Protective effect of liraglutide on experimental testicular ischaemia reperfusion in rats

This study was performed to evaluate the effect of liraglutide on experimental testicular ischaemia reperfusion in rats in terms of biochemistry, histopathology and immunohistochemistry. A total of 28 male Wistar-Albino rats were divided randomly into 4 groups: control (7), sham (7), ischaemia-reperfusion (7) and ischaemia-reperfusion + liraglutide (7). Biochemically, Nitric Oxide, Malondialdehyde, Superoxide dismutase, Glutathione peroxidase and Catalase levels were measured in the testis. Apoptosis protease activating factor-1 and inducible nitric oxide synthase activity were evaluated immunohistochemically as well. Statistical analyses were made via the Kruskal–Wallis and Mann–Whitney U tests. In the reperfusion group, CAT and SOD values were increased (p > .05), NO and MDA values were decreased (p < .05) after administration of liraglutide. In addition, GPx values were significantly increased in ischaemia reperfusion + liraglutide administered group compared to reperfusion group (p < .05). Apaf-1 and iNOS activity were significantly decreased with the addition of liraglutide treatment to the ischaemia-reperfusion group (p < .05). First of all, we would like to say that liraglutide treatment is moderately preventive against I/R injury in testicular torsion. The anti-inflammatory, antioxidant and antiapoptotic properties of liraglutide are create a moderately protective effect as we show in this study.     

Protective effects of thymoquinone on experimental testicular ischaemia–reperfusion injury: an apoptotic,proliferative and biochemical study

The objective of this study was to examine the effects of thymoquinone (TQ), which has antioxidant properties in the experimental testicular I/R model in rats in terms of its anti‐apoptotic, proliferative and biochemical attributes. In our study, 24 male rats were divided into three groups: control group, I/R group and I/R+TQ group. Testicular torsion was created by rotating the left testis 720° in a clockwise direction. The ischaemia period was 4 h, and an orchiectomy was performed after 4 h of detorsion. Spermatogenesis and the mean seminiferous tubule diameter were significantly decreased in the I/R groups compared to the control group. Furthermore, TQ‐treated animals displayed an improved histological appearance in the I/R group. It was also observed that treatment with TQ increased the activity of PCNA, which decreased as a result of I/R, and this treatment also reduced the number of TUNEL‐positive cells. The I/R+TQ group showed a decrease in malondialdehyde levels and an increase in the activities of superoxide dismutase, catalase and glutathione peroxidase in comparison with the I/R group. It could be concluded that cytoprotective effects of TQ on the I/R testicles are via reduction of apoptosis, oxidative stress and lipid peroxidation.     

Effects of co-administration of dopamine and vitamin C on ischaemia-reperfusion injury after experimental testicular torsion-detorsion in rats

The objective of this study was to investigate the effects of dopamine as vasodilator, vitamin C as an antioxidant and combined administration of them on ischaemia-reperfusion (I-R) injury following testicular torsion (TT). Thirty adult male rats were divided into six groups each containing five rats. Testicular ischaemia was achieved by twisting the left testis for 4 h. Group 1 was for determination of the basal values. Group 2 had 4 h TT. Group 3 had 4 h TT and was then treated with dopamine. Group 4 had 4 h TT and was then treated with vitamin C. Group 5 had 4 h TT and was then treated with dopamine and vitamin C. Group 6 was designed as a sham operated group. Testicular torsion caused a significant decrease in the percentage of spermatogenesis and seminiferous tubules diameters compared with the control and sham groups. Administration of dopamine, vitamin C and their combination increased above mentioned parameters and decreased serum malondialehyde levels significantly. However, vitamin C had better results than the other treatments (P < 0.05). In conclusion, a potent antioxidant like vitamin C was found to be more effective than increasing blood flow by a vasodilator like dopamine on improving I-R injury following TT.     

Protective effects of Urtica dioica L. on experimental testicular ischaemia reperfusion injury in rats

In this study, it was aimed to examine the effects of Urtica dioica L. (UD) that has antioxidant feature in the experimental testicular I/R model in rats in terms of anti‐apoptotic and antioxidative effects. In our study, 24 male rats were divided into three groups: control group, I/R group and I/R + UD (2 mg kg^?1) group. Seminiferous tubule calibre measurement, Johnson score, haematoxylin–eosin staining, proliferative cell nucleus antigen (PCNA) immunohistochemical staining and TUNEL as histopathological have been conducted. The structural deterioration in the testicular on I/R group has reduced after the treatment of UD. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end labelling (TUNEL), and there was a rise in the expression of proliferating cell nuclear antigen (PCNA) in testis tissues of UD‐treated rats in the I/R group. The I/R + UD group showed a decrease in malondialdehyde levels and an increase in the activities of superoxide dismutase, catalase and glutathione peroxidase in comparison with the I/R group. It could be concluded that protective effects of UD on the I/R testicles are via reduction of histological damage, apoptosis, oxidative stress and lipid peroxidation.     

The protective effect of darbepoetin alfa on experimental testicular torsion and detorsion injury

AIM: Testicular torsion is a serious urological emergency, usually involving newborns, children, and adolescents which can lead to subfertility and infertility. Prevention of testicular damage caused by torsion is still a clinical and experimental problem. So far many chemicals and drugs have been investigated for decreasing ischemia/reperfusion (I/R) injury in experimental animals. The possible protective effect of darbepoetin alfa, a novel erythropoietic protein, on testicular tissue after I/R injury was examined in this study. METHODS: Thirty rats were divided into three groups: sham operation, torsion/detorsion, and torsion/detorsion plus darbepoetin alfa groups. After torsion (2 hours) and detorsion (4 hours), bilateral orchiectomy was performed. Malondialdehyde, nitric oxide and glutathione levels were determined in testicular tissue. RESULTS: Administration of darbepoetin alfa caused a decrease of malondialdehyde and nitric oxide levels and an increase in glutathione levels compared with the torsion/detorsion group. In addition, histological injury scores were significantly decreased in the treatment group more than the torsion/detorsion group. CONCLUSION: The results suggest that darbepoetin alfa may be a potential protective agent for preventing testicular injury caused by testis torsion.     

The protective effect of cinnamon and ginger hydro-alcoholic extract on carbon tetrachloride-induced testicular damage in rats

Sexual dysfunction of men is one of the most serious problems in human society. This study aimed to evaluate the protective effect of cinnamon and ginger extract on testicular damages induced by carbon tetrachloride (CCl4). Thirty-six male Wistar rats were randomly divided into 6 groups (n = 6): 1. Normal control; 2. Carbon tetrachloride (CCl4); 3. CCl4 + Cinnamon; 4. CCl4 + Ginger; 5. CCl4 + Cinnamon and Ginger; and 6. Cinnamon + Ginger. CCl4 (1 ml/kg) was injected intraperitoneally on the 14th day, and cinnamon (50 mg/kg, orally) and ginger (250 mg/kg, orally) were administered daily for 14 days. Fifty hours after the CCl4 injection, the testicles and epididymis were separated and examined as to histological alterations and oxidative stress markers. CCl4 significantly increased malondialdehyde level and decreased total antioxidant capacity when compared to the normal control group (p < .05). In addition, degenerative alterations in the testicular and epididymal tissue were observed in CCl4 group. The pre-treatment with ginger and cinnamon extract significantly improved these parameters when compared to the CCl4 group (p < .05). The results of this study indicated that co-treatment of ginger and cinnamon reduces the damages induced by CCl4 in testicular tissue by increasing antioxidant capacity and reducing lipid peroxidation.     

Quercetin has a protective role on histopathological findings on testicular ischaemia-reperfusion injury in rats

We investigated the effects of quercetin on pathological findings on testicular ischaemia-reperfusion (I/R) injury in rats. Twenty-four male Wistar albino rats were randomly assigned into four groups: Group 1, control (n = 5); Group 2, sham (n = 4); Group 3, I/R (n = 8); and Group 4, I/R + quercetin (n = 7). Bilateral testicular artery and vein were occluded for 1 h, followed by reperfusion in I/R and I/R + quercetin animals. Quercetin (20 mg kg(-1) per day) was administrated once daily by gavage to Group 1 and Group 4, respectively, after reperfusion. At the end of the study, bilateral orchiectomies were performed for histopathologic examination. The tissue damage was evaluated with light microscopy. Normal inter-stitium and seminiferous tubules were observed in control group. In the sham group, rats were seen minimal oedema around the seminiferous tubules and congested vascular structures. In Group 3, oedema, vascular congestion and haemorrhage between seminiferous tubules were observed. In Group 4, histopathologic features were markedly less than Group 3 (P = 0.03). Our study demonstrated that quercetin seems to have a protective effect on testis histopathology in rats with testicular I/R.     

实验性睾丸缺血超声表现与别嘌醇药物保护作用的相关性研究

目的:探讨不同程度急性单侧睾丸缺血及再灌注后的灰阶、彩色多普勒及超声造影表现与别嘌醇药物保护疗效的相关性。方法:42只新西兰大白兔随机分成对照组、缺血组(A、B、C组)和缺血给药组(D、E、F组),每组6只。缺血组与缺血给药组在超声监测下制成不同程度的单侧睾丸缺血模型,A组与D组,睾丸回声均匀、血流信号轻度减少;B组与E组,睾丸回声不均匀、血流信号明显减少;C组与F组,睾丸出现放射状或小片状低回声、血流信号消失。A、B、C组分别出现上述声像图变化后直接予以再灌注。缺血给药组出现上述声像图变化后腹腔注射别嘌醇(200 mg/kg)后予以再灌注。各组再灌注前及再灌注后3 d分别行双侧睾丸超声造影。再灌注3 d后观察各组术侧睾丸的病理变化与丙二醛(m alond ialdehyde,MDA)含量改变。比对分析不同程度急性单侧睾丸缺血超声表现与别嘌醇治疗疗效之间的关系。结果:睾丸超声造影表现,对照组呈"快进快退";再灌注前,A组与B组呈"慢进慢退,"C组呈大面积中央型"充盈缺损",再灌注后3 d,各缺血组呈"快进慢退",以C组最明显;D、E、F组超声造影表现均分别与A、B、C组相同。D组[(9.10±0.23)分]与A组[(8.53±0.22)分]比较,E组[(7.03±0.20)分]与B组[(5.82±0.33)分]比较,Johnsen's评分均有明显提高(P<0.05),F组[(2.45±0.33)分]与C组[(2.30±0.53)分]比较,Johnsen's评分无明显提高(P>0.05);D组[(1.68±0.43)%]与A组[(7.12±0.84)%]比较,E组[(12.53±0.59)%]与B组[(20.87±1.59)%]比较,凋亡指数均有明显降低(P<0.05),F组[(51.23±2.53)%]与C组[(52.93±2.62)%]比较,凋亡指数无明显降低(P>0.05)。D组[(0.64±0.05)nmol/mg prot]、E组[(1.59±0.06)nmol/mg prot]、F组[(3.10±0.17)nmol/mg prot]分别与A组[(1.38±0.07)nmol/mg prot]、B组[(2.11±0.08)nmol/mg prot]、C组[(3.25±0.14)nmol/mg prot]比较,缺血侧睾丸MDA含量均有明显降低(P<0.05)。结论:睾丸表现为轻度或中度缺血时,别嘌醇对睾丸生精功能的恢复有帮助,当表现为重度缺血时,别嘌醇对睾丸生精功能的恢复无明显效果。超声技术尤其是超声造影有助于指导睾丸缺血的药物治疗及预测疗效。     

Protective effects of Stevia rebaudiana aqueous extract on experimental unilateral testicular ischaemia/reperfusion injury in rats

This project aimed to examine Stevia rebaudiana aqueous extract protective effects on testicular ischaemia/reperfusion injury of rats. Forty rats were randomly divided into five groups: (1) sham group, (2) torsion/detorsion group, (3 and 4) low and high doses treatment groups received S. rebaudiana extract intraperitoneally 30 min before detorsion by 500 and 1,000 mg/kg respectively, and (5) healthy group received the extract by 1,000 mg/kg. In this study, left testes were rotated 2 hr, reperfusion period took long 5 hr, and then orchiectomy was performed. Histopathological and biochemical evaluations of testicular tissue samples were performed. Histopathologically, sham and healthy groups exhibited normal seminiferous tubules. Germinal cell necrosis, interstitial oedema, haemorrhage and congestion were seen in torsion/detorsion group. Testicular tissues of both treatment groups revealed lower histopathological alterations. Significant higher malondialdehyde level was observed in torsion/detorsion group than sham and healthy groups (p < .05). Compared with torsion/detorsion group, S. rebaudiana extract significantly reduced malondialdehyde level in treatment groups (p < .05). Torsion/detorsion group had significantly lower glutathione peroxidase and superoxide dismutase activities than sham and healthy groups, and these parameters showed significant increase in treatment groups compared with torsion/detorsion group (p < .05). The results revealed S. rebaudiana has this potential to protect the testes from ischaemia/reperfusion injury.     

The protective effect of Kombucha against silver nanoparticles-induced toxicity on testicular tissue in NMRI mice

Silver nanoparticles (SNPs) can pass from the cell membrane and testicular blood barrier due to their small size, and by increasing oxidative stress they cause disorder in the male reproductive system. Kombucha is a traditional fermented drink with detoxification and potent antioxidant properties. We aimed to examine the protective effect of Kombucha against the damages due to SNPs on the testis tissue. In this experimental study, NMRI mice were randomly separated into four groups (n = 6), namely control (distilled water), SNPs (500 mg/kg), Kombucha extract (9 ml/kg) and SNPs + Kombucha, and were treated with gavage for 35 days. A significant decrease in testosterone level and total antioxidant capacity, and a significant increase in malondialdehyde concentration was observed in the SNPs group in comparison with the control group. Histological studies on the testis of mice treated with SNPs showed vacuolation, decrease in generational epithelium thickness, seminiferous tubules diameter, testis volume and the number of spermatozoa in lumen of the seminiferous tubule and increase in the volume of interstitial space while the mentioned parameters were improved in the SNPs + Kombucha group compared to the SNPs group. Kombucha reduces the adverse effects of SNPs on testis tissue and improves the function of the male reproductive system.     

Protective effect of ebselen on experimental testicular torsion and detorsion injury

Ebselen is used as a drug in clinical trials against stroke, reperfusion injury with anti‐atherosclerotic and renoprotective effects. The aim of this study is to investigate the protective effect of ebselen, on torsion/detorsion (T/D)‐induced biochemical and histopathological changes in experimental testicular ischaemia/reperfusion injury. A total of 28 male Wistar Albino rats were divided into four groups: group 1(sham‐operated group, n = 7), group 2(ebselen group, n = 7), group 3(torsion/detorsion + saline, n = 7) and group 4(T/D + 10 mg kg^?1 ebselen group, n = 7). The tissue homogenate samples were used for immediate nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase, catalase and glutathione measurement. Testes in all groups were evaluated for the biochemical assay and histopathological examinations. To evaluate spermatogenesis, Johnsen scoring system was used. Testicular tissue MDA and NO levels in group 3 were significantly higher than in group 1 and 4. In histological evaluation of the testicular tissues, ebselen administration improved tubular histology significantly compared with T/D group. Significant increase in histological score was observed in the testis of group 3 compared with group 1 and 2. Histological score in group 4 significantly decreased compared with group 3. Johnson score was significantly lower in T/D group compared with all other three groups, ebselen administration increased the score significantly compared with T/D group. Ebselen reduced oxidative biochemical and histopathological damage in our testicular T/D rat model.     

Protective effect of thymoquinone against testicular torsion induced oxidative injury

We aimed to determine the protective effects of thymoquinone (TQ), against ischaemia–reperfusion (I/R) injury in the testis tissue of rats. Twenty‐seven male Wistar albino rats were randomly divided into three equal groups as follows: Group I, sham group; Group II, torsion group; and Group III, torsion + thymoquinone group. The ischaemia period was 2 h, and orchiectomy was performed after 30 min of detorsion. Testis tissue sections were analysed with the terminal transferase mediated dUTP‐nick end labelling (TUNEL) assay to determine in situ apoptotic DNA fragmentation. Additionally, Caspase 3 and Bax proteins were analysed immunohistochemically. The superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px) and malondialdehyde (MDA) activity levels in the testis tissue were also measured. The superoxide dismutase activity and malondialdehyde levels in the torsion group were significantly higher than those of the sham group (P < 0.05). Thymoquinone administration significantly reduced these levels. Torsion significantly increased active‐Caspase 3 and Bax expression, which was decreased by thymoquinone. The apoptotic index of the torsion group was significantly higher than that of the control group. However, thymoquinone significantly reduced the apoptotic index (P < 0.05). Our results indicate that thymoquinone plays a protective role in oxidative stress induced ischaemia–reperfusion in the testis tissue of rats.     

The protective effect of erythropoietin infusion on testicular torsion/detorsion: an experimental study

Introduction  The aim of the present study was to evaluate the effects of erythropoietin (EPO) on the histopathology of testes after unilateral testicular torsion and detorsion. Materials and methods  Twenty-five male Sprague–Dawley rats weighing 120 g were used in this study. The rats were randomly divided into three groups, a sham group consisting of five rats and the other two groups consisting of ten rats. In group 1 (sham group), right orchiectomy with no additional intervention was performed. In group 2 (T/D group), torsion was created by rotating the testis 720° in a clockwise direction for 4 h. After a 4-h torsion period, the right testis was detorted and replaced into the scrotum for 4 h. After the torsion, 0.5 cc 0.9% NaCl solution was injected once and three times in a week (total 12 doses). In group 3 (T/D + erythropoietin; EPO group), the same surgical procedure was done as in group 1, but EPO 1,000 IU/kg was injected just before the detorsion and three times in a week. At the end of each procedure, bilateral orchiectomies were performed for the histopathological examinations in all groups. Results  We examined the testes weight, vascularization of the region between the seminiferous tubules, percentage of necrotic seminipherous tubules, and maturation of spermatogenesis in terms of necrosis, sertoli cells, maturation arrest of spermatogenesis, hypospermatogenesis, and normal spermatogenesis of torsioned testis tissues with and without EPO treatment. Extremely significant differences in testicular weight were observed in group 1 compared to groups 2 and 3 (P < 0.001). Conclusion  Administration of EPO significantly influenced the rescue of testicular function by preserving the intact seminiferous tubular morphology, lowering the percentage of necrotic seminipherous tubules, and significantly reducing histological damage (P < 0.05).     

Protective effects of dexmedetomidine on ischaemia-reperfusion injury in an experimental rat model of priapism

The study aimed to investigate the effects of dexmedetomidine against ischaemia-reperfusion injury occurring after priapism in a model of induced-priapism in rats. A total of 18 male rats were randomised into three groups. Group 1 was the control group. A priapism model was performed rats in Group 2 and then ischaemia-reperfusion injury was evaluated. Group 3 had similar procedures to the rats in Group 2. Rats in Group 3 additionally had 100 μg/kg dexmedetomidine administered intraperitoneally immediately after reperfusion. Blood and tissue samples were analysed. Biochemical analysis of blood samples revealed a decrease in the levels of the pro-inflammatory cytokines including interleukin-1 beta (IL-1 Beta), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha) in Group 3 compared to Group 2 (p:.04, p:.009 and p:.009, respectively). Similarly, the highest malondialdehyde (MDA) level was in Group 2 (p:.002). The levels of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were significantly higher in Group 3 than that of Group 2 (p:.037 and p:.045, respectively). Direct microscopic examinations revealed positive changes in desquamation, oedema, inflammation and vasocongestion scores in Group 3 compared to Group 2 (p:.007, p:.008, p:.007 and p:.006, respectively). Dexmedetomidine has a protective effect against ischaemia-reperfusion injury in penile tissue.     

Predictive value of ischaemia-modified albumin in spermatogenesis in an experimental testicular torsion model

Our aim was to measure the ability of ischaemia-modified albumin (IMA) to predict testicular histopathological damage in the testes of rats with short- and long-term ischaemia using experimental testicular torsion and subsequent reperfusion via detorsion.21 Wistar Albino rats were randomized into three groups. The sham group was subjected to a mid-scrotal incision only. The 4- and 8-hr T/D (Torsion/Detorsion) groups were subjected to left testicular torsion by twisting the testes by 720 degrees counterclockwise. 2 cc venous blood samples were taken from the sham group after the mid-scrotal incision, and from the 4- and 8-hr T/D groups after 4 and 8 hr respectively. After that, the 4- and 8-hr T/D groups were subjected to detorsion. Two days later, orchiectomy was performed. Ischaemia-modified albumin levels were significantly different among the groups at 48 hr prior to orchiectomy (reperfusion; p = .003). Based on the results of the paired comparisons, it was found that IMA levels of the sham group were significantly higher than those of the 4- and 8-hr T/D groups (p = .002 and .009 respectively). Our study has showed that IMA may be used to predict ischaemia/reperfusion injury, which is another complication that may occur following detorsion in testicular torsion.     

Effects of myricetin on testicular torsion-detorsion injury in rats

Testicular torsion is an emergency, and unless there is an urgent intervention, irreversible ischaemic damage and gonad loss occur in the testicle. We aimed to investigate myricetin's antioxidant properties as well as its protective effect against ischaemia–reperfusion (I/R) damage in the testicular torsion model. A total of 18 rats were divided into three equal groups. Group 1 was the sham group. Group 2: testicular torsion was performed, and orchiectomy was done 2 hr after detorsion. Group 3: received torsion and 1 mg/kg intraperitoneal myricetin was given 30 min before detorsion, and orchiectomy was applied 2 hr after detorsion. We evaluated tissue malondialdehyde, superoxide dismutase, and catalase levels and Johnsen Testicular Biopsy Score to show its histopathological effect. There was a statistically significant decrease in MDA values in myricetin group compared to Group 2 (p < .017). There was no significant difference in the statistical analysis of SOD and CAT values (p = .337 and p = .025). There was a statistically significant difference in testicular I/R damage in the myricetin group compared to Group 1 and Group 2 (p < .017). Myricetin treatment significantly decreased testicular tissue damage compared to the torsion group but did not reach the values close to the control group.     

The protective effect of Cold-inducible RNA-binding protein (CIRP) on testicular torsion/detorsion: An experimental study in mice

Purpose

To evaluate the expression of Cold-inducible RNA-binding protein (CIRP) in torsion/detorsion of the testes in different phases and demonstrate the protective effect of CIRP on testicular injury after torsion/detorsion (T/D) in an experimental mouse model.

Methods

Twenty-four male BALB/c mice were divided randomly into 8 groups: normal control group (N), sham-operated group (S), torsion 2 h group (T2h), torsion/detorsion 12 h group (T/D12h), and T/D24h, T/D48h, T/D72h, and T/D96h groups. The testes were examined for the expression levels of CIRP. Another 32 male BALB/c mice were divided randomly in to 4 groups: normal control group (N), T/D group, T/D + pcDNA3.1 group, and T/D + pcDNA3.1-CIRP group. The plasmids were transfected into testes with in vivo-jetPEI. After 3 days, morphological changes, mean seminiferous tubule diameter (MSTD), and the number of the germ cell layers were observed. Superoxide dismutase (SOD) activity, the levels of malondialdehyde (MDA), and Bcl-2/Bax ratios were studied in the different groups.

Results

Compared with the N and S groups, the expression of CIRP in the T2h group was down-regulated. In T/D groups, the levels of CIRP were reduced in a time dependent manner. Compared to T/D and T/D + pcDNA3.1 group, the MSTD, number of the germ cell layers, SOD activity, and Bcl-2/Bax ratio increased in T/D + pcDNA3.1-CIRP group, while the level of MDA decreased.

Conclusions

The results of our study have shown that down-regulated CIRP is involved in testicular injury after testicular torsion/detorsion. Up-regulation of the expression of CIRP may reduce the damage caused by torsion/detorsion, possibly by preventing germ cell oxidative stress and apoptosis.     

Sitagliptin protects male albino rats with testicular ischaemia/reperfusion damage: Modulation of VCAM-1 and VEGF-A

Twisting of the spermatic cord is considered a popular problem in the urological field, which may lead to testicular necrosis and male infertility. Sitagliptin, a glucose-lowering agent, proved to have a vindicatory function in myocardial and renal ischaemia/reperfusion (I/R), but its role in testicular I/R has not yet been studied. The current work investigates its capability to recover the testicular I/R injury with shedding more light on the mechanism of its action. Four groups were used: sham, sham pretreated with sitagliptin, I/R and sitagliptin/I/R-pretreated groups. The outcomes proved that I/R significantly decreased the serum testosterone, with a major increase in oxidative, inflammatory and nitrosative stress, along with a reduction in testicular vascular endothelial growth factor-A level with marked germinal cell apoptosis. However, pretreatment with sitagliptin significantly reversed the profound testicular I/R damaging effects, on the basis of its antioxidant, anti-inflammatory and anti-apoptotic activities with the ability of recuperation of the testicular vascularity.     

Achillea millefolium alleviates testicular damage in paclitaxel-intoxicated rats via attenuation of testicular oxido-inflammatory stress and apoptotic responses

The aim of this study was to investigate the effects of Achillea millefolium extract in paclitaxel-induced testicular toxicity in rats. The groups were designed as (1) control, (2) paclitaxel (8 mg/kg, intraperitoneally), (3) paclitaxel (8 mg/kg, intraperitoneally) + Achillea millefolium (200 mg/kg, orally for 14 consecutive days) and (4) paclitaxel (8 mg/kg, intraperitoneally) + Achillea millefolium (400 mg/kg, orally for 14 consecutive days). Serum levels of testosterone, luteinising hormone and follicle-stimulating hormone, as well as total antioxidant capacity and total oxidant status were measured one day after receiving the last dose of Achillea millefolium extract. Testicular superoxide dismutase activity, malondialdehyde, tumour necrosis factor alpha and interleukin-1β levels, the expressions of nuclear factor kappa B and caspase-3 were evaluated. In addition, testicular sections were evaluated histopathologically and 8-hydroxy-2′-deoxyguanosine was detected immunohistochemically. Achillea millefolium improved the levels of luteinising hormone, follicle-stimulating hormone and testosterone, upregulated testicular antioxidant enzymes and downregulated inflammation. Furthermore, we observed that Achillea millefolium restored testicular histopathological structure and significantly suppressed oxidative DNA damage and apoptosis by reducing the expression of caspase-3. Taken together, our results suggest that Achillea millefolium has protective effects against paclitaxel-induced testicular toxicity and is a promising natural product with the potential to improve male fertility.