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

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

Ginkgo biloba extract (EGb 761) mitigates methotrexate-induced testicular insult in rats: Targeting oxidative stress, energy deficit and spermatogenesis.

Methotrexate (MTX) is commonly used as a therapeutic agent in the treatment of malignancies and autoimmune disorders. Risk of subsequent infertility following MTX administration has been reported as a significant side effect due to testicular toxicity. The aim of the study was to evaluate the modulatory effects of Ginkgo biloba (standardized extract, EGb 761) on MTX-induced testicular oxidative stress, energy deficits and spermatogenic status in rats. All groups received intraperitoneal injection of MTX (0.5 mg/kg) twice weekly for four weeks except the control group that received the corresponding vehicles. Other groups received oral EGb761, at doses 25, 50 or 100 mg/kg/day, for four weeks, concurrently with MTX. Blood and semen sampling followed by testis dissection were performed 24 h after last EGb 761 treatment. Semen was examined for sperm progressive motility, percent of normal spermatozoa and sperm cell concentration as well as seminal plasma essential and non-essential amino acids. Serum LH, FSH and testosterone were detected as well as testicular MDA, GSH, GSSG, TNF-α, IL-1ß, IL-6, NF-κB and the nuclear, cytoplasmic and mRNA expression levels of Nrf-2 besides the testicular cell energy; AMP, ADP and ATP. Histopathological studies of interstitial fibrosis and the severity of germ cell degeneration were also conducted. MTX induced significant decline in sperm quality along with decreased essential and non-essential amino acids in seminal plasma. MTX reduced serum FSH, LH and testosterone as well as testicular ATP, GSH and Nrf2, while increased levels of testicular ADP, AMP, MDA, GSSG and TNF-α. Results were confirmed by prominent interstitial fibrosis and severe germ cell degeneration in MTX group. Concurrent treatment with EGb 761 alleviated MTX-induced testicular insult evidenced by amelioration of oxidative stress biomarkers, energy functions, seminal sperms abnormalities and spermatogenesis status. The present study suggests a beneficial role of EGb 761 in MTX-induced testicular injury and subsequent distortion of spermatogenesis.

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

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

Antioxidant, anti-inflammatory and anti-apoptotic effects of hydro-ethanolic extract of Cyperus esculentus L. (tigernut) on lead acetate-induced testicular dysfunction in Wistar rats.

AIM: Lead acetate impairs testicular function by enhancing testicular oxidative stress and apoptosis. Cyperus esculentus possesses antioxidants and has shown great improvement of testicular function. This study investigated the protective effect of hydro-ethanolic extract of Cyperus esculentus on lead acetate-induced testicular dysfunction in Wistar rats. MATERIALS AND METHODS: Twenty-five male Wistar rats (180-195 g) were randomly divided into 5 groups (n = 5) namely: Normal control (NC), Lead control (PbC) (20 mg/kg b.w. i.p.), C. esculentus-treated (CE) (500 mg/kg b.w p.o.), Pb + CE(500) (20 mg/kg of lead and 500 mg/kg of extract) and Pb + CE(1000) (20 mg/kg of lead and 1000 mg/kg of extract). Administration lasted for 21 days. RESULTS: Sperm count, motility, viability, serum testosterone and follicle stimulating hormone, Johnsen's score, Leydig cell count, Sertoli cell count, testicular testosterone, B-cell lymphoma protein-2 (Bcl-2), steroidogenic acute regulatory protein, cytochrome P450 A1, 3ß-hydroxysteroid dehydrogenase (HSD), 17ß-HSD, enzymatic antioxidant activities and total antioxidant capacity were significantly (p < 0.05) decreased in PbC compared with NC. These parameters however increased significantly (p < 0.05) in Pb + CE(500) and Pb + CE(1000) compared with PbC. Lead acetate upregulated (p < 0.05) testicular malondialdehyde, nitric oxide, glucose, lactate, lactate dehydrogenase, C-reactive protein, tumor necrosis factor-α, interleukin (IL)-6, IL-1ß, Bcl-2 associated X (Bax), Bax/Bcl-2 and cleaved caspase-3 levels. All these parameters were downregulated (p < 0.05) in Pb + CE(500) and Pb + CE(1000) in comparison with PbC. CONCLUSION: C. esculentus exhibited a dose-dependent mitigation of lead acetate-induced testicular dysfunction in Wistar rats via its antioxidant, anti-inflammatory and anti-apoptotic effects.

Protective effect of Polygonatum sibiricum against cadmium-induced testicular injury in mice through inhibiting oxidative stress and mitochondria-mediated apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonatum sibiricum (PS), the dried rhizome of the liliaceous plant including P. sibiricum Red., P. cyrtonema Hua. and P. kingianum Coll. et Hemsl., is a widely used Chinese herbal medicines. It was first published in "Special Records of Famous Doctors", in which is described to replenished Qi and nourish Yin, strengthening the spleen and nourishing the lungs and kidney. Based on the principle of kidney controlling the reproduction, kidney-tonifying therapy has traditionally been seen as most applicable to the treatment of infertility. The current investigation has focused on the protective effect of PS against cadmium-induced testicular injury in mice. AIM OF THE STUDY: To investigate the protective effect of PS against cadmium-induced testicular injury in mice via the TXNIP-NLRP3-Caspase-1 and CytC-Caspase-9-Caspase-3 pathways. MATERIALS AND METHODS: PS was processed into Polygonatum sibiricum aqueous extract (PSAE). A mouse testicular injury model was established by a single intraperitoneal (i.p.) injection of cadmium chloride (CdCl2) (2.5 mg/kg b.w.), and the mice were treated intragastrically with PSAE (10 g/kg b.w.) once daily for 35 consecutive days. At the end of the experiment blood and testicular tissue samples were collected to analyze sperm survival rate and sperm deformity rate, serum testosterone T content, testicular oxidation related indicators levels (SOD, MDA, GSH, CAT) in testicular tissue, and histopathological changes of testicular tissues. The testicular cell cycle and reactive oxygen species (ROS) levels were measured by flow cytometry, the expression levels of thioredoxin-interacting protein (TXNIP), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase-1, interleukin (IL)-1ß, Cyctochrome C (CytC), Caspase-3, and Caspase-9 mRNA in testicular tissue were detected by qRT-PCR and the protein expression levels of TXNIP, NLRP3, Caspase-1, CytC, Caspase-3, and Caspase-9 were detected by Western blot and immunohistochemical method. RESULTS: The results indicated that compared with the model group, PSAE brought testicular weight to a near-normal range, improved sperm survival rate and reduced sperm abnormality rate, elevated the level of testosterone, made the damaged testis tissue recover to near normal, reduced the level of ROS, and inhibited testicular cell apoptosis. Further study showed that PSAE significantly decreased the levels of relative genes and proteins in testicular cells, such as TXNIP, NLRP3, Caspase-1, IL-1ß, CytC, Caspase-3, and Caspase-9, which suggested that PSAE could regulate oxidative stress through the TXNIP-NLRP3-Caspase-1 signaling pathway, and inhibit apoptosis in the mitochondrial pathway via CytC-Caspase-9-Caspase-3 pathway. In summary, we have confirmed that PSAE exerted a powerful protective effect on CdCl2-induced testicular injury in mice through inhibiting oxidative stress and mitochondria-mediated apoptosis.

Un-riped fruit pods of Prosopis cineraria (L.) Druce ameliorates Cisplatin therapy-induced partial testicular atrophy in male Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Prosopis cineraria (L.) Druce is a plant that is widely found in dry parts of India. The unripe fruit pod has a very specific traditional claim of treating male infertility and increasing sperm volume and count. AIM: The present work was endeavored to investigate the long-standing traditional claim of P. cineraria on meliorating male fertility. The study focussed on cancer therapy-induced male infertility and curative effect of the extract with an appraisal on any possible revitalizing effects on sperm count, morphology, motility, and viability combined with hormonal and histopathological investigations. MATERIALS AND METHODS: Male Wistar rats were used for the study. Two different doses of 400 mg/kg/d and 800 mg/kg/d (both p.o.) of the Hydroalcoholic extract were chosen as test dose while Clomiphene (25 mg/kg/d; p.o.) treatment served as standard treatment. Animals were initially injected with cisplatin (1 mg/kg/d; i.p.) for 15 days and the drug treatment was begun at the 16th day and continued till 43rd day (28 days treatment). Later all male animals got cohabited with female animals in the ratio 1:3. On confirmation of mating, female animals were isolated. Male animals were euthanized on batches. Testis and epididymis were weighed and homogenized. Sperm count, motility, morphology, viability, and headcount. The serum collected was evaluated for serum FSH, LH, and testosterone levels. On day Gestational day 15, gravid uterus observations were calculated to evaluate male and female fertility parameters. RESULTS: There were statistically significant improvements (p < 0.001) in sperm motility, sperm count, sperm viability, and improved morphological features. The same pace was also noticed in testosterone, FSH and LH levels in serum and LPO, CAT, GSH, GPx and SOD in testicular tissues. The extract treated male animals produced better and healthy litter compared to cisplatin-treated animals with less pre- and post-implantation loss. CONCLUSION: Consolidating the results seen, the extract ameliorated the testicular toxicity caused by cisplatin in a dose-dependent manner. Further insight and evaluation of the phytochemicals of the pods should be performed to bring up commercial viability.

Pomegranate Seeds Extract Possesses a Protective Effect against Tramadol-Induced Testicular Toxicity in Experimental Rats.

Tramadol is a centrally acting opioid analgesic that is extensively used. The chronic exposure to tramadol induces oxidative stress and toxicity especially for patients consuming it several times a day. Previously, we and others reported that tramadol induces testicular damage in rats. This study was conducted to investigate the possible protective effect of pomegranate seed extract (PgSE) against tramadol-induced testicular damage in adult and adolescent rats. Male rats were orally treated with tramadol or in a combination with PgSE for three weeks. Testes were then dissected and analyzed. Histological and ultrastructural examinations indicated that tramadol induced many structural changes in the testes of adult and adolescent rats including hemorrhage of blood vessels, intercellular spaces, interstitial vacuoles, exfoliation of germ cells in lumen, cell apoptosis, chromatin degeneration of elongated spermatids, and malformation of sperm axonemes. Interestingly, these abnormalities were not observed in tramadol/PgSE cotreated rats. The morphometric analysis revealed that tramadol disrupted collagen metabolism by elevating testicular levels of collagen fibers but that was protected in tramadol/PgSE cotreatment at both ages. In addition, DNA ploidy revealed that S phase of the cell cycle was diminished when adult and adolescent rats were treated with tramadol. However, the S phase had a normal cell population in the cotreated adult rats, but adolescent rats had a lower population than controls. Furthermore, the phytochemistry of PgSE revealed a high content of total polyphenols and total flavonoids within this extract; besides, the DPPH free radical scavenging activity was high. In conclusion, this study indicated that PgSE has a prophylactic effect against tramadol-induced testicular damage in both adult and adolescent ages, although the tramadol toxicity was higher in adolescent age to be completely protected. This prophylactic effect might be due to the high antioxidant compounds within the pomegranate seeds.

Costus afer leaf extract protects against testicle damage caused by cyclosporine A in adult male Wistar rats through an antioxidant mechanism.

Cyclosporine A is one of the most widely used drugs in organ transplant and oncology patients. But its use is accompanied by many toxicities. This study aimed to investigate the possible protective effect of Costus afer (C. afer) leaf extract on cyclosporine A-induced testicular toxicity. This study was carried out on 40 adult male Wistar rats were divided into four groups: control, C. afer, cyclosporine A and cyclosporine A+ C. afer groups. The investigations include genital weight, sperm count and characters, serum luteinising hormone (LH) and testosterone, testicular tissue contents of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) and lipid peroxidation (MDA). Besides, a histopathological examination of testicular tissue stained with haematoxylin and eosin (H & E) was performed. Cyclosporine A+ C. afer group showed a significant increase in the genital weight, serum testosterone, sperm count, motility and viability. Besides, the extract significantly decreased testicular content of MDA and increased SOD, CAT and GSHPx. C. afer coadministration significantly decreased serum LH and sperm abnormalities and protected against testicular histopathological alterations. The extract showed a protective effect against testicular toxicity associated with cyclosporine A and that was through an antioxidant mechanism.

Studies on the phytomodulatory potential of fenugreek (Trigonella foenum-graecum) on bisphenol-A induced testicular damage in mice.

Bisphenol A (BPA), an organic synthetic compound and endocrine disruptor, which majorly cause deleterious effects on male reproductory system. Fenugreek (Trigonella foenum-graecum), associated with Leguminosae family is used as a herbal medicine with potent antioxidant properties. The present study was aimed to scrutinise the preventative role of fenugreek seeds aqueous extract (FSEt) on BPA-induced testicular damage in mice. Study included four different groups of male Balb/c mice: contol (C), fenugreek (FSEt), bisphenol A (BPA) and fenugreek + bisphenol A (FSEt + BPA). After two months of treatment, assessment of sperm parameters, antioxidant defence system, histopathological studies, germ cell count and gene expression of intrinsic apoptotic pathway were carried out. Administration of FSEt improved the damage caused by BPA as indicated by improved sperm parameters. FSEt-administered mice showed improvement in the histoarchitecture compared with BPA-administered animals. In addition, fenugreek treatment showed reduced levels of malondialdehyde and elevated levels of antioxidant enzymes. Expression studies of apoptotic markers revealed a significant decrease in the expression of Bcl-2 and significant increase in caspase-9 and caspase-3. However, FSEt restored the deleterious effects caused by BPA. The current findings plausibly might have promising protective role against BPA-induced testicular damage.

Metformin decreases testicular damages following ischaemia/reperfusion injury in rats.

The effects of metformin on a testicular torsion injury in adolescent rat testis after I/R were evaluated in the present study. Forty adolescent rats were divided into five groups with eight rats per group: a control group; a sham-operated group; an ischaemia group, where torsion was applied for 4 hr and testis was examined immediately after detorsion; an I/R group, where torsion was applied for 4 hr and the testis was examined 4 hr after detorsion; and an I/R + M group, where the metformin (300 mg/kg) administration was added to the identical procedures used for the I/R group. Spermatogenesis, basal membrane integrity and cleaved caspase-3 expression were assessed. The I/R + M group had a significantly higher Johnsen score than the I/R group (7.9 ± 0.1 vs. 7.5 ± 0.2; p < .001; F-value = 14.2). Failure of basal membrane integrity was highest in the ischaemia group (45 ± 5) compared to the other groups (control group, 20 ± 5; sham-operated group, 16.6 ± 2.8), but not different between the I/R + M (31.6 ± 12.5) and the I/R groups (25 ± 3.5). Cleaved caspase-3 expression was highest in the ischaemia group (73.5 ± 0.7), and significantly lower in the I/R + M group (33.4 ± 0.9) than the I/R group (58.5 ± 0.2; p < .05; F-value = 7.6). Metformin decreases testicular damage by exerting protection against the harmful effects of I/R on spermatogenesis and alleviating apoptosis in adolescent rat testis.

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.

Protective efficiency of Ashrasi date palm hydroalcoholic extract against diabetes-induced testicular toxicity: A biochemical and stereological study.

The present study was designed to investigate the protective effects of hydroalcoholic extract of Ashrasi date palm (ADP) on diabetes-induced testicular injuries. Adult male rats were randomly allocated into five groups (n = 8 in each group): 1: control; 2: diabetic; 3: diabetic + 30 mg/kg of ADP extract; 4: diabetic + 90 mg/kg of ADP extract; and 5: diabetic + 270 mg/kg of ADP extract. Diabetes was induced by a single dose of streptozotocin (55 mg/kg) intraperitoneally. Testicular changes were assessed quantitatively using stereological method followed by measuring antioxidant enzymes including catalase, superoxide dismutase and glutathione peroxidase and serum testosterone level. Malondialdehyde (MDA) and Bcl-2 expression were also evaluated in tissue samples. Diabetes resulted in significant deleterious alterations in the architecture of testicular tissue, suppressed antioxidant enzymes and testosterone levels and increased lipid peroxidation. The expression of Bcl-2 was downregulated in diabetic testis and resulted in enhanced apoptosis. Eight weeks of ADP extract treatment especially at higher doses could markedly improve structural changes of testis and restore the antioxidant defence and testosterone levels in testicular tissue. In conclusion, this findings showed that ADP extract can play as a potent antioxidant and can attenuate the adverse effects of diabetes on male reproduction.

The preventive role of wheat germ oil against sertraline-induced testicular damage in male albino rats.

Sertraline is an antidepressant medication used extensively in the therapy of depression. The present investigation was intended to estimate the actual protective role of wheat germ oil on sertraline-caused testicular injury in albino rats. Sertraline (human therapeutic dose, 15.63 mg/kg) was orally administrated to rats for 28 successive days. Sertraline-administered rats were concurrently supplemented with wheat germ oil (human therapeutic dose, 68.75 mg/kg) for 28 successive days. Sertraline administration induced an elevation in testicular DNA damage and acute testicular damage illustrated by the histopathological alterations including marked degeneration and necrosis of germ cells lining seminiferous tubules, as well as interstitial oedema, congestion of interstitial blood vessel. Wheat germ oil administration potentially mitigated the histopathological alterations of sertraline-administered rats. Lipid peroxidation, oxidative stress biomarker, showed a significant elevation in testicular tissue of sertraline-administered rats. Furthermore, glutathione content and catalase activity were decreased in testicular tissue of sertraline-administered rats. Serum testosterone level was elevated in sertraline-administered rats. Wheat germ oil significantly reduced lipid peroxidation of testicular tissue and improved the antioxidant defences. Finally, wheat germ oil has a preventive role against testicular damage induced by sertraline in rats probably via its potential to prevent reactive oxygen species.

Treatment with melatonin and selenium attenuates docetaxel-induced apoptosis and oxidative injury in kidney and testes of mice.

Docetaxel (DTX) has been used in cancer treatments for several decades, but it results in many adverse apoptotic effects through excessive production of reactive oxygen species (ROS) in some tissue including the kidney and testes. We aimed to investigate potential modulatory roles of melatonin (MEL) and selenium (Se) against DTX-induced apoptosis and oxidative injury in the testes and kidney of mice. Thirty-two mice were divided into four equal groups as control, DTX, DTX + MEL and DTX + Se. DTX group was treated with a single intraperitoneal dose of DTX. After DTX treatment, MEL and Se were administered to the mice in the DTX + MEL and DTX + Se groups for 7 days respectively. Increased lipid peroxidation, ROS, apoptosis, caspase-3 and caspase-9 activities in the kidney and testes of the DTX group were diminished by treatment with MEL and Se. DTX-induced decreases in vitamin E (α- and γ-tocopherol), glutathione peroxidase and reduced glutathione levels in the kidney and testis were increased following MEL and Se treatments. In conclusion, our data show that MEL and Se can act as modulators against DTX-induced apoptosis and oxidative damage in the kidney and testis through up-regulation of glutathione and vitamin E and down-regulation of caspase pathways.

Testicular microanatomical and hormonal alterations following use of antiretroviral therapy in Sprague Dawley rats: Role of Naringenin.

Human immunodeficiency virus-infected man may require assisted reproductive technology not just for safer conception but also due to subfertility. The study investigated the effect of antiretroviral drugs on the fertility potentials of males and the possible protective role of Naringenin, using Sprague Dawley rats. Thirty adult male Sprague Dawley rats were grouped into-A: Distilled water; B: Highly Active Antiretroviral Therapy (HAART); C: Naringenin 40 mg/kg; D: Naringenin 80 mg/kg, E: HAART + Naringenin 40 mg/kg; F: HAART + Naringenin 80 mg/kg. The rats were euthanised after 10 weeks. Results showed a significant decrease in sperm count in group B when compared to the control and other groups. Spermatozoa with normal morphology also reduced significantly in the B group and progressive sperm motility reduced when compared to the control, D and the F group. The serum testosterone was not significantly different between groups A and B, however the groups C and D displayed significant increase when compared to groups A and B. The serum luteinising hormone was significantly higher in group B when compared to groups A, E and F. Our data suggest that Naringenin improves the male reproductive anatomy and function, therefore, it promises to be a beneficial adjuvant for mitigating HAART testicular and reproductive perturbations.

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

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

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

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

Silymarin and celecoxib ameliorate experimental varicocele-induced pathogenesis: evidences for oxidative stress and inflammation inhibition.

BACKGROUND: The present study was done to investigate the ameliorative effect of silymarin (SMN) and celecoxib (CEL) on varicocele (VCL)-induced detrimental impact in testicular tissue. METHODS: Mature Wistar rats were divided into control and test groups. Following VCL induction, the animals in test group were subdivided into non-treated VCL-induced, SMN-treated (50 mg/kg, orally), CEL-treated (10 mg/kg) and SMN + CEL-treated groups. Following 60 days, testicular total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), total thiol molecules (TTM), mRNA and protein levels of COX2 and mRNA level of iNos were analyzed. Moreover, the germinal cells apoptosis and mRNA damage were examined. RESULTS: Observations revealed that co-administration of SMN and CEL significantly (P < 0.05) up-regulated TAC, SOD, GSH-px and TTM levels and resulted in a remarkable (P < 0.05) reduction in iNos and COX2 expression, NO and MDA contents. The animals in SMN + CEL-treated group exhibited significantly (P < 0.05) lower number of apoptotic cells and cells with mRNA damage per one mm2. CONCLUSION: The SMN by up-regulating testicular TAC, SOD, GSH-px and TTM levels and the CEL by inhibiting COX2 and iNos expression as well as NO content could fairly ameliorate the VCL-decreased spermatogenesis.

Attenuation of Sulfite-Induced Testicular Injury in Rats by Zingiber officinale Roscoe.

Sulfite salts, including sodium metabisulfte, are widely used as preservatives in foods and pharmaceutical agents. Previous studies suggest that oxidative stress may be an important mediator of testicular injury. The present study was designed to elucidate the effect of exposure to sodium metabisulfite by gavage without or with Zingiber officinale (ginger) extract on the rat testes. Thirty-two male Wistar rats were randomly divided into control, ginger-treated (500 mg/kg/day), sodium metabisulfite- (SMB-) treated (260 mg/kg/day), and SMB + ginger- (SZ-) treated groups. After 28 days, the rats were anesthetized by ether and, after laparotomy, blood was collected from the heart to determine testosterone level by the enzyme-linked immunosorbent assay (ELISA) kit. Then left testes and cauda epididymis of all animals were removed for histological examination and sperm analysis, and right testes were removed for assessing lipid peroxidation (indexed by malondialdehyde [MDA]) and antioxidant enzymes. The results showed that spermatogenesis, epididymal morphometry, and sperm parameters were affected by SMB. There was a significant increase in MDA level and a significant reduction in the activities of glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) in the SMB-treated rats compared to the control. Ginger treatment of SMB-exposed rats significantly increased testosterone level and the number of different spermatogenic cells. The level of MDA reversed to the control levels and the activities of GPx and GR were significantly increased when SMB was coadministered with ginger extract. It is concluded that coadministration of ginger, through its antioxidant and androgenic properties, exerts a protective effect against SMB-induced testicular oxidative stress.

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

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