6‐Gingerol‐rich fraction prevents disruption of histomorphometry and marker enzymes of testicular function in carbendazim‐treated rats

Previous investigations demonstrated that 6‐gingerol‐rich fraction (6‐GRF) prevented testicular toxicity via inhibition of oxidative stress and endocrine disruption in CBZ‐treated rats. The influence of 6‐GRF on alterations in histomorphometry and marker enzymes of testicular function in CBZ‐treated rats which hitherto has not been reported was investigated in this study. The animals were orally administered either CBZ (50 mg/kg) alone or in combination with 6‐GRF (50, 100 and 200 mg/kg) for 14 consecutive days. Histomorphormetric analysis demonstrated that 6‐GRF significantly prevented CBZ‐mediated increase in the organo‐somatic index of the testes and seminiferous tubular diameter as well as the reduction in epithelium height and tubular length of testes in the rats. Similarly, 6‐GRF ameliorated CBZ‐induced disruption in the epithelium height as well as in the proportion of tubule and interstitium of the epididymis the treated rats. Furthermore, 6‐GRF prevented CBZ‐mediated increase in testicular acid phosphatase activity and the decrease in testicular alkaline phosphatase, aminotransferases, glucose‐6‐phosphate dehydrogenase and lactate dehydrogenase activities. Moreover, 6‐GRF ameliorated CBZ‐induced reduction in the testicular and epididymal sperm count and sperm motility in the treated rats. Conclusively, 6‐GRF enhances key functional enzymes involve in spermatogenesis and maintains histo‐architecture of testes and epididymis in CBZ‐treated rats.     

Gallic acid protects against cyclophosphamide‐induced toxicity in testis and epididymis of rats

The protective role of gallic acid (GA) on reproductive toxicity induced by cyclophosphamide (CPA), an antineoplastic drug, was investigated in male Wistar rats. Sixty rats were grouped into 10 rats per group. Group 1 (control) received distilled water. Rats in groups 2 and 3 received GA alone at 60 and 120 mg kg^?1 for 14 consecutive days, respectively. Group 4 received a single intraperitoneal dose of CPA at 200 mg kg^?1 on day 1. Groups 5 and 6 received a single dose of CPA (200 mg kg^?1) intraperitoneally on day 1 followed by treatment with GA at 60 and 120 mg kg^?1 for 14 consecutive days, respectively. In testes and epididymis of the treated rats, CPA administration resulted in significant elevation (P < 0.05) in malondialdehyde (MDA), nitrite and hydrogen peroxide levels. There was a significant decrease in the activities of superoxide dismutase and glutathione‐S‐transferase. Furthermore, there were significant reductions in plasma luteinising hormone (LH), follicle stimulation hormone (FSH) and testosterone levels, which were accompanied by significant decrease in sperm motility and viability in CPA‐treated rats. Histological examination revealed marked testicular and epididymal atrophy in CPA alone treated rats and these aberrations were reversed by GA. In conclusion, GA has capacity to protect against reproductive toxicity induced by cyclophosphamide.     

Testosterone influences the expression and distribution of the cation‐dependent mannose‐6‐phosphate receptor in rat epididymis. Implications in the distribution of enzymes

The mammalian epididymis plays a role in sperm maturation through its secretory activity. Among the proteins secreted by the epithelium, there are significant amounts of acid hydrolases. In most cell types, the normal distribution of lysosomal enzymes is mediated by mannose‐6‐phosphate receptors (MPRs). In this study, we analysed the expression and distribution of the cation‐dependent MPR (CD‐MPR) in epididymis from control, castrated or castrated rats with testosterone replacement. It was observed that expression of CD‐MPR increased due to castration in all regions of the epididymis, which was reversed by injection of testosterone. We also measured the activity of α‐mannosidase and observed that the castration tends to increase the retention of this enzyme in the tissue, which is reversed by the hormone replacement. In corpus, this resulted in a reduced secretion of the enzyme. Immunohistochemistry showed that CD‐MPR has a supranuclear location (different from the cation‐independent MPR), most likely in principal cells, and low reactivity in other cell types. The signal in castrated animals was more intense and tended to redistribute towards the apical cytoplasm. Thus, we concluded that expression and distribution of CD‐MPR is affected by decrease of testosterone in rat epididymis, and this could change the distribution of lysosomal enzymes.     

Protective effect of Gallic acid on doxorubicin‐induced testicular and epididymal toxicity

The effect of Gallic acid (GA) on doxorubicin (DOX)‐induced testicular and epididymal toxicity was investigated in experimental rat model. The rats were randomly divided into six groups of 10 animals per group. Rats in group A received clean tap water ad libitum. Rats in group B were administered DOX intraperitoneally at 15 mg/kg on the eighth day of the experiment. Animals in groups C and D received 60 and 120 mg/kg GA orally for 7 days with 15 mg/kg DOX on the eighth day. Rats in groups E and F received 60 and 120 mg/kg GA alone orally for 7 days. The animals were sacrificed 24 hr after the last administration. DOX administration led to a significant (p < 0.05) increase in hydrogen peroxide and malondialdehyde levels with significant reduction in antioxidant enzymes and reduced glutathione levels. DOX administration also led to a significant increase in total sperm abnormalities and prolactin together with a significant decrease in testosterone levels. Immunohistochemistry revealed higher expressions of caspase 3 in the testicular tissues of rats that received DOX alone. Together, pre‐treatment with GA attenuated markers of oxidative stress, reversed sperm abnormality and ameliorated the observed aberration in plasma testosterone and prolactin levels.     

Melatonin prevents gentamicin‐induced testicular toxicity and oxidative stress in rats

This study investigated the protective effects of melatonin (MT) against gentamicin (GM)‐induced testicular toxicity and oxidative damage in rats. GM (100 mg kg^?1) was injected intraperitoneally (i.p.) to rats for 6 days. MT (15 mg kg^?1) was administered i.p. to rats for 6 days at 1 hr after the GM treatment. GM caused a decrease in prostate and seminal vesicle weights, sperm count and sperm motility. Histopathological examination showed various morphological alterations in the testis, characterised by degeneration of spermatogonia/spermatocytes, decrease in the number of early spermatogenic cells and vacuolisation. In addition, an increased malondialdehyde concentration and decreased glutathione content and glutathione reductase, catalase and glutathione‐S‐transferase activities were found in the testis. In contrast, MT treatment significantly attenuated the testicular toxicity of GM, including decreased reproductive organ weights, sperm count, and sperm motility and increased histopathological alterations. MT also had an antioxidant benefit by decreasing the lipid peroxidative product malondialdehyde and increasing the level of the antioxidant glutathione and the activities of antioxidant enzymes in the testis. These results indicate that MT prevents testicular toxicity induced by GM in rats, presumably due to its potent antioxidant activity, and its ability to inhibit lipid peroxidation, and restore antioxidant enzyme activity.     

The protective effect of vitamin E against oxidative damage caused by formaldehyde in the testes of adult rats

Aim:To investigate the effect of formaldehyde(FA)on testes and the protective effect of vitamin E(VE)againstoxidative damage by FA in the testes of adult rats.Methods:Thirty rats were randomly divided into three groups:(1)control;(2)FA treatment group(FAt);and(3)FAt VE group.FAt and FAt VE groups were exposed to FA byinhalation at a concentration of 10 mg/m~3 for 2 weeks.In addition,FAt VE group were orally administered VE duringthe 2-week FA treatment.After the treatment,the histopathological and biochemical changes in testes,as well as thequantity and quality of sperm,were observed.Results:The testicular weight,the quantity and quality of sperm,theactivities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and glutathione(GSH)were significantlydecreased whereas the level of malondialdehyde(MDA)was significantly increased in testes of rats in FAt groupcompared with those in the control group.VE treatment restored these parameters in FAt VE group.In addition,microscopy with hematoxylin-eosin(HE)staining showed that seminiferous tubules atrophied,seminiferous epithelialcells disintegrated and shed in rats in FAt group and VE treatment significantly improved the testicular structure in FAt VE group.Conclusion:FA destroys the testicular structure and function in adult rats by inducing oxidative stress,and this damage could be partially reversed by VE.(Asian J Androl 2006 Sep;8:584-588)     

Melatonin abrogates nonylphenol‐induced testicular dysfunction in Wistar rats

Endocrine‐disrupting chemicals present in the environment can bring about hormonal imbalance and be potentially harmful to the human health. Alkylphenols are omnipresent in the environment as they are constituents of several products. The aim of this study was to evaluate the effect of exogenous melatonin treatment on nonylphenol (NP)‐induced oxidative stress and testicular toxicity in Wistar rats using biochemical and histopathological parameters. The oxidative stress biomarkers, activities of enzymatic and non‐enzymatic antioxidants and histopathological evaluation were performed in testicular tissues. NP caused elevated TBARS levels and marked alteration of both nonenzymatic and enzymatic biomarkers. Furthermore, severe histopathological alterations were observed in the testis of NP‐exposed animals as compared with that of the control rats. Melatonin supplementation ameliorated the alterations in these biochemical and histopathological variables in rats. In conclusion, our results demonstrated that melatonin through its antioxidant activity effectively protected against the NP‐induced testicular toxicity.     

Protective effect of alpha glucosyl hesperidin (G‐hesperidin) on chronic vanadium induced testicular toxicity and sperm nuclear DNA damage in male Sprague Dawley rats

The study was conducted to evaluate the vanadium‐induced testicular toxicity and its effect on sperm parameters, sperm nuclear DNA damage and histological alterations in Sprague Dawley rats and to assess the protective effect of G‐hesperidin against this damage. Treatment of rats with vanadium at a dose of 1 mg kg bw^?1 for 90 days resulted in significant reduction in serum testosterone levels, sperm count and motility. Further, a parallel increase in abnormal sperm morphology and adverse histopathological changes in testis was also associated with vanadium administration when compared to normal control. Moreover, sperm chromatin dispersion assay revealed that vanadium induces sperm nuclear DNA fragmentation. A marked increase in testicular malondialdehyde levels and decreased activity of antioxidant enzymes such as superoxide dismutase and catalase indicates vanadium‐induced oxidative stress. Co‐administration of G‐hesperidin at a dose of 25 and 50 mg kg bw^?1 significantly attenuated the sperm parameters and histological changes by restoring the antioxidant levels in rat testis. These results suggested that vanadium exposure caused reduced bioavailability of androgens to the tissue and increased free radical formation, thereby causing structural and functional changes in spermatozoa. G‐hesperidin exhibited antioxidant effect by protecting the rat testis against vanadium‐induced oxidative damage, further ensures antioxidant potential of bioflavonoids.     

The protective effect of esculetin against aluminium chloride-induced reproductive toxicity in rats

One of the prominent health problems caused by Aluminium was the decrease in male fertility rates. In the study, the protective effect of Esculetin (ESC) against the reproductive toxicity induced by Aluminium chloride (AlCl₃) was investigated. For this purpose, AlCl₃ was administrated to Wistar Albino rats at a dose of 34 mg/kg and ESC was administrated at a dose of 50 mg/kg for 70 days. It was determined that AlCl₃ treatment reduced sperm motility and concentration, increased dead/live rate and abnormal sperm rate. It decreased serum testosterone level, and co-treatment of ESC significantly regulated these values. In the AlCl₃-treated group, MDA level increased and GSH level, GPx and CAT activities decreased compared with those of the control group. However, co-treatment of ESC showed an amelioratory effect on the values except for CAT activity. It was observed that the expression level of NRF-2 increased in the ESC and AlCl₃ + ESC groups, and NF-κB increased in the AlCl₃ group with the control group. It was determined that Caspase-3 expression decreased, and Bcl-2 expression increased in AlCl₃ + ESC group compared to AlCl₃ group. It was also determined that AlCl₃-induced tissue injury was significantly prevented by ESC co-treatment.     

Therapeutic effect of ozone and rutin on adriamycin‐induced testicular toxicity in an experimental rat model

To evaluate the cytoprotective effects of rutin, ozone and their combination on adriamycin (ADR)‐induced testicular toxicity, 50 male albino rats were classified into five groups of ten animals each as follows: placebo group; ADR group; ADR + rutin group; ADR + ozone group and ADR + rutin + ozone group. Sperm functions, testosterone (T), luteinising hormone (LH), follicle stimulating hormone (FSH), testicular enzymes, oxidant/antioxidant status, C‐reactive protein, monocyte chemoattractant proteins‐1 and leukotriene B4 were determined. After ADR injection, a decline in sperm functions was observed. FSH and LH levels were increased, T level and testicular enzymes were decreased, significant enhancement in oxidative stress with subsequent depletion in antioxidants was detected and inflammatory markers were significantly elevated. Treatment with rutin and/or ozone, however, improved the aforementioned parameters. Ozone therapy alone almost completely reversed the toxic effects of ADR and restored all parameters to normal levels.     

Gallic acid and omega-3 fatty acids mitigate epididymal and testicular toxicity in manganese-treated rats

Environmental contamination by manganese is correlated with diverse health outcomes plus reproductive dysfunction. Dietary gallic acid (GA) and omega-3 fatty acids (ω-3-FA) are well reported to elicit beneficial health effects. Though, information on GA and ω-3-FA effects on manganese-induced reproductive toxicity is absent in literature. We examined the effect of GA or ω-3-FA on manganese-induced epididymal and testicular toxicity in rats, exposed to manganese (15 mg/kg b.w.) alone, in combination with GA (30 mg/kg b.w.) or ω-3-FA (20 mg/kg b.w.) by gavage for 14 consecutive days. GA or ω-3-FA significantly (p < .05) prevented manganese-mediated increase in lipid peroxidation, myeloperoxidase activity, reactive oxygen and nitrogen species production but increased antioxidant enzymes activities and glutathione level in epididymis and testes treated rats. GA or ω-3-FA enhanced the activities of testicular function marker enzymes, namely acid phosphatase (ACP), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and glucose-6-phosphate dehydrogenase (G6PD) in the treated rats. GA or ω-3-FA amelioration of manganese-induced decreases in follicle-stimulating hormone, luteinising hormone, and testosterone levels were complemented by increase (p < .05) sperm functional characteristics in treated rats. Conclusively, GA or ω-3-FA may serve as dietary supplements to improve male reproductive dysfunction associated with manganese toxicity.     

Quercetin and rutin ameliorates sulphasalazine‐induced spermiotoxicity,alterations in reproductive hormones and steroidogenic enzyme imbalance in rats

Certain dietary flavonoids exhibit protective potentials against drug‐induced male reproductive toxicities. We investigated the protective effects of quercetin and rutin on sulphasalazine‐induced alterations in steroidogenic enzyme activity, hormone profile and spermiotoxicity in rats. Sulphasalazine (SASP, 600 mg/kg bw) was administered alone or in combination with quercetin (20 mg/kg bw) or rutin (10 mg/kg bw) for 14 days. SASP treatment significantly increased relative weights of the epididymis and seminal vesicles. Also, testicular and epididymal sperm numbers (TSN, ESN), motility, daily sperm production (DSP) and acrosome reaction (AR) significantly decreased. SASP altered plasma testosterone, luteinising hormone (LH) and follicle‐stimulating hormone (FSH) levels while testicular cholesterol levels, 3β‐hydroxysteroid dehydrogenase (3β‐HSD) and 17β‐hydroxysteroid dehydrogenase (17β‐HSD) activities were decreased. Elevated malondialdehyde levels and concomitant decrease in reduced glutathione, glutathione‐S‐transferase, peroxidase and superoxide dismutase activities were evident in testis and epididymis of SASP‐treated rats. Quercetin or rutin co‐treatment with SASP significantly reversed organ weights, preserved sperm integrity, restored plasma hormone levels and increased cholesterol levels, 3β‐HSD and 17β‐HSD activities in testis. Both flavonoids also prevented oxidative stress in testis and epididymis of SASP‐treated rats. Quercetin and rutin protect against the negative effects of SASP treatment on reproductive capacity in male rats.     

Rutin ameliorates cisplatin‐induced reproductive damage via suppression of oxidative stress and apoptosis in adult male rats

Cisplatin (CP) treatment causes damage in the male reproductive system. Rutin (RUT) is a naturally occurring flavonoid glycoside that has antioxidant and anti‐inflammatory properties. This study aimed to investigate effects of RUT against cisplatin‐induced reproductive toxicity in male rats. Twenty‐one adult male Sprague Dawley rats were used. The control group received physiological saline with oral gavage during 14 days, and physiological saline was injected intraperitoneally (IP) in 10th days of study. CP Group received physiological saline during 14 days, and 10 mg kg^?1 CP was injected IP in 10th day. RUT + CP group received RUT (150 mg kg^?1) during 14 days, and 10 mg kg^?1 CP was injected IP in 10th day. Spermatological parameters (including motility, cauda epididymal sperm density, dead sperm percentage and morphological sperm abnormalities), biochemical (MDA, GSH, GSH‐px, SOD and CAT), histological (H&E dye) and immunochemistry evaluations of testicles were evaluated. CP treatment caused damage on some spermatological parameters, increased the oxidative stress and induced testicular degeneration and apoptosis when compared to the control group. However, RUT treatment mitigates these side effects when compared to the CP alone group. IT is concluded that RUT treatment may reduce CP‐induced reproductive toxicity as a potential antioxidant compound.     

Favourable effect of β‐glucan treatment against cisplatin‐induced reproductive system damage in male rats

The aim of this study was to investigate the potential beneficial effects of β‐glucan treatment against oxidative, histological and spermatological damage caused by cisplatin on the male reproductive system. Twenty‐eight Sprague Dawley male rats were used in the study. The rats were randomly divided into four equal‐sized groups: a control group, cisplatin group (7 mg/kg in a single‐dose cisplatin administered intraperitoneally), β‐glucan group (β‐glucan given at a dose of 50 mg kg^?1 d^?1 for 14 day) and a cisplatin plus β‐glucan group (cisplatin and β‐glucan administered together at the same dose). Cisplatin administration induced an increase in the level of thiobarbituric acid‐reactive substances, a lipid peroxidation indicator. It induced a decrease in enzymatic (superoxide dismutase, catalase and glutathione peroxidase) activities and nonenzymatic (reduced glutathione) antioxidant levels. In addition, cisplatin caused both histological and spermatological damage, as shown by a decrease in sperm motility and epididymal sperm concentrations and an increase in abnormal sperm rates. The β‐glucan treatment improved cisplatin‐induced oxidative, histological and spermatological damage. This study revealed that β‐glucan treatment provided prevention against male reproductive system damage caused by cisplatin. These preventative effects were likely due to its antioxidant properties.     

Acute diethyl nitrosamine and cadmium co‐exposure exacerbates deficits in endocrine balance,sperm characteristics and antioxidant defence mechanisms in testes of pubertal rats

Diethylnitrosamine (DEN) and cadmium are environmental contaminants of known poisonous consequences in animals and humans. We examined the influence of acute oral co‐exposure to DEN (10 mg/kg) and cadmium (5 mg/kg) on endocrine balance, semen and antioxidant status in rat testes. The results indicated decreases (p < 0.05) in the weight of the testis and organo‐somatic index of the testes in rats administered with either DEN or cadmium were aggravated in the co‐exposed rats. Serum concentrations of follicle‐stimulating hormone (FSH), luteinising hormone (LH) and testosterone decreased, and were more pronounced in rats co‐treated with DEN and cadmium. Enzymatic and non enzymatic antioxidant activities decreased following separate exposure to DEN and cadmium, and were increased in rats co‐treated with DEN and cadmium. The significant (p < 0.05) increases in malondialdehyde (MDA) was complemented by marked increase in sperm abnormalities, reduction in the sperm count, motility and viability compared with control. Histologically, co‐exposure to DEN and cadmium aggravates their discrete effects on the testes. Co‐exposure to DEN and cadmium elicited more severe endocrine disruption and testicular oxidative damage in rats, revealing additive adverse effects on testicular functions in rats and as such, may put exposed individual at greater risk.     

Teucrium polium attenuates carbon tetrachloride‐induced toxicity in the male reproductive system of rats

The aim of this study was to investigate the protective effects of Teucrium polium (T. polium) on carbon tetrachloride (CCl₄)‐induced male reproductive system damage. The effects of T. polium and vitamin C (Vit C) on sperm parameters, gonadotrophin and testosterone levels, oxidative status and testis tissue structure were assessed in CCl₄‐treated male rats. CCl₄ caused significant alteration of sperm parameters in epididymal and testicular tissues, a decrease in hormone levels, and a decrease in antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in testicular tissues. A noteworthy increase in malondialdehyde (MDA) level was induced in CCl₄‐treated rats with some histopathological damages on the testes compared with control group. Remarkable ameliorations were observed with respect to all the previous parameters, following the administration of CCl₄ with T. polium, and with vitamin C used as a positive control, when compared with CCl₄ alone. Teucrium polium extracts showed good antioxidant performance, suggesting its protective effect against chemically induced reprotoxicity.     

Protective effects of Fumaria parviflora L. on lead‐induced testicular toxicity in male rats

In recent years, the clinical importance of herbal drugs has received considerable attention in reducing free radical‐induced tissue injury. Oxidative stress has been proposed as a possible mechanism involved in lead toxicity that causes reproductive system failure in both human and animals. Fumaria parviflora L., a traditional herb, has been used to cure various ailments in Persian folk medicine. This study was carried out to investigate whether ethanolic extract of F. parviflora leaves could protect the male rats against lead‐induced testicular oxidative stress. Adult Wistar rats were treated with 0.1% lead acetate in drinking water with or without 200 mg kg day^?1 F. parviflora extract via gavage for 70 days. Lead acetate treatment resulted in significant reduction in testis weight, seminiferous tubules diameter, epididymal sperm count, serum testosterone level, testicular content of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Moreover, significant elevation was observed in content of malondialdehyde (MDA) in lead‐treated rats. However, co‐administration of F. parviflora extract showed a significant increase in selected reproductive parameters in lead‐treated rats. The results indicated that ethanolic extract of F. parviflora leaves has a potential to restore the suppressed reproduction associated with lead exposure and prevented lead‐induced testicular toxicity in male Wistar rats.     

Evaluation of the protective effect of quercetin against cisplatin‐induced renal and testis tissue damage and sperm parameters in rats

The protective effect of quercetin on cisplatin‐induced renal and testicular tissue damage was investigated using biochemical, histopathological and histological approaches. A total of 40 male rats were divided into 5 groups as follows: control; cisplatin alone; quercetin alone; cisplatin + quercetin; and quercetin + cisplatin. Cisplatin was administered to rats at a single dose of 7 mg kg^?1 intraperitoneal. Quercetin was administered by gavage daily for 10 days at dosage 50 mg kg^?1. At the end of the study serum, total antioxidant capacity (TAC) levels and total oxidant status (TOS) were determined. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and xanthine oxidase (XO) were studied separately in serum, renal tissue and testicular tissue. Renal and testicular morphological alterations were assessed, histopathologically. Epididymal sperm concentration, motility and morphology were investigated. Testicular and renal TAC and TOS values did not alter significantly. Renal CAT levels were increased by cisplatin and cisplatin plus quercetin groups that is reversed by administration of quercetin before cisplatin. MDA, CAT, SOD ve XO levels of testicular tissue did not differ significantly. Cisplatin and cisplatin plus quercetin groups had decreased sperm motility ratio and increased abnormal spermatozoa. Quercetin partially reverses some of the cisplatin‐related pathological effects on kidney and testis.