Edible wild plants, chicory and purslane, alleviated diabetic testicular dysfunction, and insulin resistance via suppression 8OHdg and oxidative stress in rats.

Testicular dysfunction is a prevalent health problem frequently reported in individuals with diabetes mellitus (DM). Oxidative-inflammatory reactions, hormonal and spermatic abnormalities often accompany this illness. Herbal remedies "particularly wild plants" including chicory (Chicorium Intybus) and purslane (Portulaca Oleracea) are emerging as popular agents for people dealing with these issues due to their ability to act as antioxidants, reduce inflammation, and exhibit antidiabetic effects. According to the collected data, the daily administration of chicory (Ch) seed-extract (250 mg/kg) or purslane (Pu) seed-extract (200 mg/kg) to streptozotocin (STZ)-induced diabetic rats (50 mg/kg) for 30 days resulted in the normalization of fasting blood glucose (FBG), serum fructosamine, insulin levels, and insulin resistance (HOMA-IR), as well as reducing lipid peroxidation end-product malondialdehyde (MDA) level, aldehyde oxidase (AO) and xanthene oxidase (XO) activities. While caused a considerable improvement in glutathione (GSH) content, superoxide dismutase (SOD), catalase (CAT) activity, and total antioxidant capacity (TAC) when compared to diabetic rats. Ch and Pu extracts had a substantial impact on testicular parameters including sperm characterization, testosterone level, vimentin expression along with improvements in body and testis weight. They also mitigated hyperlipidemia by reducing total lipids (TL), total cholesterol (TC) levels, and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C). Furthermore, oral administration of either Ch or Pu notably attuned the elevated proinflammatory cytokines as tumor necrotic factor (TNF-α), C-reactive protein (CRP), and Interleukin-6 (IL-6) together with reducing apoptosis and DNA damage. This was achieved through the suppression of DNA-fragmentation marker 8OHdG, triggering of caspase-3 immuno-expression, and elevation of Bcl-2 protein. The histological studies provided evidence supporting the preventive effects of Ch and Pu against DM-induced testicular dysfunction. In conclusion, Ch and Pu seed-extracts mitigate testicular impairment during DM due to their antihyperglycemic, antilipidemic, antioxidant, anti-inflammatory, and antiapoptotic properties.

Zhibai Dihuang Pill Alleviates Ureaplasma urealyticum-Induced Spermatogenic Failure and Testicular Dysfunction via MAPK Signaling Pathway.

The testicles and sperm are extremely susceptible to inflammation and oxidative stress. Although Zhibai Dihuang Pill (ZDP) has been reported to treat various infertilities including male infertility induced by Ureaplasma urealyticum (UU) infection, its mechanism is still poorly understood. This study is aimed at clarifying the underlying mechanism of ZDP to protect against UU-infected male infertility. We found that UU-infected infertile rats exhibited weight loss, reduced food intake, and decreased sperm count and vitality. The administration of ZDP improved the general state and sperm motility of rats. In addition, UU infection led to spermatogenesis disorders, impaired secretory function and blood-testis barrier (BTB) of Sertoli cells, and elevated inflammation and oxidative stress. As expected, ZDP suppressed inflammation and oxidative stress to alleviate spermatogenesis disorders. Our research showed that ZDP could improve spermatogenesis disorders and testicular function primarily through the mitogen-activated protein kinase (MAPK) signaling pathway. ZDP exerts its anti-inflammatory and antioxidant effects via the MAPK signaling pathway, thus playing an important role in ameliorating spermatogenesis failure and testicular dysfunction.

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.

GC-MS metabolomics reveals dysregulated lipid metabolic pathways and metabolites in diabetic testicular toxicity: Therapeutic potentials of raffia palm (Raphia hookeri G. Mann & H. Wendl) wine.

ETHNOPHARMACOLOGICAL RELEVANCE: Raffia palm (Raphia hookeri G. Mann & H. Wendl) wine (RPW) is a natural beverage obtained from the R. hookeri consumed for refreshment and medicinal purposes. For medicinal purposes, it is used singly or as macerating agent for other medicinal plants for the treatment of several diseases. AIM: This study investigates the effect of Raffia palm wine on dysregulated lipid metabolic pathways in testicular tissues of type 2 diabetic (T2D) rats. METHODS: Raffia palm wine (150 and 300 mg/kg bodyweight) was administered to two T2D groups respectively, another T2D group was not administered treatment and served as negative control, while metformin served as the standard drug. After 6 weeks of treatment, the rats were sacrificed, and the testes collected. After weighing, the organs were homogenized in 20% methanol/ethanol and centrifuged at 20,000 g to extract the lipid metabolites. RESULTS: GC-MS analysis of the supernatants revealed an alteration of the metabolites on induction of T2D, with concomitant generation of 10 metabolites. Raffia palm wine inhibited the T2D-generated metabolites while replenishing cholesterol and squalene levels, with concomitant generation of 7 and 8 metabolites for low and high dose treatment respectively. Pathway enrichment analysis of the metabolites revealed a decreased level of steroid biosynthesis and increased level of fatty acid biosynthesis. Raffia palm wine inactivated glycerolipid, fatty acid, and arachidonic acid metabolisms, fatty acid biosynthesis and fatty acid elongation in mitochondria pathways, and activated pathways for plasmalogen synthesis, mitochondrial beta-oxidation of long chain saturated fatty acids. CONCLUSION: The replenishment and generation of these metabolites and additional ones as well as activation of pathways involved in energy generation, phospholipids, antioxidant activity, steroidogenesis and spermatogenesis suggest a therapeutic effect of Raffia palm wine against hyperglycemic-induced testicular dysfunction.

Fluoride-induced testicular degeneration and sperm quality deteriorations: Salutary role of Cyperus esculentus tubers (tiger nut) extract in animal model.

OBJECTIVE: Chronic exposure to fluoride causes tissue damage induced by oxidative imbalance, Cyperus esculentus (CE) possess anti-inflammatory and immunostimulatory properties. This study focused on Salutary role of Cyperus esculentus in sodium fluoride (NaF) induced testicular degeneration and sperm quality deteriorations. METHODS: Sexually mature male Sprague-Dawley rats were randomly divided into four groups (n=6). Animals in control group received 2 mls of normal saline per day; CE group received 500mg/kg bw of CE; NaF group received 5mg/kg bw of NaF; NaF+CE group received 500mg/kg bw of CE (for 14 days pre-treatment) and NaF co-treatment till 56 days via gastric gavage. Parameters tested include: testicular histology, sperm parameters, sex hormone, fertility test, malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione, glutathione peroxidase (GPX), catalase (CAT), testicular fluoride and testicular cholesterol. RESULTS: Sodium fluoride significantly (p<.05) decrease testicular antioxidant (SOD, CAT, GSH and GPx), sperm quality, hormone profiles (TT, FSH, LH, estrogen levels), testicular cholesterol, morphometric parameters, Johnsen's Score and number of implantations in female rats with corresponding (p<.05) increase in oxidative stress makers and abnormal sperm morphology. Also depleted seminiferous epithelium and degenerate spermatogenic cells. Pretreatment with 500mg/kg bw of CE lowered NaF toxicity by significantly reducing the lipid peroxidation products, fluoride accumulation in the testis, histopathological changes of the testes and spermatozoa abnormalities and reverted observed NaF-induced inhibition in antioxidant parameters and weight of accessory sex organs. CONCLUSIONS: Cyperus esculentus attenuated NaF-induced testicular injuries and protected the seminiferous epithelium, reduced oxidative stress and promoted 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.

Cyclosporine A induces testicular injury via mitochondrial apoptotic pathway by regulation of mir-34a and sirt-1 in male rats: The rescue effect of curcumin.

Testicular damage contributes to cyclosporine A (CsA) induced male infertility. However, the exact underlying molecular mediators involved in CsA-induced testis disorder remains unclear. The present study aimed to characterize the role of mir-34a/sirt-1 in CsA induced testicular injury alone or in combination with curcumin. A total of twenty-eight male Wistar rats were subdivided into four groups: control (Con), sham, cyclosporine A (CsA), cyclosporineA + curcumin (CsA + cur). The animals received cyclosporine A (30 mg/kg) and curcumin (40 mg/kg) for 28 days by oral gavage. At the end of the experiment, CsA administration significantly resulted in a decrease in testis weight and testis coefficient. The molecular analysis demonstrated that CsA exposure increased 8-OHdg and Nox4 protein contents in the testis tissue. TUNEL staining indicated that CsA caused the number of apoptotic cells to increase in the testes of male rats. In addition, exposure to CsA resulted in an increased expression of Bax, and a decreased expresion in that of Bcl-2, with a concomitant up-regulation of the Bax/Bcl-2, c-Caspase-3/p-Caspase-3 ratio and cytochrome c level. Meanwhile, exposure to CsA increased the expression of mir-34a and decreased sirt-1 protein level in the testis tissue samples compared to the control group. Taken together, our findings suggested that CsA can cause damage to testicular germ cells via oxidative stress and mitochondrial apoptotic pathway, and probably mir-34a/sirt-1 play a crucial role in this process. It also demonstrates that these negative effects of CsA can be reduced by using curcumin as an antioxidant and anti-inflammatory agent.

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.

Correction of diabetes-induced testicular dysfunction by a hydro-methanol (60:40) extract of Curcuma amada rhizomes: A dose-dependent study.

Diabetes affects the reproductive system. This study was conducted to find out the potent dose of the hydro-methanol 60:40 extract of Curcuma amada rhizomes for the management of diabetes-induced testicular dysfunction in albino rats. The extract was administered at the doses of 10, 20, 40, and 80 mg/100 g body weight/day for 28 days. Oxidative stresses, reproductive parameters, histological, and gene expressions of the testicular tissue were assessed. Out of the doses used, the 20-mg dose showed maximum recovery as the minimum dose (e.g., sperm motility 112.03%, testicular cholesterol 34.86%, Bax gene expression 49.77%), whereas 40- and 80-mg doses did not vary statistically with each other (e.g., sperm motility 95.37% and 89.19%, testicular cholesterol 30.42% and 28.41%, Bax gene expression 47.33% and 46.18%, respectively) as well as with the 20-mg dose. It may be concluded that the 20-mg dose is the threshold dose for this purpose. PRACTICAL APPLICATIONS: The hydro-methanol 60:40 extract of rhizomes of Curcuma amada has a strong antioxidant property that can manage diabetes-induced oxidative injuries in testes which may raise a hope to the pharmaceutical industries to develop a herbal drug for diabetes-linked testicular hypofunction management.

High dose of standardised extract of Costus afer leaves potentiates cadmium reproductive toxicity in Wistar rats.

Protective effects of standardised extract of Costus afer leaves (CAME), an extract with good antioxidants on cadmium-induced reproductive toxicity in male rats, were investigated in this study. Forty-two adult male Wistar rats were randomly divided into six groups and were treated every day regularly for 4 weeks. G1 (control) rats received 1 ml of vehicle treatment. G2 rats were intoxicated with 2.5 mg kg-1  day-1 s.c cadmium chloride for 1 week. G3 and G4 rats were intoxicated with cadmium as in G2 rats and were treated orally with 100 and 200 mg/kg bwt/day of CAME, respectively, for 4 weeks. Group G5 and G6 rats were orally treated with 100 and 200 mg kg-1  day-1 bwt of CAME, respectively, for 4 weeks. Significant changes (p < 0.05) in andrological parameters (sperm count, sperm morphology, serum testosterone and nitric oxide concentration) and testicular antioxidant parameters (reduced glutathione, lipid peroxidation and activities of catalase, glutathione S-transferase and glutathione peroxidase) caused by Cd toxicity were improved in cadmium-intoxicated rats treated with 100 mg/kg body weight of CAME. Administration of 200 mg/kg body weight of CAME to cadmium-intoxicated rats potentiated reproductive toxic effects of cadmium. In conclusion, lower dose of CAME is preferred over high dose in treatment of cadmium-induced reproductive toxicity in rats.

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.

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.

Protective effect of Allium cepa (onion) seeds (AC) extract on histopathology of testis in STZ-induced male rats / Efecto protector del extracto de semillas de Allium cepa (cebolla) (AC) en la histopatología del testículo en ratas macho inducidas por STZ

SUMMARY: The aim of the present study was to evaluate the effect of the extract of Allium cepa (Onion) seeds (AC) on morphometric and histology of testis and biochemical parameters in STZ-induced male rats. Forty adult male Wistar rats (2 month old) were allocated into four groups of control, diabetic control, diabetic treated with 200 or 400 mg/kg/day of onion seed extract. Diabetes mellitus was induced using 60 mg/kg body weight of Streptozotocin as a single intraperitoneal injection. The extract was administered by stomach gavage for 28 days. The morphometric and histological structure of the testis, biochemical factors like glucose and testosterone levels were assessed. All analyses were done at the end of the four week study period. Data were compared by using Kruskal Wallis Test, Dunnett T3 and the degree of significance was set at P < 0.05 and P < 0.01. In diabetic+200 rats, the numbers of primary spermatocytes were significantly increased. In diabetic+400 rats, seminiferous tubular diameter was significantly increased and the level of testosterone hormone and testis weight was decreased significantly. In diabetic+200 and 400 rats, the numbers of spermatid, FBS and lumen diameter were significantly increased and the numbers of spermatozoa cells, body weight and volume density (VD) % lumen were decreased. Also, the numbers of spermatid in control diabetic rats was decreased. Our finding indicated that onion seed extract might be useful as a supplementary protective agent against adverse effects of diabetes on reproductive system in diabetic men.

RESUMEN: El objetivo del presente estudio fue evaluar el efecto del extracto de semillas de Allium cepa (cebolla) sobre la morfometría e histología de testículos y parámetros bioquímicos en ratas macho inducidas por estreptozotocina (STZ). Se asignaron cuarenta ratas macho Wistar adultas (2 meses de edad) en cuatro grupos: control diabético y diabético tratados con 200 o 400 mg / kg / día de extracto de semilla de cebolla. Se indujo diabetes mellitus utilizando 60 mg/kg de peso corporal de estreptozotocina por inyección única intraperitoneal. El extracto se administró por sonda gástrica durante 28 días. Se evaluaron la estructura morfométrica e histológica de los testículos, factores bioquímicos como la glucosa y los niveles de testosterona. Todos los análisis se realizaron al final del período de estudio de cuatro semanas. Los datos se compararon mediante el uso de Kruskal Wallis Test, Dunnett T3 y el grado de significación se estableció en P <0,05 y P <0,01. En el grupo diabético + 200, el número de espermatocitos primarios aumentó significativamente. En el grupo diabético + 400, el diámetro tubular seminífero aumentó significativamente en cambio el nivel de testosterona y el peso del testículo disminuyeron significativamente. En el grupo diabéticos + 200 y 400, los números de espermátidas, FBS y diámetro de luz se incrementaron significativamente y el número de espermatozoides, peso corporal y densidad de volumen (VD)% de lumen disminuyeron. Además, disminuyó el número de espermátidas en ratas diabéticas control. Nuestro estudio indicó que el extracto de semilla de cebolla podría ser útil como un agente protector adicional contra los efectos adversos de la diabetes en el sistema reproductivo en hombres diabéticos.

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.

Ameliorative role of ethyl-acetate fraction of methanolic leaf extract of Camellia sinensis (green tea) on streptozotocin-induced diabetes linked testicular hypofunction in albino rat: A dose-dependent biochemical and genomic transection study.

Background The present investigation focuses the diabetes-induced testicular hypofunction and its possible correction by the effective dose of ethyl-acetate fraction of methanolic extract of Camellia sinensis leaves through dose-dependent study in streptozotocin-induced diabetic rat. Methods The androgenic, spermiological, oxidative stress and apoptosis sensors along with testicular genomic sensors were evaluated in a dose-dependent fashion (50 mg or 100 mg or 200 mg/kg body weight). Activities of hepatic transaminases for toxicity assessment were also measured. Results Increased level of fasting blood glucose, testicular cholesterol, seminal vesicular fructose along with a low count, motility and viability of epididymal sperm, low activities of testicular Δ5, 3ß-hydroxy steroid dehydrogenase (HSD), 17ß-HSD, testicular antioxidant enzymes (catalase and superoxide dismutase) and low plasma level of testosterone were noted in diabetic rat in respect to the control. After oral administration of said fraction to diabetic rat, levels of above sensors were resettled toward the control. A significant decrease in the number of different generations of germ cells at the stage VII of spermatogenesis in diabetic rat was noted which were recovered significantly toward the control in the fraction-treated diabetic group. It was supported by the correction in gene expression of testicular Δ5, 3ß- HSD, 17ß- HSD, Bcl-2 and Bax in the fraction-treated diabetic group. Conclusions The threshold dose of ethyl-acetate fraction of methanolic extract of C. sinensis leaves is 100 mg/kg body weight for the recovery of testicular hypofunction in a diabetic rat model.

Antioxidant and hypoglycemic effects of Momordica cochinchinensis Spreng: (Gac) aril extract on reproductive damages in streptozotocin (STZ)-induced hyperglycemia mice / Efectos antioxidantes e hipoglucémicos del extracto de aril de Momordica cochinchinensis Spreng: (Gac) sobre los daños reproductivos en ratones con hiperglucemia inducida por streptozotocin (STZ)

The aim of present study was to investigate the effect of Momordica cochinchinensis (Gag) aril (GA) aqueous extract on male reproductive system of streptozotocin (STZ)-induced hyperglycemia (HG) mice. GA were extracted with distilled water (DW) and analyzed for in vitro antioxidant capacities. ICR male mice were divided into 7 groups: 1) control, 2) DW, 3) GA 1000 mg/kg BW, 4) HG, 5) HG + glibenclamide, 6 and 7) HG + GA 500 and 1000 mg/kg BW respectively (7 mice/ group). In HG groups, mice were induced by STZ at single dose (150 mg/kg BW). They were treated for consecutive 35 days. All groups were compared for blood glucose levels, weights and histopathologies of reproductive organs, sperm concentration including testicular tyrosine phosphorylation protein patterns by Immuno-Western blotting. The results showed that GA processed antioxidant activities and could significantly decrease blood glucose levels and increase sperm concentration in HG mice. Moreover, GA could change the density of a testicular 70 kDa protein in HG-GA groups. In conclusion, GA extract could improve hyperglycemia and male reproductive damages in STZ-induced HG mice.

El objetivo de este estudio fue investigar el efecto del extracto acuoso de Momordica cochinchinensis (Gag) aril (GA) en el sistema reproductor masculino de ratones hiperglucémicos inducidos por estreptozotocina (STZ). GA fue extraída con agua destilada (DW) y se analizaron las capacidades antioxidantes in vitro. Ratones ICR machos fueron divididos en 7 grupos: 1) control, 2) DW, 3) GA 1000 mg / kg PC, 4) HG, 5) HG + glibenclamida, 6 y 7) HG + GA 500 y 1000 mg / kg PC, respectivamente (7 ratones / grupo). En los grupos HG, los ratones fueron inducidos con STZ en dosis única (150 mg / kg BW). Fueron tratados durante 35 días consecutivos. En todos los grupos se compararon los niveles de glucosa en sangre, los pesos y las histopatologías de los órganos reproductores, la concentración de espermatozoides, incluídos los patrones testiculares de proteínas tirosina fosforilada por Inmuno-Western blot. Los resultados mostraron que GA procesaba actividades antioxidantes y podían disminuir significativamente los niveles de glucosa en sangre y aumentar la concentración de espermatozoides en ratones HG. Además, GA podría cambiar la densidad de una proteína testicular de 70 kDa en grupos HG-GA. En conclusión, el extracto de GA podría mejorar la hiperglucemia y los daños reproductivos masculinos inducidos por STZ en ratones HG.

Iridoid glycoside from Cornus officinalis ameliorated diabetes mellitus-induced testicular damage in male rats: Involvement of suppression of the AGEs/RAGE/p38 MAPK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis (CO) has been widely used as a traditional Chinese medicine for treating diabetes mellitus (DM) and its complications. Iridoid glycoside from C. officinalis (IGCO) can resist apoptosis, hyperglycemia, oxidation and so on. The aim of this study was to investigate the therapeutic effects of IGCO on DM-induced testicular damage through inhibition of the AGEs/RAGE/p38 MAPK signaling pathway. MATERIALS AND METHODS: A DM model of male Wistar rats was induced with streptozotocin injection (30mg/kg, i.p.) and high-fat diet. The DM rats were administrated with IGCO at low and high doses (15 and 30mg/kg, p.o.) for 12 weeks. Testicular damage was evaluated by estimating relative testicular weights, testicular pathohistology, sperm count, live sperm rate, endogenous sex hormone level and activity of testicular marker enzymes. Besides, general diabetic symptoms, renal function, oxidative stress parameters and testicular apoptosis marker were also determined. Finally, the mechanism was explored based on the AGEs/RAGE/p38 MAPK pathway. RESULTS: IGCO effectively mitigated the general symptoms of DM rats including weight loss, polydipsia, polyphagia, polyuria, elevated blood glucose level and low serum insulin level. Nourishing the kidney evidently, IGCO reduced serum creatinine, urea nitrogen and urine protein excretion, and also markedly protected against DM-induced testicular damage by increasing testis/body weight ratio and live sperm rate, improving the histomorphology of testes, upregulating testosterone, LH, FSH and GnRH levels and preventing the decrease of testicular marker enzymes LDH, ACP and γ-GT. Moreover, IGCO showed considerable anti-oxidative and anti-apoptotic effects, which downregulated the increase of ROS and MDA levels, restored SOD and CAT activities, and decreased spermatogenic cell apoptosis and Bax/Bcl-2 ratio. In the end, the increased AGEs, RAGE and p-p38 MAPK protein levels in DM rats were also reversed by IGCO significantly. CONCLUSIONS: The kidney tonic IGCO well protected DM rats from testicular damage, which may be related to suppression of the AGEs-RAGE-p38 MAPK pathway.

Thymoquinone supplementation ameliorates lead-induced testis function impairment in adult rats.

This study was realized to investigate the possible beneficial effect of thymoquinone (TQ), the major active component of volatile oil of Nigella sativa seeds, against lead (Pb)-induced inhibition of rat testicular functions. Adult rats were randomized into four groups: a control group receiving no treatment; a Pb group exposed to 2000 parts per million (ppm) of Pb acetate in drinking water; a Pb-TQ group co-treated with Pb (as in Pb group) plus TQ (5 mg/kg body weight (b.w.)/day, per orally (p.o.)); and a TQ group receiving TQ (5 mg/kg b.w./day, p.o.). All treatments were for 5 weeks. No significant differences were observed for the body weight gain or for relative testes weight among the four groups of animals. Testicular Pb content significantly increased in metal-intoxicated rats compared with that in control rats. TQ supplementation had no effect on this testicular Pb accumulation. Interestingly, when coadministrated with Pb, TQ significantly improved the low plasma testosterone level and the decreased epididymal sperm count caused by Pb. In conclusion, the results suggest, for the first time, that TQ protects against Pb-induced impairment of testicular steroidogenic and spermatogenic functions. This study will open new perspectives for the clinical use of TQ in Pb intoxication.