Is testicular tissue resection effective in testicular compartment syndrome?

Background: There have been many testicular losses due to testicular compartment syndrome (TCS). Studies are ongoing to lower the pressure within tunica vaginalis during TCS. Aims: To provide enough space for reperfusion of the testicular tissue and to reduce intratesticular pressure by resecting testicular tissue in the affected testis for treatment of TCS. Materials and Methods: The study was designed as a prospective randomized animal study. A total of 24 Wistar albino adult rats were randomly divided into three groups. After torsion surgery group 1 underwent detorsion + testicular tissue resection (TTR), while only detorsion was performed in group 2. The control group did not undergo any procedures. At the postoperative 5th day all subjects were sacrificed, and their testes were evaluated in terms of histologic findings, apoptosis, and microangiogenesis. One-way ANOVA and Tukey's test were used for analysis. Results: According to Johnsen scores, all the groups were statistically different from each other and the damage in group 1 was less than in group 2 (P < 0.05). Factor VIII expressions in surgical groups were significantly higher than in the control group (P < 0.05). However, the surgical groups did not show any significant difference between each other (P > 0.05). Apoptotic cell counts were higher in both surgical groups than in the control group. Also, there was significantly higher apoptotic cell count in group 2 than in group 1 (P < 0.05). Conclusions: The injury secondary to TCS is lower when TTR is performed. In the cases in which tunica vaginalis graft could not be obtained or in the delayed cases, TTR may be useful.

[Non-infectious emergencies of the lower urinary tract and genitals]. / Urgences non infectieuses du bas appareil urinaire et des organes génitaux.

INTRODUCTION: The objective of this narrative review was to report the most relevant data on the contemporary management of the main non-infectious emergencies of the lower urinary tract and genital organs. METHODS: A narrative synthesis of the articles (French, English) available on the Pubmed database was carried out in June 2021. A request to the health surveillance network for emergencies and deaths (SurSaUD®, Santé Publique France) revealed original data on the epidemiology of non-infectious lower urinary tract and genital organs emergencies. RESULTS: Non-infectious emergencies of the low urinary tract and genital organs represent a large panel of traumatic and non-traumatic situations, which constitute the 3rd reasons in urology for a consultation at the emergency department after, infectious disease (1st) and non-traumatic/non-infectious emergencies of the upper urinary tract (2nd). Hematuria is the 3rd urological reason for men for a consultation at the emergency department. Globally, pelvic trauma and genital traumatism mainly concern men. These emergencies rarely affect the prognosis but can be integrated into more complete situations which are likely to impact their treatment, particularly in multiple traumas. CONCLUSIONS: In this article we report the epidemiology and the principles of management of non-infectious emergencies of the lower urinary tract and genital organs.

Investigation of the protective effect of nesfatin-1 on testicular ischaemia-reperfusion damage: An experimental study.

This study aimed to determine oxidative stress in the tissue after testicular torsion biochemically and histopathologically and to examine the effects of Nesfatin-1 treatment on this injury. Thirty-two rats were randomly divided into four groups: sham, torsion + detorsion (4 hr torsion followed by 1 hr detorsion), ischaemia/reperfusion + saline (I/R + S) and I/R + nesfatin-1. I/R + S group a single-dose saline treatment was administered intraperitoneally at the two-hundred-tenth minute of torsion (ischaemia; 10 cc/kg). Similarly, I/R + nesfatin-1 group a single dose of nesfatin-1 treatment was administered intraperitoneally at the two-hundred-tenth minute of ischaemia (10 µg/kg). Myeloperoxidase, total oxidant status and oxidative stress index values were significantly increased in the I/R and I/R + S group compared to the sham group. Superoxide dismutase was significantly decreased in the I/R + S group compared to the sham group. No significant difference was found between the I/R + nesfatin-1 group and the other I/R groups (I/R and I/R + S) in terms of biochemical parameters. The mean diameter of the seminiferous tubule decreased in the I/R groups. However, the mean diameter of the seminiferous tubules was not significantly different between the I/R + S group and the I/R + nesfatin-1 group. Thus, the administration of nesfatin-1 after ischaemia did not reduce testicular-oxidative stress.

The ultrasonographic "whirlpool sign" in testicular torsion: valuable tool or waste of valuable time? A systematic review and meta-analysis.

PURPOSE: A positive whirlpool sign (WS) is defined as the presence of a spiral-like pattern when the spermatic cord is assessed during ultrasonography (US), using standard, high-resolution ultrasonography (HRUS) and/or color Doppler sonography (CDS), in the presence of testicular torsion. The objective of this review was to assess the validity and accuracy of this sign by performing a comprehensive systematic literature review and meta-analysis. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a comprehensive literature search was performed (August, 2017), using the following databases: BMJ Best Practice, Cochrane Library, Embase, PubMed, Scopus, and Web of Science. Selected studies were further assessed for relevance and quality using the Oxford 2010 Critical Appraisal Skills Program (CASP). RESULTS: Of the studies assessed, a total of 723 participants were included, with a mean of 72.3 (SD 71.9) participants. Of the participants, 226 (31.3%) were diagnosed with testicular torsion (TT). Meta-analysis of the studies that provided sufficient data resulted in a pooled sensitivity and specificity of the WS of 0.73 (95% CI, 0.65-0.79) and 0.99 (95% CI, 0.92-0.99), respectively. Removal of all neonates increased the pooled sensitivity to 0.92 (95% CI, 0.70-0.98) while the pooled specificity remained almost unchanged at 0.99 (95% CI, 0.95-1.00). The estimated summary effect of all studies with sufficient data was 4.34 (95% CI, 1.01-7.67; n = 394; p = 0.001). A large degree of heterogeneity was suggested by an I2 statistic of 88.27% (95% CI, 68.60-98.68%). Removal of neonatal subjects increased the estimated summary effect to 5.32 (95% CI, 1.59-9.05; n = 375; p = 0.001). CONCLUSION: The WS, when correctly diagnosed, may be viewed as a very definitive sign for TT in the pediatric and adult populations. However, its role in neonates is limited.

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

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

The efficiency of Poly(ADP-Ribose) Polymerase (PARP) cleavage on detection of apoptosis in an experimental model of testicular torsion.

The aim of this study was to evaluate the histopathological and apoptotic changes occurring in the rat ipsilateral and contralateral testes, after experimental spermatic cord torsion, and to explore and the role of poly(ADP-ribose) polymerase (PARP) cleavage in testicular torsion-detorsion injury. A total of 37 Wistar albino rats were subjected to 720° unilateral spermatic cord torsion for 1, 2 and 4 h, followed by 4-h reperfusion, or else to a sham operation (control group). Histology of the testicle was evaluated using haematoxylin-eosin (H&E) staining and Johnsen's scoring system. Germ cell apoptosis was evaluated via active caspase-3 immunostaining, and PARP expression levels were evaluated via Western blotting. The mean Johnsen's tubular biopsy scores (JTBS) of the ipsilateral testicles were lower for all torsion groups than for the controls (P < 0.05), but the JTBS of the contralateral testicles were only lower in the 4-h torsion group (P < 0.05). The mean apoptosis score (AS) of the ipsilateral and contralateral testicles was significantly higher in the torsion groups than in the sham group. AS increased correlatively with torsion time, in both testicles. The effect of testicular torsion on PARP cleavage was time dependent, with the highest effect observed after 4 h of testicular torsion (P < 0.05). Testicular torsion caused time-dependent histological changes, apoptosis and increases in PARP cleavage. Our results suggest that testicular torsion-detorsion injury caused cell damage and germ cell apoptosis that apparently involved cleavage of PARP. Increased PARP cleavage could, in turn, lead to enhanced apoptosis.

Determination of M1/M2 Macrophage Polarization in Ipsilateral and Contralateral Rat Testis Tissue Following Unilateral Torsion/Detorsion.

The present study investigates the changes in M1/M2 macrophage polarization resulting from unilateral testicular torsion in the bilateral testis. The study sample included 63 male Sprague-Dawley rats, which were randomly divided into nine groups (n = 7): Control, Sham (4 h (4 h), 24 h, 7 days (7d), 14d), and Torsion/Detorsion (T/D) (4 h, 24 h, 7d, 14d). Histopathological evaluations revealed no changes in the Sham groups, while T/D was noted to cause edema, vascular occlusion, disruption of seminiferous tubule epithelial organization, germ cell abnormalities and structural anomalies in the experimental rats, the severity and extent of which increased from 4 h to 14d after T/D. The Cosentino scores used to determine the degree of histological damage were consistent with the histopathological findings in all groups, while the Johnsen scores, as a marker of spermatogenesis, were lower in the T/D groups. Seminiferous tubule diameters and germinal epithelial thickness decreased significantly in parallel with increased tubule damage in the ipsilateral testicles. Testicular torsion significantly affected sperm motility, with significant reductions observed in the T/D 7d and T/D 14d groups. A hormone profile analysis revealed decreased testosterone levels in both the Sham and T/D groups when compared to the Controls. CD68 and CD163 immunoreactivities, as M1 and M2 macrophage surface markers, were determined in the testicular tissue using the avidin-biotin-peroxidase complex method. T/D interventions caused M1/M2 macrophage polarization changes and increased M1 macrophages, particularly in contralateral testicular tissue. The increase in M1 macrophages in contralateral testicular tissue following T/D in the present study suggests that cell processes, including macrophages, may play an important role in contralateral testicular injury.

Protective effect of Smilax excelsa L. pretreatment via antioxidant, anti-inflammatory effects, and activation of Nrf-2/HO-1 pathway in testicular torsion model.

The protective effects of the ethanol extract of Smilax excelsa L. (SE) leaves were investigated on testicular tissue of rats with a torsion model in this study. The chemical composition of the extract was detected by means of liquid chromatography with tandem mass spectrometry (LC-MS/MS). SE extract was given for 21 days before torsion was created in the treatment group. The sperm parameters of the torsion group were impaired, and there was an increase in MDA level as well as a decrease in GSH level and GPx activity compared to the control group. TNF-α and NF-κB levels in the torsion group increased as compared to those in the control group. The expression levels of Nrf-2 and HO-1 were lower in the torsion group than those in the control group. The SE pretreatment group has improved sperm, oxidative stress, and inflammatory markers when compared to the torsion group, and the Nrf-2/HO-1 pathway was activated. PRACTICAL APPLICATIONS: Smilax excelsa L. is a plant with economic value used in traditional medicine in the treatment of stomachache, bloating, and breast cancer in Northwest Anatolia. It has an antioxidant effect due to the flavonoids and anthocyanins it contains. The protective effect against ischemia-reperfusion-induced tissue and reproductive damage in testicular tissue were demonstrated with the study. When the histological examinations of the tissues were evaluated, it was found that morphological structure of the tissues was retained in the treatment group. The findings indicate that SE prevents tissue damage in the torsion model by antioxidant and anti-inflammatory effects and activating Nrf-2/HO-1 pathway.

Recurrent testicular torsion post orchidopexy - an occult emergency: a systematic review.

BACKGROUND: Recurrent Testicular Torsion (RTT) is a rarely reported event after previous testicular torsion (TT) repair. Both conditions have similar signs and symptoms. Various techniques have been attempted to reduce the incidence of retorsion. This review assesses the presentation, diagnosis, risk factors, management and outcomes associated with RTT. METHODS: After PROSPERO Registration (CRD42021258997), a systematic search of PubMed, Google Scholar, Embase, Scopus, Web of Science, Cochrane Database of Systematic Reviews, Global Index Medicus and Cumulative Index to Nursing and Allied Health Literature (CIANHL) was performed using specific search terms. Study metadata including patient demographics, orchidopexy techniques, RTT rates and RTT timing were extracted. RESULTS: Twenty-six articles, comprising 12 case series and 14 case reports, with a total of 46 patients were included. Overall, the median (IQR) age of the pooled cohort was 18 (15-26) years, the median (IQR) time to presentation was 6 (3-36) hours from the onset of testicular pain. The most common presenting features were testicular pain (100%), testicular swelling (60.9%) and a high riding testicle (34.8%). The left testicle was most commonly affected (63.0%), RTT was on the ipsilateral side in relation to the primary episode of TT in 52.2% of cases, the median (IQR) interval between torsion and retorsion events was 4 (1.3-10.0) years, non-absorbable sutures were the most common suture material used during orchidopexy after RTT (88.9%). CONCLUSION: RTT is a rare presentation to the Emergency Department. Even with a prior history of TT, RTT should be considered in patients presenting with classic symptoms.

The long term effects of intrascrotal low dose and high dose N-acetylcysteine on testis damage in rat model of testicular torsion.

BACKGROUND/PURPOSE: During testicular torsion, the testes face oxidative damage owing to ischemia/reperfusion. We studied the long term effects of the intrascrotal administration of N-acetylcysteine (NAC) during detorsion procedure in a rat model of testicular torsion. METHODS: Twenty-eight rats were divided into 4 groups: (1) Control group: No procedure was done (2): Torsion-detorsion group: Testis torsion applied for 3 h (3): Low Dose Group: After testis torsion-detorsion (for 3 h) 10 mg/kg NAC was given into tunica vaginalis (4): High Dose Group: After testis torsion-detorsion (for 3 h) 100 mg/kg NAC was given into tunica vaginalis. We measured dimensions of the testes and examined pathological findings and Johnsen and Cosantino Scores. RESULTS: For testes height and volume, high dose NAC group had better results than the torsion-detorsion group (p = 0.019, p = 0.049). Testes weight showed no difference (p = 0.204). Sertoli cell number per tubule in the high dose NAC group was statistically different than the torsion-detorsion group (p = 0.017). CONCLUSIONS: When NAC was given intrascrotally at a dose of 100 mg/kg, it decreased the loss of testis volume and height, and Sertoli cell number per tubule was similar to the control group. These results suggest that the higher dose intrascrotal NAC administered during detorsion may have a protective effect.

Testicular Torsion in the Emergency Room: A Review of Detection and Management Strategies.

Testicular torsion is a challenging and time-sensitive diagnosis that is encountered frequently in daily practice, especially in the emergency room. A thorough history, the presence of a painful and swollen testis and testicular ultrasonography plays a vital role in the prompt diagnosis of testicular torsion. Prompt diagnosis is essential to prevent complications of testicular torsion which include testicular infarction, necrosis, and sub/infertility. This can be challenging as there are various other conditions that may mimic the presentation of testicular torsion. Since testicular torsion is an extremely time-sensitive diagnosis, it may also be a subject of many medicolegal challenges. This review article serves as a guide for clinicians involved with the diagnosis and management of testicular torsion. We review and discuss detection and management strategies based on their validity, statistical significance, and effectiveness in enabling prompt diagnosis and management of testicular torsion. Medicolegal implications of testicular torsion are also highlighted.

Near-infrared spectroscopy in the diagnosis of testicular torsion: valuable modality or waste of valuable time? A systematic review.

BACKGROUND: Testicular torsion (TT) is a urological emergency that affects one in 4000 males younger than 25 years. Delays in the management of TT may result in testicular ischaemia, testicular necrosis, orchidectomy and infertility. This review assesses the validity of near-infrared spectroscopy (NIRS) as a diagnostic tool in the assessment and diagnosis of TT. METHODS: A systematic search of Cochrane Database of Systematic Reviews, EMBASE, Google Scholar, PubMed, Scopus and Web of Science databases was performed in January 2019 using specific search terms. Selected studies were ranked and evaluated using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: A total of nine studies that included 253 subjects (88 animals and 165 humans) with a mean sample size of 28.1 (standard deviation 40.8) subjects were included. The mean difference in testicular tissue oxygen saturation between torsed and non-torsed testes (Δ%StO2 ) were 45%, 42% (±5%), 26% and 5-18% in four animal studies and 2.0%, 3.0%, 6.7%, 6.8% and 23.0% in five human studies. The tissue oxygen saturation difference between contralateral healthy testes (controls) ranged from 1% to 10% in the five studies that alluded to this. CONCLUSION: The current body of evidence does not support the use of NIRS in the work-up of TT. Well-designed clinical trials with large patient samples are required to determine whether NIRS may have some future role as a diagnostic modality in TT.

Predictive value of hematological parameters in testicular torsion: retrospective investigation of data from a high-volume tertiary care center.

OBJECTIVE: To investigate the use of hematological parameters in the differential diagnosis of testis torsion and epididymo-orchitis, and to determine the predictive value of these parameters in the diagnosis of testis torsion. METHODS: This study retrospectively reviewed the medical data of patients who presented to our institute with the complaint of acute scrotal pain. Eighty-five patients who had undergone orchiectomy or surgical detorsion due to testis torsion and 72 patients with epididymo-orchitis were included in the study. The control group comprised 78 healthy males. The groups were compared with respect to age, hematological parameters, neutrophil to lymphocyte ratio (NLR), monocyte to eosinophil ratio (MER), and platelet to lymphocyte ratio (PLR). RESULTS: The monocyte count significantly differed between testis torsion and epididymo-orchitis, and was useful in the differential diagnosis. The mean neutrophil, platelet, and white blood cell counts, and the NLR, MER, and PLR values in the control group were significantly lower than those in the torsion and epididymo-orchitis groups. CONCLUSION: The sensitivity and specificity of NLR in predicting testis torsion were as high as the sensitivity and specificity of doppler ultrasonography, suggesting the possible use of this parameter in the diagnosis of testis torsion.

Nesfatin-1 ameliorates testicular injury and supports gonadal function in rats induced with testis torsion.

Testicular torsion causes ischemia-reperfusion injury and an increased risk of infertility. Nesfatin-1 is a novel peptide with antioxidant, anti-inflammatory and anti-apoptotic properties. In the present study, we aimed to investigate the putative beneficial effects of nesfatin-1 on oxidative injury and impaired testicular function induced by testis torsion. Under anesthesia, male Sprague-Dawley rats (180-230 g; n = 24) had sham-operation or they underwent testicular torsion by rotating the left testis 720° and fixing it for 2 h, followed by a 2-h detorsion. Rats in each group were treated intraperitoneally with either nesfatin-1 (0.3 µg/kg) or saline prior to the torsion or sham-torsion. At the end of the 4-h experimental period, tissue samples were removed for evaluation of spermatozoa, molecular and histochemical analyses. In saline-treated torsion/detorsion group, a high percentage of abnormal spermatozoa with head defects was observed, which was abolished in nesfatin-1-treated torsion/detorsion group. The levels of 8-OHdG, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, caspase-3 were increased in the saline-treated torsion/detorsion group as compared to sham-operated group, while nesfatin-1 pre-treatment significantly decreased the expressions of the pro-inflammatory cytokines, depressed apoptosis, and also reduced the tubular degeneration. In addition, nesfatin-1 in torsion/detorsion group elevated expressions of transforming growth factor (TGF)-beta and reduced expressions of protein kinase B (AKT) and cAMP response element binding protein (CREB) in the testis tissue. The present findings show that nesfatin-1, by regulating AKT and CREB signaling pathways and pro-inflammatory/anti-inflammatory cytokine balance, preserves the spermatogenic cells and ameliorates torsion-detorsion-induced tubular degeneration.

Testicular torsion in undescended testis: A persistent challenge.

OBJECTIVE: To evaluate the management and outcomes of patients who presented with torsion of an undescended testis and review the reported series in the literature. METHODS: The case records of 13 patients operated for testicular torsion involving undescended testis were retrospectively reviewed. The medical records included age at presentation, medical history, physical examination, operative findings and the results of follow-up. The diagnosis of torsion of undescended testis was made clinically and confirmed by inguinal exploration. RESULTS: In six cases the testis was preserved and orchiopexy was performed, while in seven cases orchidectomy was performed due to testicular gangrene in six patients and testicular tumor discovered peroperatively in one case. Mean duration of symptoms at time of surgery in the orchiopexy group was 6.5 h and in the orchidectomy group was 21.2 h. From six patients treated by orchiopexy, two patients suffered from testicular atrophy at a mean of 24 months. CONCLUSION: Testicular torsion in undescended testis is still diagnosed with delay which may affect testicular salvage. The importance of examination of external genital organs is highlighted which should be routinely included by emergency physicians in physical examination for abdominal or groin pain.

The role of CAPE in PI3K/AKT/mTOR activation and oxidative stress on testis torsion.

Ischemia reperfusion injury arises from testicular torsion resulting in a loss of spermatogenesis and significant germ cell apoptosis. This study evaluates the prooxidant/antioxidant effects of caffeic acid phenethyl ester (CAPE) through PI3K/AKT/mTOR signal pathways on testis torsion. A total of (28) male Wistar rats were divided randomly into 4 groups (n=7 for each group):group A (sham) group,group B torsion/detorsion group, group C (saturation group, during four days of CAPE, one dose (10 µmol/kg, i.p)) and group D (a single dose of CAPE 2h after torsion and before detorsion). At the end of the study, unilateral orchiectomies were performed for measurements of MDA and 8OHdG levels, histopathologic and immunohistochemical and TUNEL apoptotic cell examination. Testicular torsion-detorsion led to a significant decrease in the mean values of the Johnsen's scores and a significant increase in the apoptotic cell values of group B. There were no significant differences between group D and group A. In addition, the MDA and 8OHdG levels increased significantly in group B. The MDA and 8OHdG values were lower in group D. However, the 8OHdG levels were higher in group C than the groups A and D. On the other hand, CAPE suppresses mTOR activation and reduces the apoptosis on ischemia/reperfusion damage in rat testis. These results demonstrate that CAPE suppresses mTOR activation and reduces the apoptosis on ischemia/reperfusion damage in rat testis.

The protective effect of goji berry extract in ischemic reperfusion in testis torsion.

This study investigated whether goji berry extract (GBE), a known antioxidant, reduces ischemic reperfusion injury when administered to rats exposed to experimental testis torsion. A total of 32 Sprague-Dawley male rats were randomized into 4 groups, including the control (sham), goji, torsion, and torsion-goji groups. The treatment groups received intraperitoneal GBE prior to torsion. The left testes of the animals were subjected to torsion via 5 hours of ischemia and 6 hours of reperfusion. TAC (total antioxidant capacity), TOS (total oxidant status) and OSI (oxidative stress index) levels were calculated. Approximately 5-µm-thick sections were stained with hematoxylin-eosin (H&E) and examined under a light microscope. Statistical analyses were performed with the SPSS 15 software package. The mean serum TAC level was significantly increased in Groups 2 and 4 compared with Groups 1 and 3 in biochemical analyses (for both P < 0.001). The mean serum TOS level was significantly increased in Group 3 compared with Groups 1, 2, and 4 (P < 0.001, P < 0.001, and P = 0.003, respectively). Comparison of the groups with regard to histopathological examination revealed that Group 4 exhibited a significantly higher rate of hemorrhage and congestion compared with Groups 1 and 2 (P = 0.038). The groups did not differ significantly with respect to degeneration. Ischemic reperfusion injury associated with testis torsion was reduced by the antioxidant effect of GBE. Further experimental and clinical studies are needed to confirm the agent's efficacy for this indication.