioxidant and anti-inflammatory impacts along with its modulatory impact on cJNK/TRAIL/caspase-8 signaling favoring proliferation rather than apoptosis.

Clavo en un testículo / Nail in a testicle

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