Attenuation of doxorubicin-induced hypothalamic-pituitary-testicular axis dysfunction by diphenyl diselenide involves suppression of hormonal deficits,oxido-inflammatory stress and caspase 3 activity in rats

BackgroundDoxorubicin (DOX) is one of the popular anti-cancer drugs in the world and several literatures have implicated it in various toxicities especially cardiotoxicity and reproductive toxicity. Diphenyl diselenide (DPDS) is well acknowledged for its compelling pharmacological effects in numerous disease models and chemically-mediated toxicity. This study was carried out to investigate the effect of DPDS on DOX-induced changes in the reproductive indices of male Wistar rats.MethodsRats were intraperitoneally injected with 7.5 mg/kg body weight of DOX alone once followed by treatment with DPDS at 5 and 10 mg/kg for seven successive days. Excised hypothalamus, testes and epididymis were processed for biochemical and histological analyses.ResultsDPDS treatment significantly (p < 0.05) abated DOX-induced oxidative damage by decreasing the levels of oxidative stress indices such as hydrogen peroxide, reactive oxygen and nitrogen species, and lipid peroxidation with a respective improvement in the level of glutathione in the hypothalamic, testicular and epididymal tissues of DOX-treated rats. The activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione S-transferase and glutathione peroxidase were upregulated in the DPDS co-treated group. DPDS co-treatment alleviates the burden of DOX-induced inflammation by significant reductions in myeloperoxidase activity, levels of nitric oxide and tumor necrosis factor alpha with concomitant decline in the activity of caspase-3, an apoptotic biomarker. Consequently, significant improvement in the spermiogram, levels of reproductive hormones (follicle stimulating hormone, luteinizing hormone, prolactin, serum testosterone and intra-testicular testosterone) levels in the DPDS co-treatment group in comparison to DOX alone-treated group were observed. Histology results of the testes and epididymis showed that DPDS significantly alleviated pathological lesions induced by DOX in the animals.ConclusionDPDS may modulate reproductive toxicity associated with DOX therapy in male cancer patients.     

A study on the potential reprotoxic effects of thimerosal in male albino rats

Thimerosal is ethyl mercury based compound which is being used as a preservative in vaccines since decades. Pharmaceutical products and vaccines that contain thimerosal are among the potential source of mercury exposure. Current research was intended to ascertain the reprotoxic effects of thimerosal on rat testes. Twenty-four adult male albino rats were sorted into four groups (n = 6). The first group was a control group. Rats of experimental Group 2, 3 and 4 were treated with various dosages of thimerosal (0.5, 10, 50 mg/kg) respectively. Rats were decapitated after thirty days of trial and different parameters were analyzed. Thimerosal exposure resulted in a significant decrease in antioxidant enzyme activities including catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione reductase (GSR) and increased levels of thiobarbituric acid reactive substances (TBARS). Different doses of thimerosal significantly decreased (p < 0.05) the concentration of plasma testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH). Additionally, Daily sperm production (DSP) and efficiency of daily sperm production were significantly reduced followed by thimerosal exposure. Moreover, thimerosal significantly (p < 0.05) decreased the primary spermatocytes, secondary spermatocytes, number of spermatogonia along with spermatids. Thimerosal induced adverse histopathological and morphological changes in testicular tissues such as decreased Leydig cells, diameter of seminiferous tubules, tunica albuginea height and epithelial height. On the other hand, the increase in tubular lumen and interstitial spaces was observed due to thimerosal. These outcomes indicated that thimerosal has potential reprotoxic effects in male albino rats.     

Tangeretin ameliorates bisphenol induced hepatocyte injury by inhibiting inflammation and oxidative stress

Bisphenol A (BPA) is an industrial toxicant that can potentially damage the liver. Tangeretin (TGN) is a natural flavonoid that displays various pharmacological activities. This experiment was carried out to evaluate the protective effects of TGN against BPA-induced hepatic impairment in the male albino rat. Twenty-four male albino rats were equally divided into four different groups: control, BPA (100 mg/kg), BPA + TGN (100 mg/kg + 50 mg/kg) and TGN (50 mg/kg). BPA exposure significantly decreased the activities of catalase (CAT), superoxidase dismutase (SOD), peroxidase (POD), glutathione reductase (GSR), glutathione S-transferase (GST), and glutathione (GSH) content while substantially increasing the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H₂O₂) levels. A substantial increase in the levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) was also observed in BPA treated rats. Moreover, BPA significantly increased the inflammatory markers, including tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB), Interleukin-6 (IL-6), Interleukin-1β (IL-1β)levels, cyclooxygenase-2 (COX-2) activity, and histopathological damages. However, co-treatment with TGN efficiently minimized the BPA-induced biochemical, inflammatory, and histopathological impairments in rat liver. The present study shows that TNG has significant potential to avert BPA-induced liver damage to its antioxidant and anti-inflammatory properties.     

Role of soy isoflavone in preventing aging changes in rat testis: Biochemical and histological studies

Testicular function and structure harmed by ageing. Goal of this research was to assess preventive actions of soy isoflavone oral administration for 8 weeks on testes of old male albino rats, and potential mechanisms of action. Adult control (N = 10) and elderly control (N = 10) rats were fed usual diet, while aged treatment group (N = 10) gave oral 100 mg/kg soy isoflavone daily for 8 weeks. ELISA kits were used to measure testosterone levels and oxidative stress indicators [malonaldehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD)] in serum. Aging produced functional and structural testicular changes and decreased ki67 proliferative marker immunoexpression versus adult control rats due to enhancement of oxidative stress. Soy isoflavone exerted protective effect on testicular function and structure as assessed by increase serum levels of testosterone and preserved histological structure and immune-expression features. These protected effects due to isoflavone antioxidant properties proved by decrease in serum values of MDA, while GSH and SOD were elevated after treatment. These data demonstrated protective effects of isoflavone against age changes in rat testes, by reducing oxidative stress and increasing antioxidants and testicular ki67 proliferative marker immunoexpression.     

Forskolin ameliorates mancozeb‐induced testicular and epididymal toxicity in Wistar rats by reducing oxidative toxicity and by stimulating steroidogenesis

In the present study, we have tested the beneficial effects of forskolin in protecting the mancozeb‐induced reproductive toxicity in rats. Adult male Wistar rats were exposed to either mancozeb (500 mg/kg body weight/day) or forskolin (5 mg/kg body weight/day) or both for 65 days and analyzed for spermatogenesis and steroidogenesis and testicular and epididymal oxidative toxicity. A significant decrease in daily sperm production, epididymal sperm count, motile, viable, and hypo‐osmotic swelling‐tail swelled sperm was observed in mancozeb‐treated rats. The activity levels of testicular 3β‐hydroxysteroid dehydrogenase and 17β‐hydroxysteroid dehydrogenase and circulatory testosterone levels were significantly decreased in mancozeb‐treated rats. Exposure to mancozeb resulted in a significant decrease in glutathione levels and superoxide dismutase and catalase activity levels with an increase in lipid peroxidation levels in the testes and epididymis. Coadministration of forskolin mitigated the mancozeb‐induced oxidative toxicity and suppressed steroidogenesis and spermatogenesis.     

4-Vinylcyclohexene diepoxide disrupts sperm characteristics,endocrine balance and redox status in testes and epididymis of rats

Objectives: Exposure to 4-vinylcyclohexene diepoxide (VCD) was reported to induce testicular germ cell toxicity in rodents. However, there is paucity of information on the precise biochemical and molecular mechanisms of VCD-induced male reproductive toxicity.

Methodology: This study investigated the influence of VCD on testicular and epidydimal functions following oral exposure of Wistar rats to VCD at 0, 100, 250 and 500?mg/kg for 28 consecutive days.

Results: Administration of VCD significantly decreased the body weight gain and organo-somatic indices of the testes and epididymis. When compared with the control, VCD significantly decreased superoxide dismutase and catalase activities in the testes whereas it significantly decreased superoxide dismutase activity but increased catalase activity in the epididymis. Moreover, while glutathione peroxidase activity and glutathione level remain unaffected, exposure of rats to VCD significantly increased glutathione S-transferase activity as well as hydrogen peroxide and malondialdehyde levels in testes and epididymis of the treated rats. The spermiogram of VCD-treated rats showed significant decrease in epididymal sperm count, sperm progressive motility, testicular sperm number and daily sperm production when compared with the control. Administration of VCD significantly decreased circulatory concentrations of follicle-stimulating hormone, luteinizing hormone and testosterone along with testicular and epididymal degeneration in the treated rats. Immunohistochemical analysis showed significantly increased cyclooxygenase-2, inducible nitric oxide synthase, caspase-9 and caspase-3 protein expressions in the testes of VCD-treated rats.

Conclusion: Exposure to VCD induces testicular and epidydimal dysfunctions via endocrine suppression, disruption of antioxidant enzymes activities, increase in biomarkers of oxidative stress, inflammation and apoptosis in rats.     

Testicular toxicity induced by dietary cadmium in cocks and ameliorative effect by selenium

Cadmium (Cd) is an ubiquitous environmental pollutant that has been associated with male reproductive toxicity in animal models. However, little is known about the reproductive toxicity of Cd in birds. To investigate the toxicity of Cd on male reproduction in birds and the protective effects of selenium (Se) against subchronic exposure to dietary Cd, 100-day-old cocks received either Se (as 10 mg Na₂SeO₃ per kg of diet), Cd (as 150 mg CdCl₂ per kg of diet) or Cd + Se in their diets for 60 days. Histological and ultrastructural changes in the testis, the concentrations of Cd and Se, amount of lipid peroxidation (LPO), the activities of the antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPx), and apoptosis and serum testosterone levels were determined. Exposure to Cd significantly lowered SOD and GPx activity, Se content in the testicular tissue, and serum testosterone levels. It increased the amount of LPO, the numbers of apoptotic cells and Cd concentration and caused obvious histopathological changes in the testes. Concurrent treatment with Se reduced the Cd-induced histopathological changes in the testis, oxidative stress, endocrine disorder and apoptosis, suggesting that the toxic effects of cadmium on the testes is ameliorated by Se. Se supplementation also modified the distribution of Cd in the testis.     

Improvement of Mercuric Chloride-Induced Testis Injuries and Sperm Quality Deteriorations by Spirulina platensis in Rats

The present study was undertaken to investigate the protective effect of the filamentous cyanobacterium Spirulina platensis (S. platensis) on mercury (II) chloride (HgCl₂)-induced oxidative damages and histopathological alterations in the testis of Wistar albino rats. The animals were divided into four equal groups, i ) control, ii ) HgCl₂, iii ) S. platensis and iv ) combination of HgCl₂+S. platensis. Oxidative stress, induced by a single dose of HgCl₂ (5 mg/kg, bw; subcutaneously, s.c.), substantially decreased (P<0.01) the activity level of testicular key enzymatic antioxidant biomarkers (superoxide dismutase, SOD; catalase, CAT and glutathione peroxidase, GPx), oxidative stress makers (blood hydroperoxide; testicular reduced glutathione, GSH and malondialdehyde, MDA), and testicular mercury levels. Moreover, HgCl₂ administration resulted in a significant (P<0.01) increase in the number of sperms with abnormal morphology and decrease in epididymal sperm count, motility, plasma testosterone level and testicular cholesterol. Furthermore, HgCl₂ exposure induced histopathological changes to the testis including morphological alterations of the seminiferous tubules, and degeneration and dissociation of spermatogenic cells. Notably, oral pretreatment of animals with Spirulina (300 mg/kg, bw) lowered the extent of the observed HgCl₂-mediated toxicity, whereby significantly reducing the resulting lipid peroxidation products, mercury accumulation in the testis, histopathological changes of the testes and spermatozoal abnormalities. In parallel, the pretreatment with Spirulina also completely reverted the observed Hg-Cl₂-induced inhibition in enzymatic activities of antioxidant biomarkers (SOD, CAT and GPx) back to control levels. The pretreatment of rats with S. platensis significantly recovered the observed HgCl₂-mediated decrease in the weight of accessory sex organs. Taken together, our findings clearly highlight the role of S. platensis as a protective modulator of HgCl₂-induced testicular injuries and suggest some therapeutic potential in mammals. Further investigation of therapeutic strategies employing Spirulina against heavy metals toxicity in humans is therefore warranted.     

Male reproductive effect of nickel sulphate in mice

Nickel sulphate was administered orally to adult male mice at dose level of 5 and 10 mg/kg body weight (5 days per week) for 35 days. There was no change in body weight. However a significant decrease in absolute and organ-to-body weight ratios of testes, epididymides, seminal vesicles and prostate gland was observed. The sperm abnormality, associated with decrease in sperm motility and sperm count was also observed. Significant alterations in the activities of marker testicular enzymes, viz. sorbitol dehydrogenase (decreases), lactate dehydrogenase (increases) and -glutamyl transpeptidase (increases) associated with histopathological changes in testes, epididymides and seminal vesicles, were also observed. Accumulation of nickel in testes, epididymides and seminal vesicles was also observed. The study reveals that the oral exposure to nickel may affect the histology of testes, epididymides, seminal vesicles and sperms morphology. These testicular and spermatotoxic changes may be responsible for observed male mediated developmental toxic effects.     

Ameliorative effects of Anchomanes difformis aqueous extract against oxidative stress in the testes and epididymis of streptozotocin-induced diabetic male Wistar rats

Hyperglycemia is a central trait of diabetes mellitus (DM) and is linked to an increase in free radical generation and oxidative stress in the testes, resulting in testicular tissue damage and male infertility. Synthetic medicines are commonly used to manage diabetes; however, they are costly and associated with adverse effects. As a result, the search for a safer and affordable alternative from medicinal plants that contain antioxidants has become imperative to scavenge free radicals caused by hyperglycaemia, thereby alleviating male reproductive dysfunction. Therefore, the present aimed to investigate the ameliorative effects of Anchomanes difformis aqueous extract against oxidative stress in the testes and epididymis of streptozotocin-induced diabetic male Wistar rats. A total of 64 male Wistar rats (eight weeks old) weighing 180 ± 10 mg/kg were divided into seven groups at random. Type 2 diabetic mellitus (T2DM) was induced by streptozotocin (STZ) and a 10% fructose injection intraperitoneally using 40 mg/kg body weight rats. The levels of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) activity, reduced glutathione (GSH) concentration, and ferric reducing antioxidant (FRAP) as well as 2, 2-diphenyl-1-picrylhydrazyl (DPPH) values were used to establish the testicular oxidative status. It was found that A. difformis extract significantly (p < 0.05) lowered MDA levels in diabetic rats. Both CAT and SOD activity were significantly (p < 0.05) lower following induction of DM and increased (p < 0.05) after treating with A. difformis. The findings of this study show that A. difformis extract could be a promising source of lead compounds for the development of a therapeutic agent to treat male infertility caused by DM complications.     

Ameliorating effects of agomelatine on testicular and epididymal damage induced by methotrexate in rats

The aim of this study was to investigate the possible prophylactic effects of agomelatine (AGO) against testicular and epididymal damage induced by methotrexate (MTX) in rats. Twenty‐four male Wistar albino rats were divided into three groups: Group I (control group), Group II (MTX group: 20 mg/kg MTX, i.p, single dose), and Group III (MTX+AGO group: 20 mg/kg MTX, i.p, single dose+40 mg/kg AGO; gavage, 7 days). The rats were killed under anesthesia 24 hours after the last AGO application. Testicular and epididymal tissues were bilaterally removed for morphometric, biochemical, pathological, and immunohistochemical analyses. Body, testicular, and epididymal weights were measured. Malondialdehyde (MDA), superoxide dismutase, catalase, and glutathione peroxidase levels were measured in testes. Sperm count, hyperemia, edema, inflammatory reaction, degenerated and necrotic cells were evaluated by histopathological analysis. In addition, inducible nitric oxide synthase (iNOS), granulocyte colony‐stimulating factor (G‐CSF), osteopontin (OPN), and heat shock protein‐70 (HSP70) immune reactions were analyzed in testes and epididymides. Decreased epididymal weights, increased MDA levels, decreased sperm count, hyperemia, edema, inflammatory reaction, and degenerated and necrotic cells were observed in the MTX group. In addition, iNOS, HSP70, G‐CSF, and OPN immune reactions were increased. AGO improved morphometric, biochemical, histopathological, and immunohistochemical findings. The present study confirms that MTX induces testicular and epididymal damage both biochemically and immunohistochemically. However, AGO demonstrated ameliorative effects on both biochemical and pathological findings of the current study.     

Ginkgo biloba supplement abates lead-induced endothelial and testicular dysfunction in Wistar rats via up-regulation of Bcl-2 protein expression,pituitary-testicular hormones and down-regulation of oxido-inflammatory reactions

BackgroundApoptotic and oxido-inflammatory pathways have been found to be up-regulated in lead acetate poisoning which has been associated to endothelial and testicular dysfunctions. It is yet uncertain, nevertheless, if treatment with Ginkgo biloba supplements (GBS), a flavonoid-rich natural product can lessen the adverse effects of lead on endothelial and testicular functions. This study investigated the impact of Ginkgo biloba supplementation on lead-induced endothelial and testicular dysfunctions.MethodsThe animals were treated with GBS (50 mg/kg and 100 mg/kg orally) for 14 days following oral exposure to lead acetate (25 mg/kg) for 14 days. After euthanasia, blood samples, epididymal sperm, testes, and aorta were collected. The quantities of the hormones (testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH), as well as the anti-apoptotic, oxidative, nitrergic, inflammatory markers, were then determined using immunohistochemistry, ELISA, and conventional biochemical methods.ResultsGBS reduced lead-induced oxidative stress by increasing the levels of the antioxidant enzymes catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD), while lowering malondialdehyde (MDA) in endothelium and testicular cells. Normal testicular weight was restored by GBS which also decreased endothelial endothelin-I and increased nitrite levels. TNF-α and IL-6 were decreased while Bcl-2 protein expression was enhanced. Lead-induced alterations in reproductive hormones (FSH, LH, and testosterone) were also restored to normal.ConclusionAccording to our result, using Ginkgo biloba supplement prevented lead from causing endothelial and testicular dysfunction by raising pituitary-testicular hormone levels, boosting Bcl-2 protein expression and lowering oxidative and inflammatory stress in the endothelium and testes.     

己烯雌酚对成年雄性金色中仓鼠的生殖毒性与氧化损伤的关系

为研究环境雌激素己烯雌酚(DES)的生殖毒性与活性氧(ROS)的关系,连续7天给成年金色中仓鼠皮下注射0、0.01、0.1、1mg/kgBWDES,称量睾丸重量、计算睾丸相对重量,光镜观察睾丸组织结构的变化,分光光度法检测睾丸组织和血浆中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、总抗氧化能力(T-AOC)和丙二醛(MDA)的含量。结果表明:1mg/kgBWDES导致睾丸萎缩、重量下降,曲细精管中生精细胞排列紊乱,管腔内几乎没有成熟精子;随着DES剂量的增加,睾丸组织中SOD、GSH-Px和T-AOC含量显著下降,MDA显著上升。提示DES的生殖毒性与ROS密切相关,DES通过降低抗氧化酶水平,增加ROS含量,干扰生精细胞正常功能,导致细胞死亡,表明氧化损伤可能是环境雌激素生殖毒性的作用机理之一。     

The effect of ghrelin pretreatment on epididymal sperm quality and tissue antioxidant enzyme activities after testicular ischemia/reperfusion in rats

Ghrelin, the endogenous ligand for growth hormone secretagogue receptor, has been reported to prevent ischemia/reperfusion (I/R) injury in various tissues by its antioxidant activity. Therefore, this study was aimed to investigate the effect of ghrelin on sperm quality and antioxidant enzyme activity in a rat testicular ischemia/reperfusion injury model. Forty-two male Wistar rats were divided into groups control, I/R, and I/R plus ghrelin. The right testes were rotated 720° for 1 h and were allowed to reperfuse for 4 h and 30 days thereafter. Ghrelin (40 nmol/kg IP) or vehicle (physiological saline) was administrated 15 min before reperfusion. After 4 h of reperfusion, a right orchiectomy was performed to measure the biochemical parameters. In addition, the sperm was collected from the epididymis after 30 days of reperfusion, and sperm characteristics were examined. The malondialdehyde levels of the testis tissues were significantly increased, but a statistically significant decrease was found in the superoxide dismutase, glutathione peroxidase, and catalase activities in the I/R group as compared with the control, indicating I/R injury. The sperm evaluation showed a significant reduction in all characteristics resulted from I/R compared with the control. In the ghrelin-treated group, the malondialdehyde values were significantly lowered, and only enzyme activity of glutathione peroxidase showed significant increases compared with the I/R group. Ghrelin significantly enhanced sperm motility, movement, and concentration but did not prevent I/R-induced reduction in membrane integrity in the testes of rats compared to the I/R group. Our results suggest that ghrelin treatment has a protective role on IR-induced testicular injury, and this effect may be due to its antioxidant properties.     

Effect of Filgrastim on adult male rats’ fertility and reproductive performance

Filgrastim is a recombinant protein used in treatment neutropenia caused by myelosuppressive medications for patients with non-myeloid cancer. However, its effect in male fertility is not clear. So, the current work aims to clarify the effect of Filgrastim on the reproductive state in Wistar rats. Eighteen (18) male Wistar rats were divided into three groups (6/each). Group (I) where the rats were injected with 0.5 ml/kg/day of distilled water and served as Control Group. The Group (II) animals received intraperitoneal injection of therapeutic dose of 30.83 mcg/kg/day of Filgrastim for one week. The Group (III) rats received the same dose by the same route of Filgrastim for two weeks. Sera of blood samples were processed for serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TS). Semen analysis and resazurine reduction test (RRT) were performed. Assaying for malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) was done. The testes were retrieved for histopathological and immunohistochemical studies for caspase-3 detection. Our results revealed that filgrastim affects sperm morphology, significantly decreased the RRT and the reproductive hormones level, elevated the oxidative stress status and induced several histopathological changes in testes with an increased in immunoexpression of caspase-3 in testes tissues. The results of this work demonstrated that Filgrastim may had a deleterious effect on male fertility.     

Lycopene is superior to moringa in improving fertility markers in diet-induced obesity male rats

Obesity is a condition of chronic tissue inflammation and oxidative stress that poses as a risk factor for male infertility. Moringa oleifera oil extract is known to have cholesterol-lowering properties and a potential to treat obesity, while lycopene is a potent antioxidant. We hypothesize that Moringa or lycopene may improve male fertility markers in an animal model of diet-induced obesity. Male Albino rats (n = 60) were randomized to receive regular chow (RC) or high-fat diet (HFD) for 12 weeks (n = 30 each). Animals in each arm were further randomized to receive gavage treatment with corn oil (vehicle), lycopene (10 mg/kg), or Moringa (400 mg/kg) for four weeks starting on week 9 (n = 10 each). Animals were sacrificed at 12 weeks, and blood was collected to assess lipid profile, serum testosterone, and gonadotropin levels. The testes and epididymides were removed for sperm analysis, oxidative stress and inflammatory markers, and histopathological assessment. In comparison to their RC littermates, animals on HFD showed an increase in body weights, serum lipids, testosterone and gonadotrophin levels, testicular oxidative stress and inflammatory markers, as well as sperm abnormalities and disrupted testicular histology. Moringa or lycopene reduced body weight, improved oxidative stress, and male fertility markers in HFD-fed animals with lycopene exhibiting better anti-antioxidant and anti-lipidemic effects. Lycopene is superior to Moringa in improving male fertility parameters, possibly by attenuating oxidative stress.     

Ellagic acid and rosmarinic acid attenuate doxorubicin‐induced testicular injury in rats

The anticancer drug doxorubicin causes testicular toxicity as an undesirable effect. The present study was undertaken to investigate the possible protection of ellagic acid and rosmarinic acid during doxorubicin administration. For this purpose eight groups of male Sprague–Dawley rats were used (n = 10), one group received vehicle served as control, and other groups received 5 mg/kg doxorubicin twice a week for 2 weeks for a cumulative dose of 20 mg/kg, ellagic acid (10 mg/kg/day, 14 consecutive days p.o.), rosmarinic acid (75 mg/kg/day, 14 consecutive days p.o.), ellagic acid and rosmarinic acid. The latter three regimens were given to control and doxorubicin‐received rats. Doxorubicin decreased testicular relative weight, sperm count, motility, serum testosterone, testicular glycogen, and sialic acid with increased incidence of histopathological changes, oxidative stress, tumor necrosis factor‐alpha, as well as cholinesterase activity. Conversely, ellagic and rosmarinic acid treatment ameliorated such damage, thus showing the possibility to use as an adjuvant during doxorubicin treatment.     

Effect of Physalis peruviana L. on Cadmium-Induced Testicular Toxicity in Rats

Cadmium (Cd) stimulates the production of reactive oxygen species and causes tissue damage. We investigated here the protective effect of Physalis peruviana L. (family Solanaceae) against cadmium-induced testes toxicity in rats. Twenty-eight Wistar albino rats were used. They were divided into four groups (n?=?7). Group 1 was used as control. Group 2 was intraperitoneally injected with 6.5 mg/kg body weight (bwt) of cadmium chloride for 5 days. Group 3 was orally treated with 200 mg/kg bwt of methanolic extract of physalis (MEPh). Group 4 was pretreated with MEPh before cadmium for 5 days. Changes in body and testes weights were determined. Oxidative stress markers, antioxidant enzymes, and testosterone level were measured. Histopathological changes of testes were examined, and the immunohistochemical staining for the proapoptotic (caspase-3) protein was performed. The injection of cadmium caused a significant decrease in body weight, while a significant increase in testes weight and testes weight index was observed. Pretreatment with MEPh was associated with significant reduction in the toxic effects of Cd as shown by reduced testicular levels of malondialdehyde, nitric oxide, and caspase-3 expression and increased glutathione content, and the activities of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and testosterone were also increased. Testicular histopathology showed that Cd produced an extensive germ cell apoptosis, and the pretreatment of MEPh in Cd-treated rats significantly reduced Cd-induced testicular damage. On the basis of the above results, it can be hypothesized that P. peruviana L. has a protective effect against cadmium-induced testicular oxidative stress and apoptosis in the rat.     

Neural network assessment of herbal protection against chemotherapeutic-induced reproductive toxicity

The aim of this study is to assess the protective effects of Ginkgo biloba's (GB) extract against chemotherapeutic-induced reproductive toxicity using a data mining tool, namely Neural Network Clustering (NNC) on two types of data: biochemical & fertility indicators and Texture Analysis (TA) parameters. GB extract (1 g/kg/day) was given orally to male albino rats for 26 days. This period began 21 days before a single cisplatin (CIS) intraperitoneal injection (10 mg/kg body weight). GB given orally significantly restored reproductive function. Tested extract also notably reduced the CIS-induced reproductive toxicity, as evidenced by restoring normal morphology of testes. In GB, the attenuation of CIS-induced damage was associated with less apoptotic cell death both in the testicular tissue and in the sperms. CIS-induced alterations of testicular lipid peroxidation were markedly improved by the examined plant extract. NNC has been used for classifying animal groups based on the quantified biochemical & fertility indicators and microscopic image texture parameters extracted by TA. NNC showed the separation of two clusters and the distribution of groups among them in a way that signifies the dose-dependent protective effect of GB. The present study introduces the neural network as a powerful tool to assess both biochemical and histopathological data. We also show here that herbal protection against CIS-induced reproductive toxicity utilizing classic methodologies is validated using neural network analysis.