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.     

Psychostimulant-Induced Testicular Toxicity in Mice: Evidence of Cocaine and Caffeine Effects on the Local Dopaminergic System

Several organ systems can be affected by psychostimulant toxicity. However, there is not sufficient evidence about the impact of psychostimulant intake on testicular physiology and catecholaminergic systems. The aim of the present study was to further explore potential toxic consequences of chronic exposure to cocaine, caffeine, and their combination on testicular physiology. Mice were injected with a 13-day chronic binge regimen of caffeine (3x5mg/kg), cocaine (3×10mg/kg), or combined administration. Mice treated with cocaine alone or combined with caffeine showed reduced volume of the seminiferous tubule associated to a reduction in the number of spermatogonia. Cocaine-only and combined treatments induced increased lipid peroxidation evaluated by TBARS assay and decreased glutathione peroxidase mRNA expression. Importantly, caffeine-cocaine combination potentiated the cocaine-induced germ cell loss, and induced pro-apoptotic BAX protein expression and diminished adenosine receptor A1 mRNA levels. We analyzed markers of dopaminergic function in the testis and detected the presence of tyrosine hydroxylase (TH) in the cytoplasm of androgen-producing Leydig cells, but also in meiotic germs cells within seminiferous tubules. Moreover, using transgenic BAC-Drd1a-tdTomato and D2R-eGFP mice, we report for the first time the presence of dopamine receptors (DRs) D1 and D2 in testicular mouse Leydig cells. Interestingly, the presence of DRD1 was also detected in the spermatogonia nearest the basal lamina of the seminiferous tubules, which did not show TH staining. We observed that psychostimulants induced downregulation of DRs mRNA expression and upregulation of TH protein expression in the testis. These findings suggest a potential role of the local dopaminergic system in psychostimulant-induced testicular pathology.     

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.     

Effects of Quercetin against Doxorubicin-Induced Testicular Toxicity in Male Rats

Biology Bulletin - This study investigated the protective effects of quercetin (QUE) in doxorubicin (DOX)-induced testicular toxicity in rats. In the present study, testicular histomorphometry, the...     

Effects of Indomethacin on Acute, Subacute, and Latent Infections in Mice and Rats

The comparative effect of indomethacin and hydrocortisone on the resistance of mice or rats to various acute, subacute, and latent bacterial infections was investigated. Large daily doses of indomethacin and hydrocortisone administered to mice challenged with bacterial pathogens, including Klebsiella pneumoniae AD, Salmonella schottmuelleri 3010, Staphylococcus aureus (Smith), Streptococcus pyogenes C203, Salmonella pullorum #2, Proteus vulgaris 1810, and Pseudomonas aeruginosa 2616, revealed that in essentially all of these acute infections, the mortality of the infected mice treated with indomethacin was essentially identical to that found in the infected controls. In contrast, hydrocortisone often lowered the resistance of mice to these acute infections. In a more chronic bacterial infection due to Corynebacterium kutscheri, hydrocortisone produced striking deleterious effects on resistance, whereas indomethacin administration in doses approaching the maximal tolerated level caused no observable adverse effects on host resistance. Indomethacin fed continuously to rats for 80 days, at maximal tolerated levels, caused no observable adverse effects on the host-parasite relationship of rats which were shown to harbor various latent infections. Hydrocortisone administration, however, lowered the resistance of rats as evidenced by increased mortality related directly to extensive bacterial infection. Insofar as infection is concerned, indomethacin behaved like other nonsteroid anti-inflammatory agents such as aspirin and phenylbutazone.     

Ameliorative Effects of Selenium on Cadmium-Induced Injury in the Chicken Ovary: Mechanisms of Oxidative Stress and Endoplasmic Reticulum Stress in Cadmium-Induced Apoptosis

Despite the well-established toxicity of cadmium (Cd) to animals and the ameliorative effects of selenium (Se), some specific mechanisms in the chicken ovary are not yet clarified. To explore the mechanism by which the toxicity effect of Cd is induced and explore the effect of supranutritional Se on Cd toxicity in female bird reproduction, forty-eight 50-day-old Isa Brown female chickens were divided randomly into four groups. Group I (control group) was fed the basic diet containing 0.2 mg/kg Se. Group II (Se-treated group) was fed the basic diet supplemented with sodium selenite (Na₂SeO₃), and the total Se content was 2 mg/kg. Group III (Se + Cd-treated group) was fed the basic diet supplemented with Na₂SeO₃; the total Se content was 2 mg/kg, and it was supplemented with 150 mg/kg cadmium chloride (CdCl₂). Group IV (Cd-treated group) was with the basic diet supplemented with 150 mg/kg CdCl₂. The Cd, estradiol (E2), and progestogen (P4) contents changed after subchronic Cd exposure in chicken ovarian tissue; subsequently, oxidative stress occurred and activated the endoplasmic reticulum (ER) pathway to induce apoptosis. Further, Se decreased the accumulation of Cd in ovarian tissue, increased the E2 and P4 contents, alleviated oxidative stress, and reduced apoptosis via the ER stress pathway. The present results demonstrated that Cd could induce apoptosis via the ER stress pathway in chicken ovarian tissue and that Se had a significant antagonistic effect. These results are potentially valuable for finding a strategy to prevent Cd poisoning.     

Tetrahydrocurcumin Protects against Cadmium-Induced Hypertension,Raised Arterial Stiffness and Vascular Remodeling in Mice

Background

Cadmium (Cd) is a nonessential heavy metal, causing oxidative damage to various tissues and associated with hypertension. Tetrahydrocurcumin (THU), a major metabolite of curcumin, has been demonstrated to be an antioxidant, anti-diabetic, anti-hypertensive and anti-inflammatory agent. In this study, we investigated the protective effect of THU against Cd-induced hypertension, raised arterial stiffness and vascular remodeling in mice.

Methods

Male ICR mice received CdCl₂ (100 mg/l) via drinking water for 8 weeks. THU was administered intragastrically at dose of 50 or 100 mg/kg/day concurrently with Cd treatment.

Results

Administration of CdCl₂ significantly increased arterial blood pressure, blunted vascular responses to vasoactive agents, increased aortic stiffness, and induced hypertrophic aortic wall remodeling by increasing number of smooth muscle cells and collagen deposition, decreasing elastin, and increasing matrix metalloproteinase (MMP)-2 and MMP-9 levels in the aortic medial wall. Supplementation with THU significantly decreased blood pressure, improved vascular responsiveness, and reversed the structural and mechanical alterations of the aortas, including collagen and elastin deposition. The reduction on the adverse response of Cd treatment was associated with upregulated eNOS and downregulated iNOS protein expressions, increased nitrate/nitrite level, alleviated oxidative stress and enhanced antioxidant glutathione. Moreover, THU also reduced the accumulation of Cd in the blood and tissues.

Conclusions

Our results suggest that THU ameliorates cadmium-induced hypertension, vascular dysfunction, and arterial stiffness in mice through enhancing NO bioavailability, attenuating oxidative stress, improving vascular remodeling and decreasing Cd accumulation in other tissues. THU has a beneficial effect in moderating the vascular alterations associated with Cd exposure.     

Zinc Deficiency Promotes Testicular Cell Apoptosis in Mice

Biological Trace Element Research - Zinc (Zn) plays an important role in spermatogenesis, and carbon tetrachloride (CCl4) induces testicular oxidative damage and cell death. The objective of the...     

Cadmium-Induced Oxidative Stress in the Rat Testes: Protective Effects of Betaine

The aim of the present study was to evaluate the antioxidant effects of betaine against oxidative stress and pathological changes mediated by cadmium in the testes of rats. The adult male Wistar rats were allocated into three experimental groups as follows: the cadmium group received cadmium chloride at the dosage of 2 mg/kg intraperitoneally thereafter, the rats treated by physiological saline for 10 consecutive days. The betaine plus cadmium group received betaine at the dosage of 1.5 % w/w of the total diet orally for 10 consecutive days and cadmium chloride injected at the 2nd day of the betaine treatment. The control rats were injected physiological saline. Both testes of rats were removed for antioxidant assay and pathological changes evaluation on days 5 and 10 after cadmium toxicity. TBARS concentration (as a lipid peroxidation marker) was significantly higher in the cadmium group by day 10 compared to control and betaine plus cadmium groups, and it was significantly higher in cadmium group by day 5 in comparison with the controls. Catalase (CAT) and glutathione peroxidase activities decreased significantly by day 10 in cadmium group when compared to the controls. In contrast, CAT and superoxide dismutase activities increased significantly by day 10 in betaine plus cadmium group when compared to the cadmium group. In addition, the antioxidant effects of betaine could prevent testicular pathological changes in betaine plus cadmium group. The present data allow us to exploit the advantages of this nutrient agent in future studies.     

双酚A对雄性小鼠生殖毒性的影响

目的观察环境雌激素双酚A（BPA）对雄性小鼠生殖功能的损害作用。方法采用小鼠腹腔注射双酚A,染毒成年小鼠5d,饲养30d。观察小鼠精子畸形率、测定血清中一氧化氮（NO）的含量、一氧化氮合酶（NOS）的活性。以雌二醇（E2）作为阳性对照物。结果BPA染毒组小鼠的精子畸形率较对照组高,睾丸和附睾的脏器系数均低于对照组,血清NO含量、NOS活性均高于对照组。结论一定剂量的BPA对小鼠的精子有致畸作用,并可使血清NO含量、NOS活性增高。     

红剑鱼、孔雀鱼、食蚊鱼亚慢性毒性试验

目的研究一种快速评价有毒化学品对红剑鱼、孔雀鱼、食蚊鱼慢性毒性的试验方法。方法选择<3d龄的红剑鱼、孔雀鱼、食蚊鱼幼鱼开始暴露,试验药物为国际标准参比毒物Cr6 、Cu2 、Zn2 和Cd2 ,试验温度为25±1℃,每天更换试验液1次,试验持续5d。依据试验鱼的每尾干重和现存量作为观察指标,测定了铬、锌、铜、镉对红剑鱼、孔雀鱼和食蚊鱼的无可观察效应浓度(NOEC)和最低可观察效应浓度(LOEC)。结果铬、锌、铜、镉对红剑鱼和食蚊鱼的NOEC分别是2500、100、10、10μg/L,LOEC分别是5000、200、20、20μg/L。铬、锌、铜、镉对孔雀鱼的NOEC分别是2500、100、10、20μg/L,LOEC分别是5000、200、20、40μg/L;这与7天亚慢性试验结果相接近。结论红剑鱼、孔雀鱼、食蚊鱼,亚慢性毒性试验可从7d缩短为5d。     

Protective Effects of Selenium on Cadmium-Induced Brain Damage in Chickens

Selenium (Se) is an important dietary micronutrient with antioxidative roles. Cadmium (Cd), a ubiquitous environmental pollutant, is known to cause brain lesion in rats and humans. However, little is reported about the deleterious effects of subchronic Cd exposure on the brain of poultry and the protective roles on the brain by Se against Cd. The aim of this study was to investigate the protective effects of Se on Cd-induced brain damage in chickens. One hundred twenty 100-day-old chickens were randomly assigned to four groups and were fed a basal diet, or Se (as 10 mg Na₂SeO₃/kg dry weight of feed), Cd (as 150 mg CdCl₂/kg dry weight of feed), or Cd?+?Se in their basic diets for 60 days. Then, concentrations of Cd and Se, production of nitric oxide (NO), messenger RNA (mRNA) level and activity of inducible NO synthase (iNOS), level of oxidative stress, and histological and ultrastructural changes of the cerebrum and cerebellum were examined. The results showed that Cd exposure significantly increased Cd accumulation, NO production, iNOS activities, iNOS mRNA level, and MDA content in the cerebrum and cerebellum. Cd treatment obviously decreased Se content and antioxidase activities and caused histopathological changes in the cerebrum and cerebellum. Se supplementation during dietary Cd obviously reduced Cd accumulation, NO production, mRNA level and activity of iNOS, oxidative stress, and histopathological damage in the cerebrum and cerebellum of chickens. It indicated that Se ameliorates Cd-induced brain damage in chickens by regulating iNOS-NO system changes, and oxidative stress induced by Cd and Se can serve as a potential therapeutic for Cd-induced brain lesion of chickens.     

Effects of Alleles at the W Locus on Testicular Luteinizing Hormone Receptors in Adult Mice

Abstract

The autoregulation of testicular LH receptors was studied in W^x/W^v mice with germ cell aplasia and in normal (±/±) mice. To assess the effects of each individual allele, W^x/± and W^v/± mice were also examined. Basal testicular LH receptor concentration was higher in W^x/W^v mice than in all other genotypes, and higher in W^x/± than in ±/± mice. Twenty-four h after injection of 0.3 IU hCG/g bw, LH receptor concentration was decreased in ±/± and W^v/± mice, but not in W^x/W^v or W^x/± animals. Administration of hCG caused a significant increase in plasma testosterone levels in all genotypes. However, injection of the highest dose of hCG used (0.9 IU/g bw) caused a significantly greater elevation in plasma testosterone in W^x/W^v than in ±/± mice. Plasma gonadotropin levels were significantly higher in W^x/W^v mice than in all other genotypes. The present results indicate that the W^x allele is responsible for the changes in testicular function observed in W^x/W^v mice, and suggest that this allele may be involved in the genetic regulation of testicular LH receptors in the mouse.     

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.     

Protective Effects of Lactobacillus plantarum CCFM8610 against Acute Cadmium Toxicity in Mice

This study evaluated the protective effects of Lactobacillus plantarum CCFM8610, a selected probiotic with good cadmium binding capacity, against acute cadmium toxicity in mice. Ninety mice were divided into prevention and therapy groups. In the prevention groups, CCFM8610 was administered at 10⁹ CFU once daily for 7 days, followed by a single oral dose of cadmium chloride at 1.8 mg cadmium for each mouse. In the therapy groups, the same dose of CCFM8610 was administered for 2 days after an identical single dose of cadmium exposure. Mice that received neither cadmium nor culture or that received cadmium alone served as negative and positive controls, respectively. The effects of both living and dead CCFM8610 on cadmium ion concentrations in feces, liver, and kidney were determined. Moreover, the alterations in reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and histopathology in the liver and kidney were investigated. The results showed that compared to the mice that received cadmium only, CCFM8610 treatment can effectively decrease intestinal cadmium absorption, reduce tissue cadmium accumulation, alleviate renal and hepatic oxidative stress, and ameliorate hepatic histopathological changes. Living CCFM8610 administered after cadmium exposure offered the most significant protection. Our results suggested that CCFM8610 is more effective against acute cadmium toxicity than a simple antioxidant treatment due to its special physiological functions and that it can be considered a new dietary therapeutic strategy against acute cadmium toxicity.