NF-κB-Associated Redox Signaling and Intrinsic Apoptotic Activation in Polystyrene Nanoplastic–Induced Testicular Toxicity and Modulatory Effects of Nelumbo nucifera

Testicular damage is one of the most deleterious effects whenever cisplatin (CIS) is employed in cancer chemotherapy. Oxidative stress has been proven to be involved in CIS induced toxicity. Thus, the current study explored the possible protective effect of L-carnitine (L-CAR) against cisplatin-induced testicular damage in rats. L-carnitine (500 mg/kg/day; i.p.) was injected for 15 days, whereas cisplatin (10 mg/kg; i.p.) was injected as a single dose at the 12th day to induce testicular damage in adult male Sprague-Dawley rats. In the current study, CIS reduced the reproductive organs weight, sperm count, sperm motility and serum testosterone level beside a marked increase in the incidence of sperm abnormalities. In addition, it significantly increased malondialdehyde (MDA) and nitric oxide (NO) along with a marked decrease in testis reduced glutathione (GSH) content and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. At the same time, CIS administration resulted in marked elevation in tumor necrosis factor-α (TNF-α) production and nuclear factor-kabba B (NF-κB) expression. These results were confirmed by histopathological examination. Treatment with L-CAR markedly attenuated cisplatin-induced injury by suppression of oxidative/nitrosative stress and inflammation, amendment of antioxidant defenses, as well as improvement of steroidogenesis, spermatogenesis and testicular histological features. This study suggests a novel therapeutic application for L-carnitine as a protective agent against cisplatin-induced testicular toxicity through its promising anti-inflammatory and antioxidant capacities.

The protective effect of quercetin on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced testicular damage in rats was investigated. Twenty-two rats were equally divided into four groups; first group was kept as control and given corn oil as carrier. In second group, TCDD was orally administered at the dose of 2 μ (kg week)(-1) for 60 days. In third group, quercetin was orally administered at the dose of 20 mg (kg day)(-1) by gavages, and in fourth group TCDD and quercetin were given together at the same doses. Although TCDD increased the formation of thiobarbituric acid reactive substances (TBARS) significantly, it caused a significant decline in the levels of glutathione (GSH), catalase (CAT), GSH-Px and CuZn-Superoxide Dismutase (CuZn-SOD) in rats. In contrast, quercetin significantly increased the GSH, CAT, GSH-Px and CuZn-SOD levels but decreased the formation of TBARS. In addition, sperm motility, sperm concentration and serum testosterone levels were significantly decreased but abnormal sperm rate and testicular damage were increased with TCDD treatment. However, these effects of TCDD on sperm parameters, histological changes and hormone levels were eliminated by quercetin treatment. Our results show that administration of TCDD induces testicular damage (oxidative stress, testes tissue damage, serum hormone level and sperm parameters), and quercetin prevents TCDD-induced testicular damage in rats. Thus, quercetin may be useful for the prevention and treatment of TCDD-induced testicular damage.

Objective: To investigate the effects of folic acid on testicular oxidative damage in sodium fluoride-induced male Wistar rats. Methods: A total of 24 male Wistar rats were divided into 4 groups: the control, sodium fluoride (fed with 100 mg/L sodium fluoride through drinking water orally for 21 days), folic acid (36 μg/kg body weight/day, orally), and sodium fluoride plus folic acid (received similar dose orally) groups. At the end of 21 days, epididymal sperm parameters, biochemical analysis of testicular tissue, and serum hormonal levels were performed along with histopathological studies. Results: Sodium fluoride intoxication resulted in marked reduction in gonado somatic index, serum luteinizing hormone, and testosterone level along with 3 β -hydroxysteroid dehydrogenase and 17 β -hydroxysteroid dehydrogenase activities. In addition, reduction in sperm density, as well as loss of sperm motility and sperm viability, were also observed. Besides, increased levels of testicular malondialdehyde, nitrite, interleukin-6 and tumor necrosis factor- α as well as decreased levels of superoxide dismutase and catalase activities and reduced glutathione content were found to be associated with this toxicity. Folic acid co-treatment, on the other hand, could prevent all the sodium fluoride-induced testicular pathophysiology and oxidative stress related parameters. Histological examinations of testicular sections from the experimental rats supported these results. Conclusions: Combining all, this study suggests that being an antioxidant, folic acid plays a beneficial role against fluoride-induced adverse effects on the male reproductive system.

Diosgenin ameliorates testicular damage in streptozotocin-diabetic rats through attenuation of apoptosis, oxidative stress, and inflammation

Protective effect of magnesium oxide nanoparticles against experimental varicocele-induced testicular damage in rats.

The present study was carried out to evaluate the ameliorative effects of kolaviron (a biflavonoid from the seeds of Garcinia kola) and curcumin (from the rhizome, Curcuma longa L.) on the di-n-butylphthalate (DBP)-induced testicular damage in rats. Administration of DBP to rats at a dose of 2 g/kg for 9 days significantly decreased the relative testicular weights compared to the controls, while the weights of other organs remained unaffected. Curcumin or kolaviron did not affect all the organ weights of the animals. While only DBP treatment significantly increased the testicular malondialdehyde level and gamma-glutamyl transferase activity (gamma-GT), it markedly decreased glutathione level, the testicular catalase, glucose-6-phosphate dehydrogenase, superoxide dismutase, sperm gamma-GT activities and serum testosterone level compared to the control group. Data on cauda epididymal sperm count and live/dead ratio were not significantly affected in the DBP-treated rats. Alone, DBP treatment resulted in a 66% decrease in spermatozoa motility and a 77% increase in abnormal spermatozoa in comparison to control. DBP-treated rats showed marked degeneration of the seminiferous tubules with necrosis and defoliation of spermatocytes. The DBP-induced injuries in biochemical, spermatological parameters and histological structure of testis were recovered by treatment with kolaviron or curcumin. The pattern in the behaviour of these compounds might be correlated with their structural variations. Our results indicate that kolaviron and curcumin protect against testicular oxidative damage induced by DBP. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties and as such may prove useful in combating phthalate-induced reproductive toxicity.

Simple SummaryThe chemotherapeutic agent Cisplatin (Cis) has testicular damage as a side effect. Therefore, efforts are being done by scientists to get over this effect. The current experiment was done to utilize bone marrow-derived stem cells (BM-MSCs) and beetroot extract (BRE) in reducing the Cis testicular damage in rats. In the current study, Cis reduced the sperm count, plasma testosterone level, the testicular activity of alkaline phosphatase beside a marked inhabitation of succinate dehydrogenase activity. Also, it significantly increased malondialdehyde and along with a marked decrease in testis reduced glutathione content and total antioxidant capacity. At the same time, Cis administration resulted in a marked elevation in interleukine-6 and the iNOS and caspase-3 genes, however it decreased the expression of steroidogenic acute regulatory protein (StAR). Stem cell therapy (BM-MSCs) was accompanied with the use of herbal therapy (BRE) resulted in great improvement of all previous parameters. These results were confirmed by histopathological and immunohistochemical examination. In conclusion the current study recommends the use of beetroot as natural food in combination with stem cell therapy for the patient suffering from the testicular side effect of cisplatin chemotherapy.Cisplatin (Cis) a drug commonly used as a chemotherapeutic agent to treat various types of cancer, inducing testicular damage. The present study aimed to investigate the inhibitory potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) and beetroot extract (BRE) in albino rats after testicular toxicity induced by cisplatin. Thirty adult male albino rats were grouped into: the control group, Cis group receiving a single dose of 7 mg/kg i.p. (intraperitoneal) to induce testicular toxicity, Cis plus BM-MSCs injected Cis followed by 2 × 106 of BM-MSCs; Cis plus BRE group receiving Cis followed by 300 mg/kg body weight/day of BRE, and Cis plus BM-MSCs and BRE group. In the current study, Cis reduced sperm count, serum testosterone level, and testicular activity of alkaline phosphatase (AKP), besides a marked inhibition of succinate dehydrogenase (SDH) activity. In addition, it significantly increased malondialdehyde (MDA) and along with a marked decrease in testis reduced glutathione content and total antioxidant capacity (TAC). At the same time, Cis administration resulted in a marked elevation in interleukine-6 and the iNOS and caspase-3 genes; however, it decreased the expression of steroidogenic acute regulatory protein (StAR). Combined treatment with BM-MSCs and BRE resulted in great improvement of all previous parameters. These results were also confirmed by histopathological and immunohistochemical examination. In conclusion, both MSCs and BRE were found to have potent potentials to inhibit testicular damage induced by cisplatin.

Transcriptome and proteome analyses reveal the mechanisms involved in polystyrene nanoplastics disrupt spermatogenesis in mice

To explore the mechanism underlying the inhibitory effect of quercetin against testicular oxidative damage induced by a mixture of 3 commonly used phthalates (MPEs) in rats. Forty male Sprague-Dawley rats were randomly divided into control group, MPEs exposure group, and MPEs with low-, median- and high-dose quercetin treatment groups. For MPEs exposure, the rats were subjected to intragastric administration of MPEs at the daily dose of 900 mg/kg for 30 consecutive days; Quercetin treatments were administered in the same manner at the daily dose of 10, 30, and 90 mg/kg. After the treatments, serum levels of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), and testicular malondialdeyhde (MDA), catalase (CAT) and superoxide dismutase (SOD) were detected, and testicular pathologies of the rats were observed with HE staining. The expressions of nuclear factor-E2-related factor 2 (Nrf2), Kelch-like ECH2 associated protein 1 (Keap1) and heme oxygenase 1 (HO-1) in the testis were detected using immunofluorescence assay and Western blotting. Compared with the control group, the rats with MPEs exposure showed significant reductions of the anogenital distance, weight of the testis and epididymis, and the coefficients of the testis and epididymis with lowered serum testosterone, LH and FSH levels (P < 0.05). Testicular histological examination revealed atrophy of the seminiferous tubules, spermatogenic arrest, and hyperplasia of the Leydig cells in MPEs-exposed rats. MPEs exposure also caused significant increments of testicular Nrf2, MDA, SOD, CAT and HO-1 expressions and lowered testicular Keap1 expression (P < 0.05). Treatment with quercetin at the median and high doses significantly ameliorated the pathological changes induced by MPEs exposure (P < 0.05). Quercetin treatment inhibits MPEs-induced oxidative testicular damage in rats possibly by direct scavenging of free radicals to lower testicular oxidative stress and restore the regulation of the Nrf2 signaling pathway.

Cigarette smoke (CS) can cause testicular damage and we investigated the possible protective effect of honey against CS-induced testicular damage and oxidative stress in rats. CS exposure (8 min, 3 times daily) and honey supplementation (1.2 g/kg daily) were given for 13 weeks. Rats exposed to CS significantly had smaller seminiferous tubules diameter and epithelial height, lower Leydig cell count and increased percentage of tubules with germ cell loss. CS also produced increased lipid peroxidation (TBARS) and glutathione peroxidase (GPx) activity, as well as reduced total antioxidant status (TAS) and activities of superoxide dismutase (SOD) and catalase (CAT). However, supplementation of honey significantly reduced histological changes and TBARS level, increased TAS level, as well as significantly restored activities of GPx, SOD and CAT in rat testis. These findings may suggest that honey has a protective effect against damage and oxidative stress induced by CS in rat testis.

Objective: Investigating the effect of green tea extract (GTE) on the testicular damage induced by cadmium chloride CdCl2 in male rats. Design: Randomized controlled study. Animals: 40 male Wistar rats. Procedures: Rats were randomly divided into four groups: A) control group (each rat daily received pellet diet); B) GTE group each rat daily received pellet diet as well as 3 ml of 1.5 % w/v GTE, C) CdCl2 group each rat was I/P injected a single dose of 1 mg/kg CdCl2, then daily received pellet diet, and D) CdCl2+GTE group each rat was I/P injected a single dose of 1 mg/kg CdCl2 then daily received pellet diet as well as 3 ml of 1.5 % w/v GTE. After 30 days, blood samples were collected for hormonal assays (testosterone, FSH, and LH). In addition, both testes were collected; one of them was used for quantification of 17-beta hydroxysteroid dehydrogenase III (17β-HSDIII) gene expression using a real-time PCR. The other testis was used for determination of catalase and reduced glutathione; GSH, Nitric oxide (NO) and malondialdehyde (MDA) levels. Results: CdCl2 decreased serum testosterone levels and its synthesis pathway (17β-HSDIII testicular gene expression). While antioxidants catalase and GSH were reduced, oxidants MDA were enriched in the testes of CdCl2-poisoned rats. This CdCl2-promoted testicular dysfunction was corrected via the administration of GTE to male rats. Conclusion and clinical relevance: GTE could be used as a remedy for protecting against CdCl2-induced testicular damage in male rats.

BackgroundEnergy drinks prevent fatigue and increase physical and cognitive performance; however, they also inflict toxic effects on the body. Blueberry (BB) possesses antioxidant and anti-inflammatory properties. The present study aimed to assess the possible the therapeutic effects of BB on testicular damage in adult male Wistar albino rats induced by administering the energy drink Code Red.ResultsThirty adult rats were used in the study, divided into five groups; Group 1 (Control), where rats were fed on distilled water and basal rodent diet only. The other four groups received different energy drink Code Red doses for 8 weeks and BB supplementation for another 6 weeks. Administration of low and high doses of Code Red induced a decline in serum levels of testosterone and antioxidant enzymes like superoxide dismutase (SOD), and glutathione (GSH), while malondialdehyde (MDA) was significantly increased relative to controls. A low dose of Code Red led to sporadic and scattered appearance of seminiferous tubules with loss of spermatogenic germ cells and marked degeneration of interstitial cells. A high dose of Cod Red exhibited increased degenerative changes in the tubules with highly congested thick vessels in the interstitial tissue. Also, testis from rats consuming either low or high doses of Code Red showed increased caspase-3 immunostaining in seminiferous tubules with early degeneration features. However, the deleterious effect of the administration of Code Red was remarkably ameliorated with the supplementation of BB. A reversal in the mutilative effect of Code Red was observed where with BB supplementation, the histopathology of the testis displayed recovery of most of the seminiferous tubules to normal structure. BB administration in both groups also showed negative or mild immunostaining for caspase-3.ConclusionsOral exposure of rats to Code Red produced noticeable testicular damage, especially in high doses, probably due to increased oxidative stress and inflammation. Blueberry administration exhibited therapeutic effects through its anti-inflammatory and antioxidative properties.

ABSTRACTFenvalerate (FEN), a pyrethroid insecticide used worldwide, has been shown to produce a potentially adverse effect on male reproduction. However the mechanisms are not completely understood. Thus this study aimed to (1) determine whether cellular apoptosis was involved in FEN-induced testicular damage in rats, and (2) identify the potential mechanism involved in FEN-induced apoptosis in testes. Data demonstrated that FEN markedly decreased serum testosterone levels, increased the inner diameter of seminiferous tubules, decreased the layers of spermatogenic cells, disturbed spermatogenesis and increased the number of apoptotic cells. Further, bioinformatic analysis of gene microarray in rat testis tissue showed that FEN significantly altered the expressions of genes (Krt8, Mal, Cd24, Lcn2, Phlda1, Arg2) related to apoptotic related processes. The expression pattern of these 6 genes was upregulated in FEN-treated rat testicular tissue. qRT-PCR analysis demonstrated that Phlda1, a well-documented pro-apoptotic factor, was significantly elevated by FEN. The expression of PHLDA1 testicular protein was also elevated following FEN exposure. In conclusion, our results suggest that FEN exposure induced deleterious effects on rat testes associated with Phlda1-mediated apoptosis which may act as a molecular mechanism underlying FEN induced rat testicular damage.

Summary The aim of this study was to investigate if lycopene could diminish the adverse effects of aflatoxin B1 (AFB1) on sperm characteristics, the testes, epididymis and oxidative stress in rats. A total of 28 adult male Wistar-Albino rats (8 weeks old weighing 180-220 g) were divided into four groups; Controls, lycopene treated rats (10 mg/kg BW, daily by gavage), AFB1 treated rats (2.5 mg/kg BW, single dose intra peritonal) and lycopene (10 mg/kg BW, daily by gavage) + AFB1 (2.5 mg/kg BW, single dose intra peritonal) treated rats. Traits of reproductive organs (testes and sperm characteristics, testicular histological findings and the testicular tissue oxidative status) were determined after 15 days of treatment. The sperm motility was significantly decreased while the rate of total abnormal sperms was significantly increased in rats treated with AFB1 alone compared to their levels in controls (P<0.001). The level of testes malondialdehyde (MDA) in rats treated with AFB1 was significantly higher than its level in controls (P<0.001). Treatment with AFB1 significantly decreased testes diameter and seminifer epithelium thickness (P<0.0001) when compared with the others. Similarly, the thickness of the germinative cell layer at seminifer tubul (ST) in rats treated with AFB1 was significantly smaller than controls. Treatment with lycopene significantly increased sperm motility (P<0.001) and alleviated the many negative effects of AFB1 on sperm characteristic and testicular damage in rats. In conclusion our results showed that consumption of 10 mg of lycopene/ BW given by gavage protected the rats to the toxicity of AFB1 when it is administrated as a single dose intraperitoneally.

PurposeTo investigate the effects of all-trans retinoic acid (ATRA) in cisplatin (CP)-induced testicular damage in rats.Materials and MethodsTwenty-eight male Wistar rats were divided into four groups: Control, ATRA alone, ATRA+CP, and CP alone. Body weight, testicular weight, sperm count, sperm motility, percentage of abnormal sperm, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) in testicular tissue, and testicular histopathology were compared among groups.ResultsThe sperm count and motility significantly decreased and the percentage of abnormal sperm significantly increased in the CP group compared to the control and ATRA groups. CP+ATRA administration significantly increased the sperm count and motility, but reduced the abnormal sperm count. CP administration significantly increased TOS and OSI compared to the control group and the other groups. Administering CP+ATRA significantly decreased TOS and the OSI in testicular tissue and reduced spermatogenesis, but increased the Johnsen score.ConclusionsThe destructive effects of CP treatment on testicular tissue and spermatogenesis were reduced by administering ATRA.