Testicular Superoxide Dismutase Activity Research Articles

Selenium and Omega-3 Fatty Acids Ameliorate Highly Active Anti-Retroviral Therapy (HAART)-induced Reproductive Impairment in Male Wistar Rats.

Highly active anti-retroviral therapy (HAART) is currently the main stay in the treatment of Human Immunodeficiency Virus (HIV) disease. This treatment regimen typically combines three or more antiretroviral drugs and like most drug combinations or polypharmacy, has side effects including those on reproductive function which could place HIV patients on HAART under double risk in terms of reproductive function. Part of tissue damage following HAART administration is blamed on oxidative stress. We therefore sought to explore effects of Omega 3 and Selenium, two common antioxidants on HAART-induced male reproductive impairment in a non-HIV animal model. Sixteen male adult Wistar rats weighing 120g to 250g used for the study were grouped into 4 groups of four rats each (control, HAART-only, HAART + Omega 3 and HAART + Selenium groups). Duration of daily administration was six weeks. Results showed no significant changes in pH of epidydimal semen among the groups. Sperm count and viability were significantly reduced in HAART-only compared with control (p<0.05) but increased in HAART + Omega 3 and HAART + Selenium groups compared with HAART-only group (p< 0.05). Sperm motility was significantly reduced in HAART-only compared with control group (p< 0.05). A significantly higher percentage of total sperm defects was observed in HAART-only group compared with control (p <0.05) but significantly lower in the HAART + Selenium compared with HAART-only groups (p<0.05). Serum testosterone was significantly reduced in HAART-only compared with control groups (p<0.05) but significantly increased in HAART + Omega 3 and HAART + Selenium groups compared with HAART- only group (p<0.05). Serum concentration of luteinizing and follicle stimulating hormones were not significantly different among the groups. Testicular concentration of malondialdehyde was significantly increased in HAART-only compared with control (p<0.05) but significantly reduced in HAART + Omega 3 and HAART + Selenium groups compared with HAART-only group (p<0.05 in each). Testicular glutathione peroxidase activity was significantly reduced in HAART-only and HAART + Selenium groups compared with control (p< 0.05), but significantly higher in HAART + Omega 3 and HAART + Selenium compared with HAART-only groups (p<0.05 each). Testicular superoxide dismutase activity was significantly lower in the HAART-only and HAART + Selenium compared with control (p<0.05) but significantly higher in HAART + Omega 3 and HAART + Selenium compared with HAART-only groups (p<0.05 each). Level of tumour necrosis factor - alpha in testes was significantly higher in HAART-only (p<0.05) but lower in the HAART + Selenium (p<0.05) groups compared with control. Tumor necrosis factor-alpha was however significantly reduced in HAART + Omega 3 and HAART + Selenium groups compared with HAART-only (p<0.05 each) groups. Interleukin-6 levels were significantly increased in all HAART-administered groups compared with control (p<0.05 each) though significantly reduced in HAART + Omega 3 and HAART + Selenium compared with HAART-only groups (p<0.05 each). In conclusion, co-administration of Omega 3 or Selenium with HAART ameliorates HAART-induced male reproductive impairment, alteration in redox and inflammatory status in rats. Keywords: HAART, male reproductive impairment, Omega 3, Selenium.

Protective role of naftidrofuryl against methotrexate-induced testicular damage via the amelioration of the p53/miRNA-29a/CDC42 apoptotic pathway, inflammation, and oxidative stress

This study aimed to assess the possible protective effects of naftidrofuryl (Naf) against methotrexate (MTX)-induced testicular toxicity in rats. Male rats were randomly distributed into four groups: control, Naf, MTX, and MTX+Naf groups. MTX administration induced oxidative stress, inflammation, and apoptosis in the testicular tissue, while pretreatment with Naf attenuated these pathways. Naf pretreatment significantly decreased malondialdehyde and interleukin-6 contents, microRNA-29a (miRNA-29a) expression level, and nuclear factor kappa B and p53 immunostaining in the testicular tissues compared to the MTX group. Conversely, it significantly increased Johnsen's score, serum testosterone level, serum total antioxidant capacity, testicular superoxide dismutase activity, testicular catalase activity, and testicular cell division cycle 42 (CDC42) expression compared to the MTX group. In conclusion, Naf exerted a significant protective effect against MTX-induced testicular toxicity via antioxidant and anti-inflammatory mechanisms and modulating the p53/miRNA-29a/CDC42 apoptotic pathway.

Beneficial effects of combination therapy with testosterone and hydrogen sulfide by reducing oxidative stress and apoptosis: Rat experimental varicocele model.

Despite the effectiveness of testosterone therapy in conditions associated with testosterone deficiency, including varicocele, several dose-dependent side effects limit the clinical use of testosterone therapy. Hydrogen sulfide, a toxic gas in high concentrations but a beneficial molecule in low concentrations, acts as both a major effector and an important inducer of testosterone. This study investigated whether a subeffective dose of testosterone combined with a subeffective dose of hydrogen sulfide donor sodium hydrosulfide (NaHS) can be effective in an experimental varicocele model through a possible additive effect. Thirty Wistar rats weighing 200-250 gr were divided into 5 groups as (n = 6/each): sham, varicocele, testosterone (200 µg/kg, 5 times per wk for 4 consecutive weeks), NaHS (15 μmol/L, daily for 4 consecutive wk) and testosterone + NaHS (200 µg/kg, 5 times per wk + 15 μmol/L, daily, both for 4 consecutive wk). All animals, except in the sham group, underwent varicocele induction. The coadministration of testosterone and NaHS significantly increased serum testosterone (10.23 0.95, p = 0.01), testicular H2S levels (608.94 21.09, p 0.001), and testicular superoxide dismutase activity (66.14 1.56, p 0.001), decreased malondialdehyde levels (0.77 0.52, p 0.001), and B-cell lymphoma 2-associated X protein to B-cell lymphoma 2 (0.16 0.01, p 0.001) protein expression ratio in the testicular tissues and improved sperm parameters and testicular histopathology compared to the varicocele group. The combination therapy of subeffective doses of testosterone and NaHS can attenuate the varicocele-induced damages by reducing testicular oxidative stress and apoptosis and thus can be considered an effective approach with fewer side effects.

Achillea millefolium alleviates testicular damage in paclitaxel-intoxicated rats via attenuation of testicular oxido-inflammatory stress and apoptotic responses.

The aim of this study was to investigate the effects of Achillea millefolium extract in paclitaxel-induced testicular toxicity in rats. The groups were designed as (1) control, (2) paclitaxel (8mg/kg, intraperitoneally), (3) paclitaxel (8mg/kg, intraperitoneally) + Achillea millefolium (200mg/kg, orally for 14 consecutive days) and (4) paclitaxel (8mg/kg, intraperitoneally) + Achillea millefolium (400mg/kg, orally for 14 consecutive days). Serum levels of testosterone, luteinising hormone and follicle-stimulating hormone, as well as total antioxidant capacity and total oxidant status were measured one day after receiving the last dose of Achillea millefolium extract. Testicular superoxide dismutase activity, malondialdehyde, tumour necrosis factor alpha and interleukin-1β levels, the expressions of nuclear factor kappa B and caspase-3 were evaluated. In addition, testicular sections were evaluated histopathologically and 8-hydroxy-2'-deoxyguanosine was detected immunohistochemically. Achillea millefolium improved the levels of luteinising hormone, follicle-stimulating hormone and testosterone, upregulated testicular antioxidant enzymes and downregulated inflammation. Furthermore, we observed that Achillea millefolium restored testicular histopathological structure and significantly suppressed oxidative DNA damage and apoptosis by reducing the expression of caspase-3. Taken together, our results suggest that Achillea millefolium has protective effects against paclitaxel-induced testicular toxicity and is a promising natural product with the potential to improve male fertility.

Puerarin prevents cadmium-induced disorder of testicular lactic acid metabolism in rats by activating 5' AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signaling pathway.

Cadmium (Cd) interferes with the function of the male reproductive system; however, the molecular mechanism is poorly understood. This study aimed to evaluate the effect of puerarin (PU) on Cd-induced testicular lactic acid metabolism disorder. Weaning male Sprague-Dawley rats were pre-fed for 7 days, weighed, and randomly divided into four groups: Control group, CdAc2 group, CdAc2 + PU group, PU group. The results showed that Cd accumulated in the testis, the testicles became congested and shrank, and the testis index decreased in the rats treated in the CdAc2 group. Cadmium exposure reduced the serum concentration of testosterone, and the concentration of lactic acid and pyruvate in the testis. Cd decreased testicular superoxide dismutase activity and total antioxidant capacity, and increased testicular malondialdehyde levels. Cd reduced the level of ATP, glycolytic gene expression, and lactate production-related proteins in the testis. Cd also decreased the expression of 5' AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signaling pathway-related proteins in the testis. However, these negative effects were attenuated by PU administration. In summary, Cd reduces the production of lactic acid in the testis of rats, while PU administration restores the production of lactic acid and reduces the toxicity of Cd to the testis of rats.

Effects of Cultured Cordycep militaris on Sexual Performance and Erectile Function in Streptozotocin-Induced Diabetic Male Rats.

Cordyceps militaris (CM), a valuable edible and medicinal fungus, has been used as traditional medicine to treat health conditions, as well as hyposexuality in Asian societies for over a century. Due to the high demand, several artificial cultivation methods have been developed for their biological activities. In this study, CM was cultured on medium that contained white rice and silkworm pupae, and the levels of cordycepin and adenosine, as well as its aphrodisiac effects in diabetes-induced erectile dysfunction (DIED), were evaluated. Diabetic rats were induced by streptozotocin (STZ) injection and administered orally with CM (0.1, 0.5, and 1.0 g/kg BW/day) for 3 weeks. Diabetic rats in negative and positive control groups received vehicle and sildenafil citrate (5 mg/kg), respectively. Results showed the changes in mating behaviour in which mount latency and intromission latency were significantly increased in diabetic rats, compared with the normal control group. Diabetic rats also showed a significant reduction in intracavernosal pressure (ICP) response to cavernous nerve stimulation, sperm count, testosterone level, penile nitric oxide synthase (NOS), and testicular superoxide dismutase (SOD) activities, when compared to the normal control group. Administration of CM (0.1, 0.5, and 1.0 g/kg BW/day) reversed the effects of diabetes on the mating behaviour, and the ICP responses to electrical stimulation. Moreover, the levels of penile NOS, testicular SOD activities, testosterone, and sperm count were significantly increased, and testicular malondialdehyde (MDA) levels were significantly decreased in these treated diabetic rats. Diabetic rats treated with sildenafil showed a significant induction in intromission frequency and NOS and SOD activities, as well as a marked increase in ICP responses. These results suggest that CCM exerts its aphrodisiac effect, possibly through activating testosterone production and suppressing oxidative stress to enhance erectile function in diabetic rats.

Uranium exposure increases spermatocytes metaphase apoptosis in rats: inhibitory effect of thymoquinone and N-acetylcysteine.

Uranyl acetate (UA), a commercial stock from depleted uranium (DU), has a combined effect of chemical toxicity and mild radioactivity. Here, we investigated the potential antioxidant, antiapoptotic and cytoprotective effects of thymoquinone (TQ) and N-acetylcysteine (NAC) against UA-induced testicular damage in rats. UA reduced testicular superoxide dismutase (SOD) activity and nitric oxide (NO) and glutathione (GSH) levels relative to the control group. Interestingly, the testicular SOD activity and NO and GSH levels of UA/TQ- and UA/NAC-treated groups were also significantly lower relative to the control. A marked increase in spermatocytes metaphase apoptosis was found (stage XIII) in UA-treated rats, which is probably due to difficulties in segregation of homologous-chromosomes. This may clarify why UA exposure decreased round spermatids numbers and fertility in previous studies. To check the reason of partial metaphase arrest, the presence of DNA-damage-related γ-H2AX foci in late spermatocytes of all groups was checked, but only insignificant increase was found in UA-treated group. TQ or NAC supplementation reduced the apoptosis and improved the testicular histological alterations. Thus, TQ and NAC attenuate UA adverse effects on the testicular microenvironement through anti-apoptotic and cytoprotective but not antioxidant effects.

Attenuating Effect of N-Acetylcysteine onApoptosis Associated with ImidaclopridInduced Testicular Damage inMale Albino Rats

N-acetylcysteine (NAC), as a nutritional supplement, is a greatly applied antioxidant invivo and in vitro. NAC is a precursor of L-cysteine that results in glutathione elevation biosynthesis.The therapeutic potential ofN-acetylcysteine (NAC) has been investigated as a bioprotective agent against oxidative stress and ischemic injury. Also, it is used as a treatment for certain mental and physical illnesses.The aim of this study was to evaluate the protective and attenuatingapoptosis effect ofNACon imidaclopride (IMI) induced testicular damage in rats. Forty male albino rats wereclassified randomly into four equal groups. Group1 (control). Group2 (IMI): rats receivedIMIorally day after day over a period of 8 weeks at a dose level of 21.2mg/kg b.w (1/20 LD50). Group3 (NAC):rats received NAC(200 mg/kg body weight) orally for8 weeks.Group 4 (NAC+IMI): rats received NAC(200 mg/kg body weight) orally for 4 daysbefore and along with the administration of (IMI) over a period of 8 weeks.At the end of the experiment testes were isolated for the determination of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced Glutathione (GSH) and comet assay. Also, for histopathological examination. The obtained results showed a significant increase in testicular tissue MDA, andDNA damage detected by comet assay in imidaclopride intoxicated rats. However, Testicular SOD activity, catalase, and GSH concentration were markedly decreased. Histopathological alteration caused by IMI toxicity were presented by slightly thickened tunica albuginea with less congestion of sub-capsular blood vessels,mild degeneration of the germinal epithelium of some seminiferous tubules with mild interstitial edema. NACprotection to IMI induced testicular damage in rats caused a significant improvement of all previous parameters and attenuate the histopathological changes. These results suggested that, NAC treatment exerts a protective effect on testicular damage by improving ofoxidative stress markers and DNA damage detected by comet assayin rats through free radical scavenging and anti-inflammatory activities as well as regenerating endogenous antioxidant defense system mechanisms.

WITHDRAWN: Protocatechualdehyde improves antineoplastic cyclophosphamide-induced mouse testicular damage

// Chun-Na An 1 , Xiao-Ping Pu 2 , Qiu-Ping Yang 3 , Jing-Ting Dong 3 , Shu-Ying Han 1 , Rui Wei 1 and Hong-Ning Zhang 4 1 Department of Pharmacology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, China 2 Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, China 3 Jitang College, North China University of Science and Technology, Tangshan, China 4 Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China Correspondence to: Hong-Ning Zhang, email: zhang_hn2008@126.com Keywords: protocatechualdehyde; cyclophosphamide; testicular damage; DJ-1 Received: July 21, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: November 28, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Epub: January 02, 2018 ABSTRACT We studied the effects of protocatechualdehyde on mouse sperm survival and sperm membrane integrity in vitro and on cyclophosphamide-induced mouse testicular damage in vivo . Protocatechualdehyde (0.01, 0.1, and 1 mg/mL) improved sperm survival rate and sperm membrane integrity in separated mouse sperm (all P &lt; .05). In cyclophosphamide-treated male mice (60 mg/kg/d by intraperitoneal injection, 5 days of treatment), protocatechualdehyde (40 mg/kg/d by intragastric gavage, 35 days of treatment) increased the testis index, epididymis index, and sperm nuclear maturity (all P &lt; .05). Protocatechualdehyde also improved testis morphology characterized by orderly arranged layers of spermatogenic cells, numbers of sperm in the lumen, normal mesenchymal cells, and close and tidy arrangement of the seminiferous tubules. Protocatechualdehyde also increased testicular superoxide dismutase activity and elevated DJ-1 expression. In addition, it decreased expression of ICAM-1 and enhanced the expression of VCAM-1, PEDF, VEGF, and PPAR&gamma;. These findings indicate that protocatechualdehyde increases mouse sperm survival and sperm membrane integrity in vitro and reduces cyclophosphamide-induced mouse testicular damage via DJ-1 and other targets in vivo . Protocatechualdehyde may thus be useful for treating reproductive damage and antineoplastic cyclophosphamide-induced reproductive toxicity.

Modulatory Effects of Lycopene and Ellagic Acid on Reproductive Dysfunction Induced by Polychlorinated Biphenyl (Aroclor 1254) in Male Rats

The present study was conducted to investigate the possible protective effects of lycopene (LP) and ellagic acid (EA) on aroclor (AR) 1254-induced testicular and spermatozoal toxicity associated with the oxidative stress and apoptosis in male rats. The control group was treated with placebo. LP (10 mg/kg/every other day), EA (2 mg/kg/every other day) and AR (2 mg/kg/day) groups were given alone LP, EA and AR respectively. One of the last two groups received AR + LP, and the other treated with AR + EA. Body and reproductive organ weights, epididymal sperm characteristics, testicular tissue lipid peroxidation levels, antioxidant enzyme activities, histopathological changes and apoptosis via Bax and Bcl-2 genes were investigated. AR administration caused statistically significant decreases in body-weight, epididymal sperm concentration, testicular superoxide dismutase activity, diameters of seminiferous tubules, germinal cell layer thickness and Johnsen's testicular score, and increases in relative weights of testis, epidydimis and seminal vesicles, rates of abnormal sperm and apoptotic cell expression along with degeneration, desquamation and disorganization in spermatogenic cells, and interstitial oedema and congestion in testicular tissue. LP and EA treatments to AR-treated rats markedly decreased abnormal sperm rates, testicular thiobarbituric acid reactive substances level, and increased the glutathione (GSH) level, GSH-peroxidase, catalase activities and epidiymal sperm concentration as compared with the alone AR group. Additionally, the AR-induced histopathological damages were totally or partially recovered by LP or EA administrations respectively. AR damages the testicular tissue and spermatozoa by impairing the oxidant/antioxidant balance and by increasing the apoptotic spermatogenic cell rates. However, both LP and EA have modulator effects on AR-induced reproductive dysfunction in male rats.

Changes in the Plasma Testosterone Level and Testicular Superoxide Dismutase Activity of 5 Azoospermic Beagles after GnRH Analogue Injections

The peripheral blood plasma testosterone (T) levels and superoxide dismutase (SOD) activity were measured in 5 azoospermic (AZ-) beagles. The mean values in the AZ-dogs were significantly lower than in 7 control beagles (P<0.001). Subcutaneous injections of 1 mug/kg GnRH analogue three times weekly in the AZ-dogs induced significant increases in mean T level and SOD activity (P<0.05) and improvement in spermatogenesis. Thus, spermatogenic function in the dog appears to be maintained by T and normal SOD activity in the testis.

Comprehensive assessment of the effect of Sphenocentrum jollyanum root extract on male reproductive activity in albino rats.

Aim: To evaluate the effect of methanol extract from the Sphenocentrum jollyanum root on male reproductive activity. Methods: Male albino rats were treated orally with distilled water (vehicle for the extract; control) and 50, 100 and 150 mgkg-1 body weight of Sphenocentrum jollyanum root extract for 8weeks. Each group had its own recovery. Rats were killed 24h after the last treatment. Caudal epididymal sperm count, motility, viability, morphology and organ weights were determined. Hematological indices, serum proteins, enzymes, testicular superoxide dismutase (SOD) activity, and testicular and epididymal histology were determined. Results: Compared with the control, the extract caused a dose dependent significant (P<0.05) reduction in progressive motility of spermatozoa, viability and total sperm counts. The number of abnormal spermatozoa and epididymal volume were not statistically significant. There was a significant increase (P<0.05) in serum testosterone levels in rats treated with 50 (P<0.01) and 100mgkg-1 (P<0.05) of Sphenocentrum jollyanum. There was a significant (P<0.05) increase in red blood cell count, packed cell volume and hemoglobin concentration, whereas there was no change in white blood cell count, mean total serum protein, albumin and globulin in the sera of Sphenocentrum jollyanum treated rats when compared with the control. The extract caused a significant decrease (P<0.05) in serum aspartate and alanine aminotransferase activities with a significant increase (P<0.05) in testicular SOD activity at a dose of 50mgkg-1 bodyweight. Testicular cytoarchitecture of the extract treated rats showed degeneration of seminiferous tubules, whereas regeneration of germinal epithelium and restructuring of the germinal interstitium occurred in the recovery rats. No lesions were observed in the epididymis of the rats. Conclusion: The results suggest that methanol extract of the Sphenocentrum jollyanum root could produce harmful effects on reproductive functions in male albino rats which can be attributed to poor sperm quantity (epididymal sperm count), quality (sperm motility, viability and morphology) and testicular degeneration. The steroidogenic potential of the plant could explain its use as an aphrodisiac agent. (Reprod Med Biol 2006; 5: 283-292).

Lipid peroxidation and antioxidant enzyme activities in the rat testis after cigarette smoke inhalation or administration of polychlorinated biphenyls or polychlorinated naphthalenes.

Lipid peroxidation products and antioxidant enzyme activities were studied in the rat testis following exposures to cigarette smoke, polychlorinated biphenyls (PCBs), or polychlorinated naphthalenes (PCNs). Three hours after a single 1-hour period of smoke inhalation, the levels of fluorescent chromolipids and thiobarbituric acid-reactive species (TBARS) were markedly increased in the testis (+49%, P < 0.01, and +43%, P < 0.05, respectively). Twelve hours after daily smoking for 1 hour, for 1, 5, or 10 days, such an increase was not found. Activities of the antioxidant enzymes superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), glutathione transferase (GSH-Tr), or hexose monophosphate shunt (HMS) were not affected immediately, 3 hours, or 12 hours after a single smoking session. Twelve hours after smoking for 5 days, the activity of catalase was decreased (-16%, P < 0.05). Smoking exposures had no consistent effects on serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), or testosterone concentrations. Single i.p. injections of PCB or PCN mixtures resulted in decreases in testicular SOD activity 1 day after the exposures (-14%, P < 0.05, and -51%, P < 0.01, respectively). Catalase activity also decreased after both exposures (-30 to -42%, P < 0.05, at days 1-7 after PCB exposure, and -37 to -43%, P < 0.05, at days 3-7 after PCN exposure). Ninety days after the PCN exposure, activities of GSH-Px and GSH-Tr were decreased in the testis (-20%, P < 0.05, and -26%, P < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)