Testicular Lactate Dehydrogenase Research Articles

The Effect of Different Exercise Modalities on Sertoli-germ Cells Metabolic Interactions in High-fat Diet-induced Obesity Rat Models: Implication on Glucose and Lactate Transport, Igf1, and Igf1R-dependent Pathways.

The study aimed to uncover a unique aspect of obesity-related metabolic disorders in the testicles induced by a high-fat diet (HFD) and explored the potential mitigating effects of exercise modalities on male fertility. Thirty mature male Wistar rats were randomly assigned to control, HFD-sole, moderate-intensity exercise with HFD (HFD+MICT), high-intensity continuous exercise with HFD (HFD+HICT), and high-intensity interval exercise with HFD (HFD+HIIT) groups (n=6/group). Intracytoplasmic carbohydrate (ICC) storage, expression levels of GLUT-1, GLUT-3, MCT-4, Igf1, and Igf1R, and testicular lactate and lactate dehydrogenase (LDH) levels were assessed. ICC storage significantly decreased in HFD-sole rats, along with decreased mRNA and protein levels of GLUT-1, GLUT-3, MCT-4, Igf1, and Igf1R. The HFD-sole group exhibited a notable reduction in testicular lactate and LDH levels (p<0.05). Conversely, exercise, particularly HIIT, upregulated ICC storage, expression levels of GLUT-1, GLUT-3, MCT-4, Igf1, and Igf1R, and enhanced testicular lactate and LDH levels. These results confirm that exercise, especially HIIT, has the potential to mitigate the adverse effects of HFD-induced obesity on testicular metabolism and male fertility. The upregulation of metabolite transporters, LDH, lactate levels, Igf1, and Igf1R expression may contribute to maintaining metabolic interactions and improving the glucose/lactate conversion process. These findings underscore the potential benefits of exercise in preventing and managing obesity-related male fertility issues.

Fluted pumpkin seeds protect the spermatogenesis score index and testicular histology of caffeine treated rats.

The present study was designed to evaluate the protective effect of fluted pumpkin seeds (FPS) against caffeine (CAFF) induced testicular toxicity in rats. Thirty young healthy male Wistar rats (196 ± 12 g) were randomly organized into five sets of six animals per each group: control, caffeine (CAFF; 50 mg kg-1 bw) and FPS co-treatment groups (CAFF + 50 mg FPS, CAFF + 100 mg FPS and CAFF + 200 mg FPS kg-1 bw). CAFF and FPS were administered daily and twice per week respectively by oral gavage for 40 days. CAFF treatment decreased testicular lactate dehydrogenase enzyme activity level, which was attenuated on co-administration with FPS at 50 and 100 mg kg-1 bw. Furthermore, CAFF decreased seminiferous epithelia thickness and spermatogenesis score index and increased the number of tubules with abnormal histological features, which were attenuated on co-administration with FPS at 50 mg kg-1 bw much more than at the higher doses (p < 0.05). CAFF did not affect malondialdehyde and glutathione concentrations and glutathione peroxidase (GSH-Px) activity in the testes whereas FPS co-treatment at the higher doses elevated glutathione level and GSH-Px activity and did not affect spermatogenesis score index at the highest dose (200 mg kg-1 bw). Testicular malondialdehyde concentrations remained unaffected in all FPS co-treatment groups. Overall, FPS is able to minimize the CAFF-induced testicular injury at lower than at the higher tested doses.

P-001 L-arginine ameliorates maternal and pre-pubertal codeine exposure-induced dysregulation of testicular cytoprotective and spermatogenic genes and improves steroidogenesis in adult rat offspring

Abstract Study question Will maternal exposure to codeine cause transgenerational effect on testicular function and what role will pre-pubertal codeine-exposure and L-arginine treatment play? Summary answer L-arginine treatment blunted maternal and pre-pubertal codeine exposure-induced downregulation of testicular cytoprotective and spermatogenic genes and distortion of steroidogenesis. What is known already Codeine, a common drug of abuse, has been reported to impair male infertility by eliciting testicular and sperm damage via oxidative stress-sensitive pathway. On the other hand, L-arginine has been shown to improve testicular perfusion and testicular redox state, thus enhancing male reproductive function. However, no study has evaluated the effect of maternal codeine exposure and concurrent pre-pubertal codeine and L-arginine administration on male reproductive health viz a viz testicular steroidogenesis, spermatogenesis, and sperm quality. Study design, size, duration This is a prospective experimental study using animal model. Forty pre-pubertal female Wistar rats of comparable age and weight were used for the study. The study lasted two generations. Participants/materials, setting, methods Forty pre-pubertal female Wistar rats were randomized into vehicle-treated or codeine-treated. After 8 weeks of administration via gavage, animals were paired with stud male Wistar rats (1: 1). Administration continued throughout pregnancy and lactation. Male offsprings were weaned at post-natal day (PND) 21 and each cohort was randomized into vehicle treated, codeine-treated, L-arginine-treated, and codeine with L-arginine-treated. Offspring intervention commenced at PND 28 and lasted for 8 weeks. Main results and the role of chance Maternal codeine exposure caused increased testicular lactate dehydrogenase activity, concentrations of lactate and uric acid, and reduced testicular sorbitol dehydrogenase activity. In addition, maternal codeine exposure reduced testicular activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, and glutathione and Nrf2 concentrations, but increased testicular concentrations of malondialdehyde, 8OHdG, TNF-α, IL-1β, and NFkB, MPO and caspase 3 activities, and DNA fragmentation. Furthermore, codeine exposure reduced steroidogenic markers (3β-HSD, 17β-HSD, FSH, LH, and testosterone), indices of spermatogenesis, and sperm quality. This was associated with reduced expression of regulatory genes for spermatogenesis (mRNA of Ndrg4, Kit, Rhcg, Lrrc34, and Lgals1), and cytoprotection (mRNA SOD, mRNA GPx, and mRNA Nrf2), and increased mRNA TNF-α, mRNA NFkB, and mRNA caspase 3. The observed codeine-induced perturbations were worsened by pre-pubertal codeine exposure in offsprings damned by mothers with codeine exposure but blunted by L-arginine treatment. Limitations, reasons for caution This study is an animal model; therefore, findings should be extrapolated to human with care. Thus, human studies are recommended. Wider implications of the findings This study demonstrates for the first time the transgenerational effect of maternal codeine exposure, and the impact of concomitant pre-pubertal codeine use and L-arginine treatment. The present findings add to the available literature by providing further molecular mechanisms through which codeine impairs male reproductive function. Trial registration number not applicable

Acetate supplementation restores testicular function by modulating Nrf2/PPAR-γ in high fat diet-induced obesity in Wistar rats.

Several studies have established impaired testicular function in obese male population, including the young males with childhood obesity, contributing to increased male infertility, which is a universal trend in the last few decades. Short chain fatty acids (SCFAs) have been recently demonstrated to inhibit progression to metabolic comorbidities. The present study therefore hypothesized that SCFAs, acetate attenuates testicular dysfunction in high fat diet (HFD)-induced obese rat model, possibly by modulating Nrf2/PPAR-γ. Adult male Wistar rats weighing 160-190g were randomly allotted into three groups (n = 6/group): The groups received vehicle (distilled water), 40% HFD and sodium acetate (200mg/kg) plus 40% HFD respectively. The administration lasted for 12weeks. HFD caused obesity, which is characterized with increased body weight and visceral adiposity and insulin resistance/hyperinsulinemia. In addition, it increased testicular lipid deposition, malondialdehyde, pro-inflammatory mediators, lactate/pyruvate ratio, γ-Glutamyl transferase, and circulating leptin as well as decreased testicular glutathione, nitric oxide, Nrf2, PPAR-γ and circulating follicle stimulating hormone and testosterone without a significant change in testicular lactate dehydrogenase, blood glucose and luteinizing hormone when compared to the control group. Nevertheless, administration of acetate reversed the HFD-induced alterations. The present results demonstrates that HFD causes obesity-driven testicular dysfunction, associated with testicular lipid deposition, oxidative stress, and inflammation. The study in addition suggests the restoration of testicular function in obese animals by acetate, an effect that is accompanied by elevated Nrf2/PPAR-γ.

P–075 HAART exacerbates anti-Koch-induced reproductive toxicity via suppression of androgen and down-regulation of cGMP signaling

Abstract Study question Will highly active antiretroviral drugs (HAART) and antikochs impair reproductive function when used singly and concurrently? Summary answer HAART exacerbates antikoch-induced reproductive toxicity by stimulating testicular and penile oxido-inflammatory response. This was associated with suppression of androgen and down-regulation of cGMP signaling. What is known already Although the advent of HAART and antikochs has significantly improved the clinical status, life expectancy and quality of life of patients with HIV/tuberculosis, these drugs are with shortcomings. Studies have reported that HAART induces testicular toxicity and impairs sperm quality. Similarly, antikochs has been shown to trigger oxidative testicular and sperm damage. Available data have implicated HAART and antikoch in the pathogenesis of male infertility via oxidative stress-mediated mechanism. However, no study has reported the impact of the concurrent administration of both HAART and antikochs as seen in patients with TB/HIV co-infection on testicular function, sexual behaviour and fertility outcome. Study design, size, duration This is a prospective experimental study using animal model. Forty sexually mature inbred male Wistar rats of comparable age were used for the study. The study lasted 8 weeks. Participants/materials, setting, methods Animals were acclimatized for two weeks after which they were randomly allotted into four groups (n = 10). The control rats 0.5mL of distilled water as vehicle, anti-Koch-treated rats received a cocktail of anti-tuberculosis drugs (Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol), HAART-treated animals received a cock-tail of antiretroviral drugs (Efavirenz, Lamivudine, and Tenofovir), while the HAART+antikochs-treated rats received treatment as HAART-treated as well as antikoch-treated. The doses of drugs used were the Human Equivalent doses for rats. Main results and the role of chance HAART exaggerated antikoch-induced increase in testicular lactate dehydrogenase activity, concentrations of lactate and uric acid, and reduced testicular sorbitol dehydrogenase activity. Furthermore, HAART worsens antikoch-induced decline in the activities of testicular and penile superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase, as well as glutathione concentration, but increased malondialdehyde levels in testicular and penile tissues, as well as penile and testicular DNA fragmentation. Similarly, HAART aggravates antikoch-driven reduction in penile cGMP, circulatory and testicular testosterone, serum prolactin, LH and FSH, impaired sperm quality, sexual behaviour, and fertility outcome. Limitations, reasons for caution This is a prospective study using animal model; hence findings should be extrapolated to human with care. Human studies are thus recommended. Wider implications of the findings: This study demonstrates for the first time the impact of HAART and antikoch, when used singly or in combination, on sexual behaviour, sperm quality and penile and testicular integrity. The findings add to the available literature by providing the molecular mechanism through which HAART and/or antikoch possibly impair reproductive function. Trial registration number N/A

ROS and metabolomics-mediated autophagy in rat's testicular tissue alter after exercise training; Evidence for exercise intensity and outcomes

AimsOxidative damage and altered metabolic reactions are suspected to initiate the autophagy. The exercise training significantly impacts testicular antioxidant and metabolic potentials. However, the underlying mechanism(s) that the exercise-induced alterations can affect the autophagy markers remained unknown. This study explored the effect of exercise training on antioxidant and metabolic statuses of testicular tissue and uncovered the possible cross-link between these statuses and autophagy-inducers expression. Main methodsWistar rats were divided into sedentary control, low (LICT), moderate (MICT), and high (HICT) intensity continuous training groups. Following 8 weeks of training, the testicular total antioxidant capacity (TAC), total oxidant status (TOS), glutathione (GSH), and NADP+/NADPH as oxidative biomarkers along with intracytoplasmic carbohydrate and lipid droplet patterns, lactate dehydrogenase (LDH) activity, and lactate as metabolic elements were assessed. Finally, the autophagy-inducers expression and sperm count were examined. Key findingsWith no significant impact on the oxidative biomarkers and metabolic elements, the LICT and MICT groups exhibited statistically unremarkable (p < 0.05) impacts on spermatogenesis differentiation, spermiogenesis ratio, and sperm count while increased the autophagy-inducers expression. Reversely, the HICT group, simultaneous with suppressing the antioxidant biomarkers (TAC↓, GSH↓, TOS↑, NADP+/NADPH↑), significantly (p < 0.05) reduced the testicular LDH activity and lactate level, changed the intracytoplasmic carbohydrate and lipid droplet's pattern, and amplified the classical autophagy-inducers p62, Beclin-1, autophagy-related gene (ATG)-7, and light chain 3 (LC3)-II/I expression. SignificanceThe autophagy-inducers overexpression has occurred after HICT induction, most probably to eliminate the oxidative damage cargoes, while increased to maintain the metabolic homeostasis in the LICT and MICT groups.

In vivo and in silico evaluation of the ameliorative effect of hesperidin on finasteride-induced testicular oxidative stress in Wistar rats

Finasteride used for treating benign prostatic hyperplasia is associated with undesirable side effects via oxidative stress related mechanisms. This study employed in vivo and in silico methods to investigate the protective role of hesperidin against testicular toxicity induced by finasteride and the possible molecular mechanisms involved. Male Wistar rats were randomized into four groups of six animals each. Group I (control) were administered distilled water, group II received finasteride (3.1 mg/kg bw), group III received hesperidin (100 mg/kg bw), while group IV were co-administered finasteride and hesperidin. Administration was by gavage for 14 days. The binding propensities of finasteride and hesperidin for 5α-reductase were assessed using in silico docking approach. Finasteride administration caused significant reductions of sperm motility, volume, count, and live/dead ratio, with significant increase in numbers of abnormal sperms. Finasteride treatment also resulted in diminished activities of superoxide dismutase, catalase and glutathione-S-transferase, significant reduction in the concentration of reduced glutathione and ascorbic acid, and increased testicular malondialdehyde level relative to control. Moreover, significant increase in the activities of testicular lactate dehydrogenase and γ-glutamyl transferase was observed, with significant decrease in the activities of acid phosphatase and alkaline phosphatase relative to finasteride-treated rats. Furthermore, hesperidin exhibited favorable binding affinity for 5α –reductase (5AR) in silico compared to finasteride. Co-administration with hesperidin ameliorated finasteride-induced testicular damage by suppressing oxidative stress indices, enhancing antioxidant status, improving sperm parameters and alterations in the activities of marker enzymes, as well as possibly inhibiting the binding of finasteride to 5AR.

Role of bisphenol A on calcium influx and its potential toxicity on the testis of Danio rerio

This study investigated the acute in vitro effect of low-concentration bisphenol A (BPA) on calcium (45Ca2+) influx in zebrafish (Danio rerio) testis and examined whether intracellular Ca2+ was involved in the effects of BPA on testicular toxicity. In vitro studies on 45Ca2+ influx were performed in the testes after incubation with BPA for 30 min. Inhibitors were added 15 min before the addition of 45Ca2+ and BPA to testes to study the mechanism of action of BPA. The involvement of intracellular calcium from stores on lactate dehydrogenase (LDH) release and on triacylglycerol (TAG) content were carried out after in vitro incubation of testes with BPA for 1 h. Furthermore, gamma-glutamyl transpeptidase (GGT) and aspartate aminotransferase (AST) activities were analyzed in the liver at 1 h after in vitro BPA incubation of D. rerio. Our data show that the acute in vitro treatment of D. rerio testes with BPA at very low concentration activates plasma membrane ionic channels, such as voltage-dependent calcium channels and calcium-dependent chloride channels, and protein kinase C (PKC), which stimulates Ca2+ influx. In addition, BPA increased cytosolic Ca2+ by activating inositol triphosphate receptor (IP3R) and inhibiting sarco/endoplasmic reticulum calcium ATPase (SERCA) at the endoplasmic reticulum, contributing to intracellular Ca2+ overload. The protein kinases, PKC, MEK 1/2 and PI3K, are involved in the mechanism of action of BPA, which may indicate a crosstalk between the non-genomic initiation effects mediated by PLC/PKC/IP3R signaling and genomic responses of BPA mediated by the estrogen receptor (ESR). In vitro exposure to a higher concentration of BPA caused cell damage and plasma membrane injury with increased LDH release and TAG content; both effects were dependent on intracellular Ca2+ and mediated by IP3R. Furthermore, BPA potentially induced liver damage, as demonstrated by increased GGT activity. In conclusion, in vitro effect of BPA in a low concentration triggers cytosolic Ca2+ overload and activates downstream protein kinases pointing to a crosstalk between its non-genomic and genomic effects of BPA mediated by ESR. Moreover, in vitro exposure to a higher concentration of BPA caused intracellular Ca2+-dependent testicular cell damage and plasma membrane injury. This acute toxicity was reinforced by increased testicular LDH release and GGT activity in the liver.

Gum Arabic improves the reproductive capacity through upregulation of testicular glucose transporters (GLUTs) mRNA expression in Alloxan induced diabetic rat

Diabetes mellitus (DM) is a metabolic disorder and an endemic disease of the twenty-first century. DM-induced tissue damage is associated with testicular deregulation resulting in reduction of fertility. Gum Arabic (GA) is reported to improve reproductive function. In this study, 60 male Sprague-Dawley rats were divided into 3 groups (n = 20 of each): control group, diabetic group which were injected with Alloxan, and diabetic group which was given 10% GA in drinking water for 10 weeks. The effect of GA on sperm quality blood glucose, serum testosterone and 17β-estradiol levels were investigated. Lactate dehydrogenase (LDH) activities together with testis histopathological changes were measured. LDH and glucose transporters (GLUTs) genes mRNA were also evaluated. GA treatment significantly (P < 0.05) decreased food intake and blood glucose level compared to control and diabetic groups. GA Treatment significantly (P < 0.05) increased semen quality and serum testosterone levels compared to control and diabetic groups. Likewise, GA treatment significantly (P < 0.05) increased testicular LDH activity compared to the control group. Moreover, GA treatment significantly (P < 0.05) increased testicular GLUT1 and GLUT3 mRNA expression. Similarly, GA significantly (P < 0.05) increased testicular 3β-HSD and LDH mRNA expression compared to control. However, no effects were found in GLUT8 and GLUT9 mRNA expression. Diabetic rat's testis displayed obvious degeneration whereas; slight degeneration was seen in GA treated rats when compared to diabetic control group. These findings suggest that GA may improve reproductive function via enhancement of testicular GLUT1 and GLUT3 mRNA expression which may ameliorate diabetic fertility problems and complications.

Effect of Fe and Cd Co-Exposure on Testicular Steroid Metabolism, Morphometry, and Spermatogenesis in Mice.

The mechanism of testicular toxicity of simultaneous multiple exposures to metals is poorly understood. Previous studies reported that the toxic effect of cadmium (Cd) is modified by tissue concentration of iron (Fe). Using the mice (Mus musculus) model in the present study, we demonstrated that combined Cd (25mgkg-1 bw) and Fe (100mgkg-1 bw) treatment increased both Cd and Fe testicular concentrations much more than separate exposures to either of the metals. Intratesticular Cd and Fe concentrations were inversely correlated (r = - 0.731, p < 0.05) on administration of Fe but not on combined exposure to both metals when they were positively correlated (versus Cd; r = 0.793, versus Fe; r = 0.779, p < 0.05). Additionally, Cd + Fe treatment increased testicular lipid peroxidation and depleted intratestesticular testosterone, cholesterol and glutathione concentrations much more than their separate treatment. This was also associated with decreased activity of the germ cell marker, testicular lactate dehydrogenase, and increased testicular myeloperoxidase activity. These changes resulted in decreased seminiferous epithelial height, tubular diameter, germ cell (spermatogonia, spermatocytes, and spermatids) numbers, and severe tissue damage. In conclusion, Cd + Fe intake have synergistic toxic effects on testicular steroid formation and spermatogenesis due to the high testicular concentrations of both metals.

Co-administration of glutathione alleviates the toxic effects of 2,3,7,8 TCDF on the DNA integrity of sperm and in the testes of mice.

This study aimed to investigate the toxic impact prompted in the testes of adult mice exposed to 2,3,7,8-tetrachlorodibenzofuran (TCDF). Four groups of 12 mice each were used in the present study. Group 1 mice were kept as control and administered corn oil only. Group 2 animals were given glutathione (GSH) in a dose of 100mg/kg body weight by oral gavage twice a week. Group 3 was given TCDF orally twice per week, in a dose of 0.5μg/kg body weight for 8weeks. Group 4 was administered GSH orally in a dosage of 100mg/kg body weight plus TCDF twice a week for 8weeks. Animals were sacrificed after 2, 4, and 8weeks of exposure, serum samples were collected for estimation of testosterone hormone, the testes were dissected and one part was used for estimation of superoxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH), and 3β-hydroxysteroid dehydrogenase. Another portion of the testis was kept in formalin for histopathological examination. The results showed that the activities of SOD were decreased while the levels of lipid peroxidation MDA were increased in the testicular tissues of the exposed mice. The serum testosterone level and the steroidogenic enzyme 3β-hydroxysteroid dehydrogenase activity of testicular homogenate were essentially decreased in TCDF-treated mice. A significant increment in the testicular LDH activity in testicular tissues was recorded in mice exposed to TCDF. The percentage of DNA chromatin disintegration was significantly increased in TCDF-treated mice. Histopathological changes were recorded in TCDF-exposed group as degenerative changes of the seminiferous tubules with formation of spermatid giant cells at 2weeks in addition to exhaustion of germinal epithelium and detachment of the germ cells from the basal lamina at 4 and 8weeks. Co-administration of GSH could reestablish MDA and LDH levels besides reduction in percentage of sperm DNA damage and improvement of the testicular tissue architecture.

Fluazifop- p-butyl, an aryloxyphenoxypropionate herbicide, diminishes renal and hepatic functions and triggers testicular oxidative stress in orally exposed rats.

Fluazifop- p-butyl (FPB) is a selective aryloxyphenoxypropionate herbicide. Its phytotoxicity mechanism involves inhibition of lipid biosynthesis, free-radical generation, and oxidative stress in vulnerable plants. This study evaluates the impact of orally administered FPB on selected tissues in non-target animal model. Twenty-four male wistar rats (160-180g) were randomized into groups (I-IV). Group-I served as control, while animals in groups II, III, and IV received FPB at 18.75, 37.5, and 75 mg/kg body weight/day p.o., respectively, for 21 days. FPB caused significant ( p < 0.05) increase in plasma biomarkers of renal and hepatic function (urea, creatinine, bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase) when compared to control. Significant reductions in testicular ascorbic acid, glutathione, and activities of glutathione-S transferase, superoxide dismutase, and catalase were observed in FPB-treated animals when compared to control, in a dose-dependent manner. This was accompanied by increased testicular lipid peroxidation in the treated groups. Furthermore, a significant decrease in testicular acid phosphatase and γ-glutamyl transferase activities was also observed in the FPB-treated groups in a dose-dependent manner compared to control. However, testicular lactate dehydrogenase activity was significantly increased in the FPB-treated rats when compared to control. Additionally, histopathological studies revealed severe interstitial oedema and congestion of testicular blood vessels in the FPB-treated groups. Overall, data from this study suggest that FPB induced hepatotoxicity, nephrotoxicity, and oxidative stress-mediated alteration of testicular functions in rat.

Impact of electronic-cigarette refill liquid on rat testis

Electronic cigarettes (e-cigarettes) are becoming the fashionable alternative to decrease tobacco smoking, although their impact on health has not been fully assessed yet. The present study was designed to compare the impact of e-cigarette refill liquid (e-liquid) without nicotine to e-liquid with nicotine on rat testis. For this purpose, e-liquid with nicotine and e-liquid without nicotine (0.5 mg/kg of body weight) were administered to adult male Wistar rats via the intraperitoneally route during four weeks. Results showed that e-liquid with or without nicotine leads to diminished sperm density and viability, such as a decrease in testicular lactate dehydrogenase activity and testosterone level. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis identified a reduction in cytochrome P450 side-chain cleavage (P450 scc) and 17 beta-hydroxysteroid dehydrogenase (17βHSD) mRNA level, two key enzymes of steroidogenesis. Following e-liquid exposure, histopathological examination showed alterations in testis tissue marked by germ cells desquamation, disorganization of the tubular contents of testis and cell deposits in seminiferous tubules. Finally, analysis of oxidative stress status pointed an outbreak of antioxidant enzyme activities such as superoxide dismutase, catalase and gluthatione-S-transferase, as well as an important increase in sulfhydril group content. Taken together, these results indicate that e-liquid per se induces toxicity in Wistar rat testis, similar to e-liquid with nicotine, by disrupting oxidative balance and steroidogenesis.

Hepatotoxicity, Nephrotoxicity and Oxidative Stress in Rat Testis Following Exposure to Haloxyfop-p-methyl Ester, an Aryloxyphenoxypropionate Herbicide.

Haloxyfop-p-methyl ester (HPME) ((R)-2-{4-[3-chloro-5-(trifluoromethyl)-2-pyridyloxy]phenoxy}propionic acid), is a selective aryloxyphenoxypropionate (AOPP) herbicide. It exerts phytotoxicity through inhibition of lipid metabolism and induction of oxidative stress in susceptible plants. This study investigated the toxicological potentials of HPME in rats. Twenty-four male Wistar rats (170–210 g) were randomized into four groups (I–IV). Group I (control) received 1 mL of distilled water, while animals in Groups II, III and IV received 6.75, 13.5 and 27 mg/kg body weight HPME, respectively, for 21 days. There was a significant (p < 0.05) increase in renal and hepatic function biomarkers (urea, creatinine, total bilirubin, ALP, ALT, AST) in the plasma of treated animals compared to control. Levels of testicular antioxidants, ascorbic acid and glutathione, and activities of glutathione-S-transferase, superoxide dismutase and catalase were reduced significantly after 21 days of HPME administration in a dose-dependent manner. The testicular malondialdehyde level increased significantly in the HPME-treated rats relative to the control. A significant decrease in testicular lactate dehydrogenase, acid phosphatase and γ-glutamyl transferase was also observed in HPME-treated animals. Testicular histology revealed severe interstitial edema and sections of seminiferous tubules with necrotic and eroded germinal epithelium in the HPME-treated rats. Overall, data from this study suggest that HPME altered hepatic and renal function and induced oxidative stress and morphological changes in the testis of rats.

Dibutyl phthalate induces oxidative stress and impairs spermatogenesis in adult rats.

Phthalates are abundantly produced plasticizers, and dibutyl phthalate (DBP) is the most widely used derivative in various consumer products and medical devices. This study was conducted to further explore the potential testicular toxicity of DBP in adult rats and to elucidate the underlying mechanisms. Adult male albino rats were treated orally with DBP at doses of 0, 200, 400, or 600 mg/kg/day for 15 consecutive days. Testicular weight, sperm count, and motility were significantly decreased. Treatment with DBP decreased serum follicle-stimulating hormone and testosterone levels and testicular lactate dehydrogenase activity. DBP treatment also decreased serum total antioxidant capacity and the activities of the testicular antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione reductase. Further, DBP treatment provoked degeneration with absence of spermatogenesis and sperms and necrosis in some of seminiferous tubules. These results indicated that oxidative stress and subsequent decrease in testosterone secretion were the potential underlying mechanism of DBP-induced testicular toxicity.

The role of heat shock protein 70 induced by geranylgeranylacetone in carbon tetrachloride-exposed adult rat testes

Carbon tetrachloride (CCl4) induces testicular damage, through formation of free-radical metabolites. Molecular chaperone heat shock protein of 70kDa (HSP 70) protects cells from various stresses. This study was designed to investigate the potential role of induction of HSP70 using geranylgeranylacetone (GGA) on testicular damage caused by CCl4. Rats were divided into group I (control group), Group II (CCl4 group) received CCl4 s.c. for 4 weeks, group III received CCl4 s.c. for 4 weeks simultaneously with daily single oral dose of GGA (GGA – treated CCl4 group). Serum testosterone, testicular lactate dehydrogenase (LDH) and alkaline phosphatase (ALP), testicular malondialdehyde (MDA), total nitrite and total antioxidant capacity (T-AOC) were measured. Evaluation of histopathological changes and immunohistochemical HSP70 expression for testicular biopsies were performed. Group II showed lower values of gonado-somatic index, serum testosterone, testicular LDH, ALP, T-AOC and greater values of testicular MDA and total nitrite than in control. Testicular morphology showed widening of seminiferous lumen, less spermatogenesis, vacuolization of germinative epithelium. Group III had higher values of gonado-somatic index, serum testosterone, testicular LDH, ALP, T-AOC with less testicular MDA and total nitrite than in group II. They have less damage and restored the altered testicular morphology. Immunohistochemical HSP70 expression was increased in the testicular spermatogenic and sertoli cells in group II that was significantly accentuated in group III. These findings suggest that GGA-induced activation of HSP 70 significantly alleviate CCl4 inflicting testicular damage by HSP 70 mediated cytoprotection and antioxidant effects.

Selenium provides protection to the liver but not the reproductive organs in an atrazine-model of experimental toxicity

The present study evaluated the possible protective effects of selenium against atrazine-induced toxicity in the liver and reproductive system of rats. Atrazine administered to rats orally at a dose of 120 mg/kg caused an inhibition in the activity of glutathione-S-transferase and an increase in malondialdehyde formation in the liver, testis and epididymis. Superoxide dismutase decreased in the liver and testis but was increased in the epididymis. Furthermore, hepatic glutathione and lactate dehydrogenase activity increased while epididymal catalase, ascorbate content, hepatic aspartate aminotransferase and glutathione peroxidase activities in all the tissues decreased in the atrazine-treated animals. Hepatic, testicular and epididymal alanine aminotransferase activities were not affected by atrazine ( p>0.05). Decreased epididymal and testicular sperm number, sperm motility, daily sperm production and increased number of dead and abnormal sperm were observed in atrazine-treated rats. Treatment of rats orally with selenium at a dose of 0.25 mg/kg did not prevent atrazine-induced changes in sperm characteristics and had no protective effects against atrazine-induced biochemical alterations in the testis and epididymis except testicular lactate dehydrogenase. Catalase activity and ascorbate contents were unchanged in these groups of animals. However, selenium effectively protected against atrazine-induced changes in biochemical indices in the liver. In rats treated with selenium alone, glutathione peroxidase in all the tissues, hepatic glutathione and superoxide dismutase, testicular lactate dehydrogenase activity and ascorbate content increased, while hepatic catalase activities decreased ( p<0.05). Our data suggest that selenium effectively attenuated the toxic effects of atrazine-induced liver changes but not in the reproductive organs and sperms of rats. Selenium might therefore be useful in ameliorating oxidative stress in the liver.

Attractin gene deficiency contributes to testis vacuolization and sperm dysfunction in male mice

The effect of loss-of-function of Attractin (Atrn) on the male mouse reproduction system was examined in the study. The weights and pathological changes of testes and epididymes were compared between Atrn mutant (Atrn(mg-3J)) mice and wild-type mice (C3HeB/FeJ) at different months of age. The number and motility of sperms were measured in the mutant and control mice. Furthermore, the testicular lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in these animals were detected. The fertility potential of the sperms was observed in vivo and in vitro. The results showed that the testes of 3-month-old Atrn (mg-3J) mice experienced no significantly different pathological changes from the control mice at the same month of age but the SDH activity was substantially reduced. In the 5-month-old mutant mice, as compared with the control mice, mild vacuolation was found in the testes, the density and motility of sperms were decreased in the epididymes, the sperm fertility was impaired and the testicular enzyme activity was reduced. It is concluded that the age-related Atrn gene progressively loses its function and can cause testis vacuolation and impaired sperm function, which may be responsible for the impairment of male reproductive ability.

Effect of endosulfan during fetal gonadal differentiation on spermatogenesis in rats

Pregnant rats were exposed to endosulfan (1 or 2 mg/kg per day) from day 12 of gestation through parturition. Male neonates were fostered to untreated dams. At 100 days of age, the male offspring were sacrificed. Exposure to endosulfan during fetal gonadal differentiation altered the process of spermatogenesis by affecting testicular lactate dehydrogenase and sorbitol dehydrogenase. Reduction in spermatid count in testis and sperm count in cauda epididymis was observed. Testis, epididymis and seminal vesicle showed significant decrease in weights in both the treated groups while no effect on prostate weight was recorded. Hence it can be suggested that endosulfan interferes in the process of spermatogenesis. The overall toxicity was dose dependent.

Prevention of di(2-ethylhexyl)phthalate-induced testicular atrophy in rats by Co-administration of the vitamin B12 derivative adenosylcobalamin

The administration of 2g/kg of di(2-ethylhexyl)-phthalate (DEHP)-induced severe testicular atrophy coincident with the reduction of testicular specific lactate dehydrogenase (LDH-X) activity, zinc, magnesium, and potassium concentrations in rats. Co-administration of DEHP and adenosyl cobalamin (AdoCbl), one of the active vitamin B12s, prevented these testicular specific changes including fluctuations in testicular weight. On the other hand, co-administration of DEHP and methylcobalamin (MeCbl), the other active vitamin B12, did not prevent the testicular atrophy induced by DEHP under the present experimental conditions. In the liver, DEHP administration caused hypertrophy with changes in several metal concentrations and serum biochemical parameters. Co-administration of DEHP and AdoCbl or MeCbl did not prevent these hepatic changes, but aggravated hypolipidemia. The results demonstrated that the preventive effect of AdoCbl was a testicular specific action, and this effect may be stimulated solely by AdoCbl in vitamin B12 groups.