Cadmium-induced Testicular Toxicity Research Articles

Comparing the effects of Cyperus esculentus hydroethanolic extract and Euterpe oleracea on reproductive efficacy against cadmium-induced testicular toxicity in male rats.

Cadmium chloride (CdCl2) is an environmentally toxic pollutant that can cause reprotoxicity. Cyperus esculentus and Euterpe oleracea are potent antioxidant plants currently used to counteract the action of harmful pollutants. The present experiment was intended to evaluate and comp are the role of C. esculentus hydroethanolic extract (CHE) and E. oleracea in treating the reprotoxicity induced by CdCl2 in rats. Forty adult male rats (160-210 gm) were allocated into five groups equally. Control group: received 5 ml of normal saline (NS); the other treatment groups were injected with CdCl2 as a single dose for two weeks to induce testicular toxicity. After 14 days, the four groups were treated orally daily for two months as follows: The cadmium group (Cd) received NS, the third group (TC) was administered 800 mg/kg BW of CHE, the fourth group (TO) received 500 mg/kg BW of E. oleracea, and the fifth group (TCO) received CHE with E. oleracea. The live sperm and motility, serum testosterone, follicle-stimulating hormone (FSH), testicular superoxide dismutase (SOD), catalase (CAT), steroidogenic acute regulatory protein (StAR), 17β-hydroxysteroid dehydrogenase, and 3β-hydroxysteroid dehydrogenase (3β-HSD) were significantly increased in the TCO, TC, and TO groups compared with the Cd group. Testicular nitric oxide and malondialdehyde were elevated significantly in the Cd group compared to the TC, TO, TCO, and control groups. The fold changes of Fshβ, Lhβ, and Gnrh genes were upregulated in the TCO group compared to the Cd and control groups. The combination of CHE with E. oleracea showed improvements in rat testicles affected by cadmium toxicity via upregulated reproductive gene expression and its antioxidant effects.

Effects of chrysin in cadmium-induced testicular toxicity in the rat; role of multi-pathway regulation.

Cadmium (Cd) is a strong toxic agent and causes serious damage to testicular tissues. Chrysin (CHR) is a natural flavonoid with many effective properties, especially antioxidant, anti-inflammatory and anti-apoptotic properties. The current study describes new evidence for the ameliorative effects of CHR on oxidative stress, apoptosis, autophagy and inflammation pathways in Cd-induced testicular tissue toxicity. Thirty-five male Wistar rats were divided into five groups, control, Cd, CHR, Cd + CHR25, and Cd + CHR50. Cd was administered alone at a dose of 25mg/kg body weight or in combination with CHR 25mg/kg and CHR 50mg/kg for 7 days. Cd and CHR were administered orally. Biochemical, molecular, and histological methods were used to investigate inflammation, apoptosis, autophagy, and oxidant pathways in testicular tissue. Cd increased lipid peroxidation, JAK-2/STAT-3 levels, inflammation-related NF-κB, TNF-α, IL-1β, IL-6, COX-2, and iNOS levels, AKT-2, FOXO1, Bax, Apaf-1 and Caspase-3 levels, autophagic Beclin-1, LC3A and LC3B. The Cd also caused a decrease in the activities of antioxidant enzymes and GSH levels, antiapoptotic Bcl-2 levels. CHR, on the other hand, had the opposite effect of all these Cd-induced changes. Overall, the data of this study indicate that testicular damage associated with Cd toxicity could be ameliorated by CHR administration.

Effect of Thymus vulgaris leaf extract on cadmium-induced testicular toxicity in rats

BackgroundCadmium (Cd) is a known metallohormone which mimics the action of steroid hormones with adverse effect on testicular function. It is highly toxic and a prevalent environmental contaminant with no conventional antidote. This study investigates the possible ameliorative effects of Thymus vulgaris extract on testicular toxicity induced by Cd in male rats.ResultsThe testicular and epididymal weights, serum concentration of follicle stimulating hormone, luteinizing hormone, and testosterone were significantly (p ≤ 0.05) lower in the cadmium-treated group compared to the control. Necrosis of germ cells of the seminiferous tubules was observed in the testicular tissues of the cadmium-treated group. Administration of extract showed mild but non-significant (p ≥ 0.05) protective effect on the cadmium-induced decrease in sex hormones and sperm count as well as oxidative stress and histological changes.ConclusionThymus vulgaris leaf extract had weak ameliorative effect on cadmium-induced testicular injury in rats but with promising antioxidant activity.

Panax ginseng ameliorate toxic effects of cadmium on germ cell apoptosis, sperm quality, and oxidative stress in male Wistar rats

Panax ginseng is known to potentiate the immune system via its antioxidant properties. Cadmium as an environmental pollutant has destructive effects on body organs especially the reproductive system. This study investigated the effects of P. ginseng extract against cadmium-induced testicular toxicity in rats. In this experimental study, 50 male adult rats were randomly divided into 5 groups: A significant decrease was observed in sperm count and viability in the cadmium group versus the control group. Ginseng extract could repair these defects. Increases in apoptotic germ cells due to cadmium were significantly reduced by ginseng extract. Our results demonstrated that P. ginseng extract reduces cadmium-induced testicular toxicity, via anti-oxidative and anti-apoptotic processes.

The potential gonadoprotective effects of grape seed extract against the histopathological alterations elicited in an animal model of cadmium-induced testicular toxicity.

Grape seed extract (GSE) is a powerful antioxidant containing high levels of bioflavonoids, vitamin C and vitamin E. The aim of the work is to study the possible protective and ameliorative effects of grape seed extract in an animal model of cadmium (Cd)-induced testicular toxicity in rats. A thirty-day oral gavage study in adult male albino rats was performed using 32 animals, randomly divided into four equal groups; negative control, Cd (5 mg/k/day), GSE (100 mg/k/day), and Cd + GSE. Testicular weights were measured. Haematoxylin and eosin (H&E) staining and proliferating nuclear cell antigen (PCNA) immunohistochemistry, as a marker for proliferation were done. Morphometric parameters were assessed and subjected to statistical analysis. The H&E results showed atrophy and distortion of the seminiferous tubules (STs) with sloughing of the spermatogenic epithelium in cadmium group. The interstitial spaces were widened and showed oedema and mononuclear cell infiltrations. No remarkable changes were observed in the GSE-only group when compared to the control group. In Cd + GSE group, maintaining of the STs and their lining cells was evident. The immunohistochemical results showed marked positive PCNA immunoreactivity in both control and GSE groups, while negative immunoreaction was noticed in Cd group. Limited positive PCNA immunoreactivity was ameliorated in Cd + GSE group. Grape seed extract protected against cadmium-induced testicular toxicity in rats, reducing induced histopathological changes, and maintaining testicular histoarchitecture.

Protective effect of naringenin against cadmium-induced testicular toxicity in male SD rats

This study aimed to investigate the effect of naringenin (Nar) on cadmium (Cd)-induced testicular toxicity. Twenty-four male Sprague–Dawley (SD) rats aged 5 weeks were used. Rats were administered with 0.9% NaCl (control group), CdCl2 (2 mg/kg b.w. intraperitoneally), Nar (50 mg/kg b.w, orally), and CdCl2 + Nar (2 mg/kg b.w intraperitoneally and 50 mg/kg b.w. orally, respectively) for 4 weeks. Results showed that body weight, relative testis weights, and sperm quality decreased in the Cd-treated group, and Cd accumulated in serum and testes. Pathological examination showed that Cd can cause testicular damage. Cd decreased the serum concentrations of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. It also decreased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Moreover, exposure to Cd resulted in decreased content of reduced glutathione (GSH) and total antioxidant capacity (T-AOC) concentrations, as well as increased malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents. Cd also provoked testis autophagy by upregulating the expression of the autophagy-related proteins P62 and LC3 II. However, the combined administration of Nar and Cd significantly attenuated the Cd-induced negative effects by increasing the body weight, relative testis weights, and sperm quality and by decreasing testicular damage. Simultaneous supplementation of Nar and Cd markedly restored the decreased levels of GnRH, FSH, LH, testosterone, GSH, and T-AOC and the activities of SOD, CAT, and GPx caused by Cd treatment. Nar further suppressed MDA and H2O2 production and protected the testes from Cd-induced autophagy by downregulating P62 and LC3 II expression. Therefore, Nar protected the testes from Cd-induced toxicity.

Protective Effect of Graviola (Annona muricata) Leaves Extract Against Cadmium-Induced Testicular Toxicity In Male Albino Rats

Graviola (Annona muricata), an edible plant belonging to the Annonaceae family, has a long history in traditional medicine due to its wide range of therapeutic effects on many ailments. This study was planned to assess the protective potentials of Graviola leaves extract (GLE) on cadmium-induced testicular damage in male albino rats. The study was conducted on 32 male adult Wistar rats randomly divided into four groups (n=8/each). A (control group); B (GLE, 100 mg/kg); C (cadmium chloride (CdCl2), 5 mg/kg) and D (GLE, 100 mg/kg + CdCl2 5 mg/kg). All administrations were performed by daily gavage for 8 weeks. Blood, testes, and epididymis were harvested for biochemical and histological investigations. In addition to sperm analysis, sperm DNA comet assay, and apoptotic indices. Results revealed that GLE significantly reversed (p < 0.05) testicular oxidative stress induced by CdCl2, maintained male sex hormones levels, and restored testis architecture via increasing the testicular antioxidant status. GLE co-treatment significantly increased (p < 0.05) sperm count, motility, viability, and DNA integrity along with significantly reducing sperm DNA damage and sperm head abnormality in comparison with CdCl2 group. Additionally, GLE protected germ cells from Cd-induced apoptosis. In conclusion, results of the present study confirmed that GLE has potent antioxidant potentials and cytoprotective capacity against the deleterious effects of CdCl2 on testicular tissue by reducing cellular oxidative stress prompted by the generation of the reactive oxygen species.

Effect of the combination between empagliflozin and calcipotriol on cadmium-induced testicular toxicity in rats

The aim of this study was to assess the effect of empagliflozin and/or calcipotriol on cadmium-induced testicular toxicity in rats. Sixty male Wistar rats were divided into 6 equal groups: Control; cadmium; cadmium + empagliflozin; cadmium + calcipotriol; cadmium + Carboxymethyl cellulose and cadmium + empagliflozin + calcipotriol. Testicular enzymes, serum testosterone, luteinizing hormone and follicle stimulating hormone were measured. Also, testicular tissue antioxidant enzymes, interleukin-6 (IL-6), transforming growth factor beta 1 (TGF-β1) and sperm characteristics were determined. Parts of the testes were subjected to histopathological and immunohistochemical examination. Empagliflozin/calcipotriol combination restored the testicular enzymes, sperm characteristics, hormonal profile and the antioxidant defenses compared to the use of each of these drugs alone. Also, this combination significantly ameliorated the inflammatory processes and induced significant improvement of the histopathological, and immunohistochemical picture compared to the use of each of these drugs alone. So, empagliflozin/calcipotriol combination might represent a promising therapeutic modality for amelioration of cadmium-induced testicular toxicity.

Protective role of glutamine against cadmium-induced testicular dysfunction in Wistar rats: Involvement of G6PD activity

BackgroundEndocrine disruptor such as cadmium has been widely reported to cause testicular toxicity, which contributes to recent decline in male fertility worldwide. Glutamine, the most abundant amino acid in the body has been demonstrated to exert protective effects in cellular toxicity. However, its role in testicular toxicity is unknown. The present study is therefore aimed at investigating the effects of glutamine supplementation on cadmium-induced testicular toxicity, and the possible involvement of glucose-6-phosphate dehydrogenase (G6PD) activity. Materials and methodMale Wistar rats weighing 160–190 g were allotted into 4 groups (n = 5/group): The groups received vehicle (distilled water; p.o.), glutamine (1gkg−1; p.o.), cadmium chloride (5mgkg−1p.o.) and Cadmium chloride plus glutamine respectively, daily for 30 days. Biochemical and histological analyses were performed with appropriate method. ResultsAdministration of cadmium significantly decreased body weight, sperm count, motility and viability, as well as altered sperm morphology and progressivity. Cadmium also caused atrophy of the seminiferous tubule in addition to disrupted testicular architecture, lumen, Sertoli cells and spermatogonia. Similarly, serum and testicular aspartate transaminase, and malondialdehyde significantly increased, and G6PD, glutathione, nicotinamide adenine dinucleotide phosphate and nitric oxide significantly decreased with corresponding decrease in follicle stimulating hormone, luteinizing hormone and testosterone in cadmium-treated animals compared with control groups. However, supplementation with glutamine attenuated these alterations. ConclusionThe present study demonstrates that cadmium induces testicular dysfunction that is attributable to defective G6PD and accompanied by increased lipid peroxidation and impaired NO-dependent endothelial function. Interestingly, glutamine supplementation ameliorates cadmium-induced testicular dysfunction through enhancement of G6PD activity.

The ameliorative effect of methanolic red carrot extract and vitamin E against cadmium-induced testicular toxicity in rats

The current study aimed to investigate the effects of methanolic red carrot extract (MRCE) against cadmium intoxication on testis of adult Wister albino male rats. For that purpose, forty eight Wister albino male rats were randomly divided into four groups (12 rats per group). Group 1 (normal control), animals received corn oil. Group 2 (cadmium group), animals received cadmium chloride (CdCl2) at a dose of (5 mg/ kg BW). Group 3 (cadmium &Vit. E group), animals received vitamin E at a dose of (400mg/kg BW) and CdCl2at a dose of (5 mg/kg BW). Group 4 (cadmium & red carrot extract, animals received methanol: water red carrot extract (1:1) at a dose of 400 mg/kg and CdCl2 at a dose of (5 mg/kg BW). All rats were received their corresponding treatment orally by gastric gavage daily for 4 weeks. Result of organ weight analysis in Cd –exposed rats showed a decrease in testes weight. On the contrary, MRCE and vitamin E prophylactic co-treatments with cadmium showed significant increase in testis weights in comparison to cadmium group (P<0.05). Moreover, sperm concentrations were reduced markedly with cadmium while they were upturned greatly after prophylactic co-treatment with either MRCE or vitamin E (P<0.05). Moreover, cadmium induced a significant increase in testicular malondialdehyde (MDA) and significant decrease of total antioxidant capacity (TAC) but both MRCE and vitamin E supplementation succeeded markedly to produce a significant reduction in testicular MDA and noticeable increase of TAC level. Thus, MRCE and vitamin E could be considered optimal prophylactic treatments to protect the testis of rats from cadmium intoxication.

Diacerein Downregulates NLRP3/Caspase-1/IL-1β and IL-6/STAT3 Pathways of Inflammation and Apoptosis in a Rat Model of Cadmium Testicular Toxicity.

The potential gonadal protective effect of diacerein (DCN) and its underlying mechanisms were studied in a rat model of cadmium-induced testicular toxicity. The rats received DCN (50mg/kg/day, p.o.) for 10days and one injection of CdCl2 (2mg/kg, i.p.) on day 9. Cadmium significantly declined serum testosterone and significantly raised interleukin-1β, interleukin-6, interleukin-18, tumor necrosis factor-α, caspase-1, phosphorylated signal transducer and activator of transcription-3 (pSTAT3), nuclear factor-κB p65, Bax, and caspase-3 in rat testes. DCN significantly ameliorated the changes in the biochemical measurements observed with CdCl2 insult. Additionally, DCN preserved the normal testicular architecture, maintained spermatogenesis, and lowered the expression of NOD-like receptor family protein 3 (NLRP3) inflammasome in testes of rats that received CdCl2. It was concluded that DCN significantly protected the gonads of male rats exposed to cadmium toxicity through modulation of NLRP3/caspase-1/IL-1β and IL-6/STAT3 pathways of inflammation and apoptosis.

Cadmium-Induced Testicular Toxicity in Mice: Subacute and Subchronic Route-Dependent Effects

This study aimed to compare Cd exposure by intraperitoneal (i.p.) and oral routes, evaluating the testicular subacute and subchronic effects. Adult male mice were separated into three groups subdivided according to the experimental period (7 and 42days after Cd exposure: subacute and subchronic effects, respectively): one group received water and two groups received CdCl2 (1.2mg/kg i.p. and 24mg/kg oral). The testicular concentration of essential minerals and Cd, activity of antioxidant enzymes and markers of oxidative stress, histology, and testicular histomorphometry were evaluated. The subacute effect of oral Cd showed reduced Fe concentration, while Ca and Cu increased in this route. The subchronic effect promoted decreasing in Mg in i.p. and oral routes, whereas Zn decreased only in the oral, and the Fe concentration did not change. SOD activity decreased in the oral subacute evaluation and in both pathways, i.p. and oral routes, in the subchronic evaluation, while GST activity increased, and MDA concentration decreased. Labeling of apoptotic cells was increased in the subacute and subchronic evaluation. Seminiferous epithelium degeneration, death of germ cells, and Leydig cell damages occurred in i.p. and oral routes. However, these damages were more intense in the oral route, mainly evaluating the subchronic effects. The results confirm that the severity of Cd-induced testicular injury depends on the pathway, as well as the duration of exposure.

Protective Effect of Ganoderma Triterpenoids on Cadmium-Induced Testicular Toxicity in Chickens.

Studies have shown that cadmium can cause chicken testicular damage, but a protective effect of Ganoderma triterpenoids on cadmium-induced testicular damage in chickens has not yet been reported. The present study was designed to research the protective effect of Ganoderma triterpenoids on cadmium-induced testicular damage in chicken. Eighty healthy 7-day-old Hyline egg laying chickens were randomly divided into four groups with 20 in each group. The control group was fed with normal full-fodder, the model group was fed with normal full-fodder with 140mg/kg of CdCl2, the Ganoderma triterpenoid treatment group was fed with a full-fodder diet containing 140mg/kg of CdCl2 and 0.5mL of Ganoderma triterpenoid solution (20mg/mL), and the Ganoderma triterpenoid group was fed normal full-fodder and 0.5mL of Ganoderma triterpenoid solution (20mg/mL) gavage. The chickens were euthanized at 20, 40, and 60days, respectively, and the testes were harvested. The changes of cadmium contents, the antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)), peroxide (malondialdehyde (MDA)), inflammatory factors (interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α)), and apoptosis-related proteins (Bax, Bcl-2, and Caspase-3) were detected. The pathological sections of the testes were made at the same time. The results suggested that Ganoderma triterpenoids could reduce the accumulation of cadmium in testis tissue; reduce the content of IL-1β, IL-6, and TNF-α in cadmium poisoning testis; significantly increase the activity of SOD and GSH-Px; decrease the content of MDA; regulate the expression of Bax, Caspase-3, and Bcl-2; and reduce the damage of testicular tissue. The results showed that Ganoderma triterpenoids have a protective effect on cadmium-induced testicular injury in chicken.

Cadmium-induced testicular damage is associated with mineral imbalance, increased antioxidant enzymes activity and protein oxidation in rats

AimsCurrently, the spectrum of pathological manifestations associated with cadmium-induced testicular toxicity is poorly understood. Thus, we investigated the impact of cadmium (Cd) exposure on testicular mineral bioavailability, activity of antioxidant enzymes, testicular structure and germ cells ultrastructure Main methodsCadmium chloride was administered in a single dose to thirty rats equally randomized into five groups: Saline, 0.9% NaCl; Cd1 – Cd4, 0.67, 0.74, 0.86 and 1.1mgCd/kg. Seven days after Cd exposure, animals were euthanized and testes were collected for biochemical analysis, as well as light, scanning and transmission electron microscopy. Key findingsCadmium exposure induced dose-dependent testicular toxicity. Tubular and intertubular compartments were targets of Cd and calcium (Ca) deposits, marked structural and ultrastructural pathologic remodeling, and a reduced distribution of iron, selenium, magnesium, copper, zinc and total protein. Despite upregulation in antioxidant enzyme activities (i.e. catalase [CAT] and superoxide dismutase [SOD]), morphologic and molecular testis damage such as protein oxidation was not prevented, especially with higher doses of Cd. As non-degenerated tissue areas also presented Ca deposits, Ca imbalance was not only a consequence but also a cause of Cd-induced testis toxicity and germ cell death SignificanceTaken together, our findings indicated that Cd exposition induced dose-dependent testicular dystrophic calcification, which was associated with increased antioxidant enzymes activity and protein oxidation, mineral imbalance, germ cell calcification and death in rats. Although increased CAT and SOD activity represents a counter-regulatory reaction to cadmium-induced toxicity, this reaction is insufficient to prevent testicular pathological remodeling.

Protective effect of Lycium barbarum polysaccharides against cadmium-induced testicular toxicity in male mice.

The present study was performed to determine whether Lycium barbarum polysaccharides (LBPs) would protect mice against cadmium (Cd)-induced testicular toxicity. Seventy-two male mice were randomly divided into six groups with twelve mice per group. Four groups were administered orally with cadmium chloride (5.0 mg per kg body weight) for 35 days and treated in combination with LBPs (0, 10.0, 33.3 or 100 mg kg-1) from one week before exposure to Cd until the end of the experiment. The other two groups were administered orally with vehicle or LBP (100 mg kg-1) only. Pretreatment with LBP ameliorated the Cd-induced reduction in the body weights, sperm motility as well as the level of testosterone in serum. Moreover, Cd-induced increase in the abnormal sperms was reduced and effects of Cd on the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were reversed. Histopathological examination further confirmed that the LBPs effectively attenuated Cd-induced degeneration of seminiferous tubules. Thus, LBPs attenuated Cd-induced testicular injury by improving the activity of antioxidant enzymatic activity and lowering the oxidative stress, so it could be a potential auxiliary therapeutic agent for Cd-induced testicular toxicity.

Ameliorative effect of propolis on the cadmium-induced reproductive toxicity in male albino rats

Propolis is a potent antioxidant and a free radical scavenger. The present study aimed to investigate protective effects of propolis extract on cadmium-induced testicular damage, apoptosis, HIF-1α expression and toxicity in rat's testis tissue.A total of 32 male rats were equally divided into four study groups namely, control, Cd (1mg/kg/day), Cd+propolis (50mg/kg/day) and propolis. The rats were decapitated under ketamine anesthesia and their testes tissues were removed. Serum testosterone, tissue malondialdehyde and HIF-1α levels, HIF-1α expression, apoptosis and histopathological damage scores were then compared.In the Cd group, the diameters of seminiferous tubules, tubular biopsy score of Johnsen and serum testosterone levels were decreased compared control group, but tissue HIF-1α and tissue MDA levels was higher than control group. The immunoreactivity of HIF-1α and the number of apoptotic cells were increased in Cd group. Furthermore, the propolis treated group showed an improved histological appearance in the Cd group.Thus, the results suggest that propolis acts as a potent protective agent against Cd-induced testicular toxicity in rats.

Cadmium-Induced Testicular Toxicity, Oxidative Stress and Histopathology in Wistar Rats: Sustained Effects of Polyphenol-Rich Extract of Vernonia Amygdalina (Del.) Leaf

Background: Cadmium (Cd) is a toxic heavy metal of both environmental and occupational concerns. The health impact of ethno-botanical approaches in attempts to ameliorate its deleterious effects in biological systems should be an area of scientific interest since established therapies are often burdened with undesirable side effects. Aim: To determine the effects of polyphenol-rich extract of the leaf of Vernonia amygdalina (PEVA) on Cd-induced testicular toxicity, oxidative stress, and histopathology in Wistar rats. Materials and Methods: A total of twenty five (25) male Wistar rats were divided into five groups as follows: Group 1 (Control) received distilled water (0.2 ml/100 g i.p.) for 5 consecutive days and thereafter left untreated for 28 days. Group 2 received Cd alone at 5 mg/kg (i.p.) for 5 consecutive days. Group 3 was pre-treated with Cd as Group 2 and thereafter left untreated for a period of 28 days, whereas Groups 4 and 5 were pre-treated with Cd as Group 2 and thereafter received PEVA (orally) at two dose levels (200 and 400 mg/kg, respectively) for 28 days. Results: Cd administration induced reproductive toxicity as evidenced by lowered level of follicle stimulating hormone, luteinizing hormone, and testosterone (P < 0.05); perturbation of sperm characterization (P < 0.05); deleterious disruptions of the antioxidant system as evidenced by lowered levels of reduced glutathione and superoxide dismutase as well as elevation in thiobarbituric acid reactive substances level (P < 0.05); decrease in relative testicular weight (P < 0.05); and severe disseminated necrosis of the seminiferous tubules with terminally undifferentiated/necrotic cells as revealed by the histopathological examination. These conditions were sustained following administration of the two dose levels of PEVA. Conclusion: PEVA administration is not a suitable therapeutic choice for fertility enhancement in male Wistar rat model of Cd-induced decline in reproductive function.

Anti-Apoptotic and Anti-Oxidant Effects of Caffeic Acid Phenethyl Ester on Cadmium-Induced Testicular Toxicity in Rats.

Cadmium (Cd) is a serious environmental and occupational contaminant and may represent a serious health hazard to humans and other animals. Cd is reported to induce the generation of reactive oxygen species, and induces testicular damage in many species of animals. The goal of our study was to examine the anti-apoptotic and anti-oxidant effects of caffeic acid phenethyl ester (CAPE) on Cd-induced oxidative stress, apoptosis, and testicular injury in rats. A total of 40 male Wistar albino rats were divided into four groups: control, CAPE alone, Cd-treated, and Cd-treated with CAPE; each group consisted of 10 animals. To induce toxicity, Cd (1 mg/kg body weight) was dissolved in normal saline and subcutaneously injected into rats for 30 days. The rats in CAPE-treated group were given a daily dose of 10 μmol/kg body weight of CAPE by using intraperitoneal injection. This application was continued daily for a total of 30 days. To date, no examinations of the anti-apoptotic and anti-oxidant properties of CAPE on Cd-induced apoptosis, oxidative damage, and testicular injury in rat testes have been reported. CAPE-treated animals showed an improved histological appearance and serum testosterone levels in Cd-treated group. Our data indicate a significant reduction in the number of apoptotic cells in testis tissues of the Cd-treated group with CAPE treatment. Moreover, CAPE significantly suppressed lipid peroxidation, compensated deficits in the anti-oxidant defenses in testes tissue resulted from Cd administration. These findings suggest that the protective potential of CAPE in Cd toxicity might be due to its anti-oxidant and anti-apoptotic properties, which could be useful for achieving optimum effects in Cd-induced testicular injury.

Thymoquinone therapy abrogates toxic effect of cadmium on rat testes.

The protective effect of thymoquinone was investigated against cadmium-induced testicular toxicity in rats. Testicular toxicity was induced by a single intraperitoneal (i.p.) injection of cadmium chloride (2mgkg(-1) ). Thymoquinone treatment (10mgkg(-1) day(-1) , i.p.) was applied for five consecutive days, starting 3days before cadmium administration. Thymoquinone significantly attenuated the cadmium-induced decreases in serum testosterone, and testicular reduced glutathione and superoxide dismutase activity and significantly decreased the elevations of testicular malondialdehyde, nitric oxide and cadmium ion levels resulted from cadmium chloride administration. Also, thymoquinone ameliorated the cadmium-induced testicular tissue injury observed by histopathological examination. In addition, thymoquinone significantly decreased the cadmium-induced expression of inducible nitric oxide synthase, tumour necrosis factor-α, cyclooxygenase-2, nuclear factor-κB and caspase-3 in testicular tissue. It was concluded that thymoquinone, through its antioxidant and anti-inflammatory activities, may represent a potential candidate to protect the testes against the detrimental effect of cadmium exposure.

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.