Protective Effect of Selenium on Aflatoxin B1-Induced Testicular Toxicity in Mice

Aflatoxins have been considered as one of the major risk factors of male infertility, and aflatoxin B1 (AFB1) is the most highly toxic and prevalent member of the aflatoxins family. Selenium (Se), an essential nutritional trace mineral for normal testicular development and male fertility, has received extensive intensive on protective effects of male reproductive system due to its potential antioxidant and activating testosterone synthesis. To investigate the protective effect of Se on AFB1-induced testicular toxicity, the mice were orally administered with AFB1 (0.75 mg/kg) and Se (0.2 mg/kg or 0.4 mg/kg) for 45 days. We found that that Se elevated testes index, sperm functional parameters (concentration, malformation, and motility), and the level of serum testosterone in AFB1-exposed mice. Moreover, our results showed that Se attenuated the AFB1-induced oxidative stress and the reduction of testicular testosterone synthesis enzyme protein expression such as steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage (P450scc), and 17β-hydroxysteroid dehydrogenase (17β-HSD) in AFB1-exposed mice. These results demonstrated that Se conferred protection against AFB1-induced testicular toxicity and can be attributed to its antioxidant and increased testosterone level by stimulating protein expression of StAR and testosterone synthetic enzymes.     

Remedial effect of DL-α-lipoic acid against adriamycin induced testicular lipid peroxidation

Adriamycin (ADR), a cytotoxic antineoplastic drug is used in the treatment of various solid tumors. However, its efficacy continues to be challenged by significant toxicities including testicular toxicity. In the present study, the effect of lipoic acid, a "universal antioxidant" was investigated on ADR induced peroxidative damages in rat testis. Adult male albino rats of Wistar strain were administered ADR (1 mg/kg body weight, i.v.) once a week for 10 weeks. ADR injected rats showed a significant decline in the activities of enzymic antioxidants (catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase) and non-enzymic antioxidants (reduced glutathione, Vitamin A, Vitamin C and Vitamin E) with high malondialdehyde levels. The extent of testicular toxicity was evident from the decreased activities of testicular marker enzymes (sorbitol dehydrogenase and glucose-6-phosphate dehydrogenase). Treatment with lipoic acid (35 mg/kg body weight, i.p.) one day prior to ADR administration, maintained near normal activities of the enzymes and significantly reduced lipid peroxidation, thereby proving it to be an effective cytoprotectant.     

The dynamic assessment of toxicity and pathological process of DEHP in germ cells of male Sprague Dawley rats

Di-(2-ethylhexyl) phthalate is representative of Phthalate esters (PAEs), which is one of the most widely used plasticizer and known to act as a reproductive toxicant. However, little is known about the toxicity and pathological process of DEHP exposure in male reproductive system in terms of different concentrations and time points. In this study, peripubertal male Sprague Dawley rats were continually exposed to different DEHP doses (100 mg/kg, 500 mg/kg, and 900 mg/kg) and periods (7 days, 14 days, 21 days, 28 days, and 35 days) during critical periods for sexual maturity. The reproductive parameters have been investigated, including testicular morphology, serum testosterone level, and testicular P450scc, 3β-HSD, and PCYP17 levels. We observed disarrangement of testicular spermatogenic epithelium coupled with decrease of serum testosterone, testicular P450scc, 3β-HSD, and PCYP17 levels, and these changes were more obvious with increase of both the exposure time and dosage. Then trend of the time-dose response to DEHP exposure and the pathological process in germ cells were estimated. The results of this study suggested that DEHP exposure could affect the male reproductive system and the degree of adverse effect depended on the dose and extent of exposure.     

Modulatory role of lipoic acid on adriamycin-induced testicular injury

The present study investigated the protective efficacy of dl-alpha-lipoic acid (LA) on adriamycin (ADR)-induced oxidative damage in rat testis. Adult male albino rats of Wistar strain were administered ADR (1 mg/kg body weight, i.v.), once a week for 10 weeks. ADR injected rats showed increased oxidative stress with a concomitant decrease in cellular thiols. The mRNA level for phospholipid hydroperoxide glutathione peroxidase (PHGPx) was also significantly decreased by ADR administration. Transmission electron microscopic (TEM) observations of testicular germ cells revealed abnormal ultrastructural changes in ADR treated rats. Treatment with lipoic acid (35 mg/kg body weight, i.p.) 1 day prior to ADR administration, effectively reverted these abnormal changes towards normalcy. These findings indicate a cytoprotective role of LA in this experimental model of testicular toxicity.     

Protective Effect of Selenium on Nicotine-Induced Testicular Toxicity in Rats

Effect of exogenous selenium at a dose of 10 mug/kg body weight on the testicular toxicity induced by nicotine in rats was investigated. Male albino rats were maintained for 60 days as follows: (1) control group (normal diet), (2) nicotine group (0.6 mg /kg body weight), (3) selenium (10 microg/kg body weight), and (4) nicotine (0.6 mg/kg body weight) + selenium (10 microg/ kg body weight). Administration of nicotine caused reduction in sperm count and sperm motility. Activity of HMG CoA reductase and concentration of cholesterol were increased in the testes of the nicotine administered group. Activities of testicular enzymes 3beta hydroxysteroid dehyrogenase (3 betaHSD), 17beta hydroxysteroid dehyrogenase (17 betaHSD) were decreased. Levels of testosterone in the serum were also reduced. However, the extent of these alterations was lesser in the group administered with nicotine along with selenium. Analysis of plasma revealed reduced quantity of cotinine in the group co-administered with nicotine along with selenium in comparison with the nicotine group. Nondetectable levels of nicotine were present in the co-administered group. This indicates altered metabolism of nicotine when administered along with selenium.     

In vivo effects of cadmium on calmodulin and calmodulin regulated enzymes in rat brain.

Effect of chronic cadmium (Cd) exposure and the influence of diethyldithiocarbamate (DDC) on Cd absorption was studied on the brain of young male Wistar rats. A significant amount of Cd accumulated in cerebral cortices of rats after 4 weeks of Cd (6 mg/kg body wt) exposure (through gastric intubation). The biological activity of calmodulin (CaM) decreased significantly (p less than 0.001) in the cerebral cortices of these animals in comparison to the control group. 3'-5' Phosphodiesterase and synaptic membrane Ca(2+)-Mg(2+) ATPase were also significantly affected (p less than 0.01 and p less than 0.001 respectively). However, Cd treatment did not alter synaptic membrane adenylate cyclase activity and DDC (9.2 mg/kg body wt, intraperitoneal) treatment along with Cd (6 mg/kg body wt) enhanced Cd accumulation in cerebral cortices of treated animals resulting in an increased inhibition of CaM and CaM dependent enzymes. These data suggest that Cd may be acting via binding to CaM and uncoupling it from its normal cellular control of calcium.     

Ellagic acid improved diabetes mellitus-induced testicular damage and sperm abnormalities by activation of Nrf2

Diabetes mellitus induces testicular damage, increases sperm abnormalities, and impairs reproductive dysfunction due to induction of endocrine disturbance and testicular oxidative stress. This study evaluated the reproductive protective effect of ellagic acid (EA) against testicular damage and abnormalities in sperm parameters in Streptozotocin (STZ)-induced diabetic rats (T1DM) and examined some possible mechanisms of protection. Adult male rats were segregated into 5 groups (n = 12 rat/each) as control, control + EA (50 mg/kg/day), T1DM, T1DM + EA, and T1DM + EA + brusatol (an Nrf-2 inhibitor) (2 mg/twice/week). All treatments were conducted for 12 weeks, daily. EA preserved the structure of the seminiferous tubules, prevented the reduction in sperm count, motility, and viability, reduced sperm abnormalities, and downregulated testicular levels of cleaved caspase-3 and Bax in diabetic rats. In the control and diabetic rats, EA significantly increased the circulatory levels of testosterone, reduced serum levels of FSH and LH, and upregulated Bcl-2 and all steroidogenic genes (StAr, 3β-HSD1, and 11β-HSD1). Besides, it reduced levels of ROS and MDA but increased levels of GSH and MnSOD and the transactivation of Nrf2. All these biochemical alterations induced by EA were associated with increased activity and nuclear accumulation of Nrf2. However, all these effects afforded by EA were weakened in the presence of brusatol. In conclusion, EA could be an effective therapy to alleviated DM-induced reproductive toxicity and dysfunction in rats by a potent antioxidant potential mediated by the upregulation of Nrf2.     

Neuroprotective Effects of Alpha Lipoic Acid on Haloperidol-Induced Oxidative Stress in the Rat Brain

Haloperidol is an antipsychotic drug that exerts its' antipsychotic effects by inhibiting dopaminergic neurons. Although the exact pathophysiology of haloperidol extrapyramidal symptoms are not known, the role of reactive oxygen species in inducing oxidative stress has been proposed as one of the mechanisms of prolonged haloperidol-induced neurotoxicity. In the present study, we evaluate the protective effect of alpha lipoic acid against haloperidol-induced oxidative stress in the rat brain. Sprague Dawley rats were divided into control, alpha lipoic acid alone (100 mg/kg p.o for 21 days), haloperidol alone (2 mg/kg i.p for 21 days), and haloperidol with alpha lipoic acid groups (for 21 days). Haloperidol treatment significantly decreased levels of the brain antioxidant enzymes super oxide dismutase and glutathione peroxidase and concurrent treatment with alpha lipoic acid significantly reversed the oxidative effects of haloperidol. Histopathological changes revealed significant haloperidol-induced damage in the cerebral cortex, internal capsule, and substantia nigra. Alpha lipoic acid significantly reduced this damage and there were very little neuronal atrophy. Areas of angiogenesis were also seen in the alpha lipoic acid-treated group. In conclusion, the study proves that alpha lipoic acid treatment significantly reduces haloperidol-induced neuronal damage.     

Chelation therapy and vanadium: effect on reproductive organs in rats

Present investigation was planned to evaluate the therapeutic effectiveness of chelating agents against vanadium intoxication on blood and reproductive organs of rats. Male and female albino rats were injected vanadyl sulphate (7.5 mg/kg, po, for 21 days, 5 days in a week). Chelating agents tiron (T) alone and in combination with lipoic acid (LA), vitamin E (vit E) and selenium (Se) were given for 2 days/week. With the administration of vanadyl sulphate to rats fructose level in seminal vesicles was significantly (P< or =0.05) declined. The activities of alkaline phosphatase and adenosine triphosphatase were also decreased, whereas glycogen content and acid phosphatase activity increased in testis, seminal vesicles, ovaries and uterus after toxicant exposure. Significant changes in serum transaminases, serum alkaline phosphatase and lactate dehydrogenase were recouped by chelation therapy. Lipid peroxidation, reduced glutathione level and triglycerides levels altered significantly after exposure to vanadium in rats. The ultrastructural damage in spermatogenic stages in treated animals showed recovery pattern after therapy. Co-treatment with antioxidants restored these activities. The most effective combination was tiron + selenium followed by tiron + vitamin E, and tiron + lipoic acid.     

Therapeutic Potential of Date Palm Pollen for Testicular Dysfunction Induced by Thyroid Disorders in Male Rats

Hyper- or hypothyroidism can impair testicular function leading to infertility. The present study was designed to examine the protective effect of date palm pollen (DPP) extract on thyroid disorder-induced testicular dysfunction. Rats were divided into six groups. Group I was normal control. Group II received oral DPP extract (150 mg kg^-1), group III (hyperthyroid group) received intraperitoneal injection of L-thyroxine (L-T4, 300μg kg^-1; i.p.), group IV received L-T4 plus DPP extract, group V (hypothyroid group) received propylthiouracil (PTU, 10 mg kg^-1; i.p.) and group VI received PTU plus DPP extract. All treatments were given every day for 56 days. L-T4 or PTU lowered genital sex organs weight, sperm count and motility, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone (T), testicular function markers and activities of testicular 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD). Moreover, L-T4 or PTU increased estradiol (E2) serum level, testicular oxidative stress, DNA damage and apoptotic markers. Morphometric and histopathologic studies backed these observations. Treatment with DPP extract prevented LT4- or PTU induced changes. In addition, supplementation of DPP extract to normal rats augmented sperm count and motility, serum levels of LH, T and E2 paralleled with increased activities of 3β-HSD and 17β-HSD as well as testicular antioxidant status. These results provide evidence that DPP extract may have potential protective effects on testicular dysfunction induced by altered thyroid hormones.     

Lipoic Acid Increases Hippocampal Choline Acetyltransferase and Acetylcholinesterase Activities and Improvement Memory in Epileptic Rats

In the present study we investigated the effect of seizures on rat performance in the Morris water maze task, as well as on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in rat hippocampus. Wistar rats were treated with 0.9% saline (i.p., control group), lipoic acid (20 mg/kg, i.p., LA group), pilocarpine (400 mg/kg, i.p., pilocarpine group), and the association of LA (20 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before of administration of LA (LA plus pilocarpine group). After the treatments all groups were observed for 1 h. The effect of lipoic acid administration was observed on reference and working spatial memory of seized rats. The ChAT and AChE activities were measured using spectrophotometric methods and the results compared to values obtained from saline and pilocarpine-treated animals. Its activity was also determined after behavioral task. Results showed that pretreatment with lipoic acid did not alter reference memory when compared to saline-treated animals. In the working memory task, we observed a significant day’s effect with significant differences between control and pilocarpine-induced seizures and pretreated animals with lipoic acid. In LA plus pilocarpine group was observed a significantly increased in ChAT and AChE activities, when compared to pilocarpine group. Results showed that acute administration of lipoic acid alone did not alter hippocampal ChAT and AChE activities. Our findings suggest that seizures caused cognitive dysfunction and a decrease of ChAT and AChE activities that might be related, at least in part, to the neurological problems presented by epileptic patients. Lipoic acid can reverse cognitive dysfunction observed in seized rats as well as increase the ChAT and AChE activities in hippocampus of rats prior to pilocarpine-induced seizures, suggesting that this antioxidant could be used in clinic treatment of epilepsy.     

Beneficial effects of DL-alpha-lipoic acid on cyclophosphamide-induced oxidative stress in mitochondrial fractions of rat testis

The present study investigated the protective efficacy of dl-alpha-lipoic acid on the peroxidative damage and abnormal antioxidant levels in the mitochondrial fraction of testis in cyclophosphamide (CP) administered rats. Male Wistar rats of 140+/-20 g were categorized into four groups. Two groups were administered CP (15 mg/kg body weight once a week for 10 weeks by oral gavage) to induce testicular toxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight intraperitoneally once a week for 10 weeks, 24 h prior to CP administration). A vehicle-treated control group and a lipoic acid drug control group were also included. The mitochondrial fraction of untreated CP-exposed testis showed 1.84-fold increase in lipid peroxidation, along with a significant (P<0.001) increase in hydrogen peroxide levels. In CP-exposed rats, we observed abnormal changes in the activities/levels of mitochondrial enzymic (superoxide dismutase, glutathione peroxidase and glutathione reductase) and non-enzymic (reduced glutathione, ascorbate and alpha-tocopherol) antioxidants. CP-treated rats also showed decline in the activities of mitochondrial enzymes such as succinate dehydrogenase, malate dehydrogenase and isocitrate dehydrogenase. In contrast, rats pretreated with lipoic acid showed normal lipid peroxidation and antioxidant defenses, thereby showing the protection rendered by lipoic acid.     

Effect of DL-alpha-lipoic acid on cyclophosphamide induced lysosomal changes in oxidative cardiotoxicity

Cyclophosphamide (CP), one of the widely prescribed antineoplastic drugs can cause fatal cardiotoxicity. The present study is aimed at evaluating the cardioprotective role of lipoic acid in CP induced toxicity. Male albino rats of Wistar strain were divided into four groups and treated as follows: Group I served as control, Group II received a single dose of CP (200 mg/kg b.wt., i.p.), Group III received lipoic acid (25 mg/kg b.wt., orally) for 10 days, and Group IV received CP immediately followed by lipoic acid for 10 days. In CP administered rats, the levels of protein carbonyl and 8-hydroxy-2-deoxyguanosine were increased significantly (P<0.001) indicating oxidative changes in the heart tissue. The activities of lysosomal acid hydrolases, beta-Glu, beta-Gal, NAG, Cat-D and ACP increased significantly (P<0.001) in the serum as well as in the heart tissue after CP administration. An increase in hydroxyproline was observed in CP induced rats. Lipoic acid effectively reverted these abnormal biochemical changes to near normalcy. These observations highlight the protective role of lipoic acid in CP induced cardiotoxicity.     

Effects of a testicotoxic dose of cadmium on the liver and drug metabolism in the rat

1. The effect of an acute testicotoxic dose of cadmium (CdCl2.H2O, 2.0 mg/kg i.p.) on liver morphology and drug-metabolizing enzyme activities were studied in adult male and female rats. 2. Cd treatment to female rats caused a slight and reversible decrease in hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and aminopyrine N-demethylase (APND) activities. 3. No significant changes were noted in the liver morphology, serum alanine aminotransferase activities, enzyme induction by phenobarbital and 3-methylcholanthrene, and glucuronosyl-transferase (GT) and glutathione S-transferase (GST) activities. 4. The same Cd treatment to male rats, however, resulted in a much more pronounced and prolonged reduction in AHH and APND activities, which was attributable to a Cd-induced testicular necrosis and, hence, impairment of androgen secretion. 5. Accordingly, Cd treatment to castrated male rats did not lower the enzyme activities any further, and full recovery of activities was obtained after the administration of testosterone. 6. Both GT and GST, the two sex-independent enzymes, were not significantly affected by either Cd or gonadectomy in the male rat. 7. The present data show that a low acute dose of Cd induces chemical castration without severely altering hepatic function.     

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.     

Cisplatin‐Induced Testicular Toxicity in Rats: The Protective Effect of Arjunolic Acid

In the present study, the effect of arjunolic acid on testicular damage induced by intraperitoneal injection of rats with 7 mg/kg cisplatin was studied. Cisplatin induced a significant reduction in testicular weights, plasma testosterone, and testicular reduced glutathione levels in addition to a significant elevation of testicular malondialdehyde levels and testicular gene expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor‐α (TNF‐α), and p38 mitogen‐activated protein kinase (MAPK) when compared with the control group (p < 0.05). Lower tubular diameters and depletion of germ cells and irregular small seminiferous tubules with Sertoli cells only were observed in the cisplatin group. Arjunolic acid administration significantly corrected the changes in both biochemical and histopathological parameters. Arjunolic acid plays a significant protective role against cisplatin‐induced testicular injury by attenuating oxidative stress parameters along with downregulation of iNOS, TNF‐α, and p38‐MAPK testicular expressions.     

Combined effects of cadmium and nickel on testicular xenobiotic metabolizing enzymes in rats

When male rats were given a single dose of cadmium (Cd) (3.58 mg CdCl₂·H₂O/kg, ip) 72 hr prior to sacrifice, the testicular 7-ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) activities toward the substrates 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (EAA), 1,2-epoxy-3-(p-nitrophenoxy)-propane (EPNP), and cumene hydroperoxide (CHPx) decreased significantly as compared to controls. Cd also inhibited reduced glutathione (GSH) level while increasing the lipid peroxidation (LP) level significantly. When the animals were given a single dose of nickel (Ni) (59.5 mg NiCl₂·6H₂O/kg, ip) 16 hr prior to sacrifice, significant decreases were observed in EROD and GST activities toward CDNB, EAA, EPNP, and CHPx, and GSH level. No significant alterations were noted in DCNB GST activity and LP level by Ni. For the combined treatment, rats received the single dose of Ni 56 hr after the single dose of Cd and were killed 16 hr later. In these animals, lesser depressions were observed on EROD activity and LP level than those of Cd alone. The combination of metals significantly inhibited GST activities and GSH level but not to a greater degree than noted by Cd or Ni alone. Plasma testosterone levels of Cd-, Ni-, and combination-treated rats decreased significantly compared to controls. The strongest depression was achieved by Cd alone. Cd, both alone and in combination with Ni, increased the tissue Ni uptake significantly. Ni, however, did not produce such an effect on the tissue uptake of Cd in either case. Cd treatment caused interstitial edema and coagulation necrosis in seminiferous tubules and also caused fibrinoidal necrosis in vascular endothelium. Ni treatment did not produce any pathological testicular alterations compared to controls. Combined treatment produced fewer pathological alterations (i.e., only interstitial edema) than that of Cd treatment. These results reveal that the combination of Cd and Ni does not have a synergistic effect on testicular xenobiotic metabolizing enzymes, and in contrast, Ni has an ameliorating effect on pathological disturbances caused by Cd alone in the rat testis.     

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.     

Effects of diallyl sulfide and zinc on testicular steroidogenesis in cadmium-treated male rats

Cadmium (Cd) is one of the environmental pollutants that affect various tissues and organs including testis. Harmful effect of cadmium on testis is known to be germ cell degeneration and impairment of testicular steroidogenesis. In the present study, the effect of diallyl sulfide (DAS), a sulfur-containing volatile compound present in garlic, and zinc (Zn) was investigated on cadmium-induced testicular toxicity in rats. Male adult Wistar rats treated with cadmium (2.5 mg/kg body wt, five times a week for 4 weeks) showed decreased body weight, paired testicular weight, relative testicular weight, serum testosterone, luteinizing hormone, follicle-stimulating hormone, and testicular total antioxidant capacity (TAC) and protein levels. Testicular steroidogenic enzymes, such as 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and marker enzymes, such as sorbitol dehydrogenase (SDH), lactate dehydrogenase (LDH), acid phosphatase (ACP), alkaline phosphatase (ALP), and glucose-6-phosphate dehydrogenase (G6PD), showed a significant decrease in activities whereas that of gamma-glutamyl transferase was significantly increased after cadmium exposure. The results have revealed that concurrent treatment with DAS or zinc restored key steroidogenic enzymes, SDH, LDH, and G6PD and increased testicular weight significantly. DAS restored the TAC level and increased testosterone level and relative testicular weight significantly. Zinc restored testicular protein level and body weight. It can be concluded that cadmium causes testicular toxicity and inhibits androgen production in adult male rats probably by affecting pituitary gonadotrophins and that concurrent administration of DAS or zinc provides protection against cadmium-induced testicular toxicity.