Polychlorinated biphenyls have inhibitory effect on testicular steroidogenesis by downregulation of P45017α and P450scc

2010 ◽  
Vol 26 (5) ◽  
pp. 287-296 ◽  
Author(s):  
Dae-Yong Han ◽  
Sang-Rim Kang ◽  
Oh-Sung Park ◽  
Jae-Hyeon Cho ◽  
Chung-Kil Won ◽  
...  

Polychlorinated biphenyls (PCBs) are environmental pollutants that are quite toxic to biological systems. This study examined the inhibitory effect of PCB126 and PCB114 on testicular steroidogenesis in male rats. Male Sprague Dawley rats received weekly intraperitoneal injections of PCB126 (0.2 mg/kg) or PCB114 (20 mg/kg) or vehicle (corn oil). Animals from each group were sacrificed at 2, 5 and 8 weeks after the injections. Blood and testis tissue samples were collected for the hormone assay, Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). The testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were assayed, and the expression levels of the mRNA and proteins associated with the testosterone biosynthesis pathway were measured to determine the effect of PCB126 and PCB114 on testicular steroidogenesis. The results showed that the testis weight was significantly higher in the PCB126-treated rats given eight shots. Moreover, the serum testosterone levels were significantly lower in the PCB126 and PCB114-treated groups than the control. The transcription and translation levels of P45017α and P450scc were significantly lower in the PCB126-treated groups than the control. These results suggest that PCB126 may affect testicular steroidogenesis by downregulating P45017α, P450 scc and have inhibitory effect on the testicular functions.

2021 ◽  
Vol 12 ◽  
Author(s):  
Bin Ji ◽  
Zina Wen ◽  
Chaobo Ni ◽  
Qiqi Zhu ◽  
Yiyan Wang ◽  
...  

Background: Diisoheptyl phthalate (DIHP) is a phthalate plasticizer, which is a branched phthalate. Here, we reported the effects of gestational exposure to DIHP on testis development in male rats.Methods: Pregnant Sprague-Dawley rats were orally fed with vehicle (corn oil, control) or DIHP (10, 100, 500, and 1,000 mg/kg) from gestational day (GD) 12–21. At GD21, serum testosterone levels, the number and distribution of fetal Leydig cells, and testicular mRNA and protein levels, the incidence of multinucleated gonocytes, and focal testicular hypoplasia in the neonatal testis were measured.Results: DIHP increased the fetal Leydig cell cluster size and decreased the fetal Leydig cell size with LOAEL of 10 mg/kg. DIHP did not affect the fetal Leydig cell number. DIHP significantly lowered serum testosterone levels, down-regulated the expression of steroidogenesis-related genes (Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3) and testis descent-related gene (Insl3) as well as protein levels of cholesterol side-chain cleavage enzyme (CYP11A1) and insulin-like 3 (INSL3). DIHP dose-dependently increased the percentage of multinucleated gonocytes with the low observed adverse-effect level (LOAEL) of 100 mg/kg. DIHP induced focal testicular hypoplasia.Conclusion: Gestational exposure to DIHP causes testis dysgenesis in rats.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Samar R. Saleh ◽  
Rana Attia ◽  
Doaa A. Ghareeb

This study was aimed at evaluating the efficacy of berberine-rich fraction (BF) as a protective and/or a therapeutic agent against inflammation and oxidative stress during male infertility. Sexually mature Sprague-Dawley male rats were divided into five groups treated with either corn oil, BF (100 mg/kg BW, orally, daily for 30 days), gossypol acetate (5 mg/kg BW, i.p.) eight times for 16 days, BF alone for 14 days then coadministered with gossypol acetate for the next 16 days (protected group), or gossypol acetate for 16 days then treated with BF for 30 days (treated group). All animals completed the experimental period (46 days) without obtaining any treatments in the gap period. Sperm parameters, oxidative index, and inflammatory markers were measured. Gossypol injection significantly decreased the semen quality and testosterone level that resulted from the elevation of testicular reactive oxygen and nitrogen species (TBARS and NO), TNF-α, TNF-α-converting enzyme, and interleukins (IL-1β, IL-6, and IL-18) by 230, 180, 12.5, 97.9, and 300%, respectively, while interleukin-12 and tissue inhibitors of metalloproteinases-3 were significantly decreased by 59 and 66%, respectively. BF (protected and treated groups) significantly improved the semen quality, oxidative stress, and inflammation associated with male infertility. It is suitable to use more advanced studies to validate these findings.


2019 ◽  
Vol 41 (1) ◽  
pp. 141-150 ◽  
Author(s):  
Hamid Karimi ◽  
Noor-Ahmad Latifi ◽  
Ali Zare Mehrjerdi ◽  
Babak Jafarnejad ◽  
Ali-Mohammad Karimi

Abstract Prevention of infections is a very important issue in treating the burn wounds. The nanosilver dressings have many promising advantages, but absorption of silver ions and its adverse effects to the body were always a question. The aim of this study was to compare Silver serum levels and acute toxic effects of nanosilver on histopathology of organs (lungs, liver, kidney, spleen, and brain) in two types of AgiCoat and Acticoat (nanosilver) dressings on second-degree deep burn in rat. This is an experimental study conducted in our animal laboratory. We divided 24 Sprague–Dawley male rats weighing 300 to 350 randomly into two groups. After anesthesia, a second deep-degree burn was made over dorsal skins of rats by standard method. For group A, Agicoat and, for group B, Acticoat dressings were used. The dressings were changed every 3 days with AgiCoat and Acticoat, respectively. After 14 days, we got blood samples and tissue samples taken from heart, liver, kidneys, spleen, lungs, and brain and a sample from dorsal skin of the rat for histopathological examinations. The results showed that the levels of serum silver in both groups were significantly higher than the standard level (1.22 part per million (PM); AgiCoat, P = .017; Acticoat, P = .000), but there was no significant difference between the groups (P = .551). Examination of the relationship between the level of serum silver and histopathological changes in liver showed that hepatotoxicity of AgiCoat was higher compared with Acticoat and the difference was significant (P = .002). There were no pathological changes in brain, kidneys, spleen, heart, and lungs. Wound healing was faster in Acticoat group. The nanosilver dressings can cause toxicity in liver but not in kidney, brain, spleen, heart, and lungs. Liver pathology and hepatotoxicity were more prominent in AgiCoat group. Wound healing was faster in Acticoat group.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1993 ◽  
Author(s):  
Guilherme Rizzoto ◽  
Deepa Sekhar ◽  
Jacob C. Thundathil ◽  
Prasanth K. Chelikani ◽  
John P. Kastelic

The objective was to determine effects of feed restriction and refeeding on reproductive development and energy balance in pre-pubertal male rats. Sprague Dawley rats (n = 32, 24 days old, ~65 g), were randomly allocated into four treatments (n = 8/treatment): (1) Control (CON, ad libitum feed; (2) Mild Restriction (MR, rats fed 75% of CON consumption); (3) Profound Restriction (PR, 50% of CON consumption); or (4) Refeeding (RF, 50% restriction for 14 days, and then ad libitum for 7 days). Feed restriction delayed reproductive development and decreased energy balance and tissue accretion, with degree of reproductive and metabolic dysfunctions related to restriction severity. In RF rats, refeeding largely restored testis weight, sperm production (per gram and total), plasma IGF-1, leptin and insulin concentrations and energy expenditure, although body composition did not completely recover. On Day 50, more CON and RF rats than PR rats were pubertal (5/6, 4/5 and 1/6, respectively; plasma testosterone >1 ng/mL) with the MR group (4/6) not different. Our hypothesis was supported: nutrient restriction of pre-pubertal rats delayed reproductive development, induced negative energy balance and decreased metabolic hormone concentrations (commensurate with restriction), whereas short-term refeeding after profound restriction largely restored reproductive end points and plasma hormone concentrations, but not body composition.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Shahira M. Ezzat ◽  
Marwa I. Ezzat ◽  
Mona M. Okba ◽  
Salah M. Hassan ◽  
Amgad I. Alkorashy ◽  
...  

Eurycoma longifolia Jack (Fam.: Simaroubaceae), known as Tongkat Ali (TA), has been known as a symbol of virility and sexual power for men. Metabolic profiling of the aqueous extract of E. longifolia (AEEL) using UPLC-MS/MS in both positive and negative modes allowed the identification of seventeen metabolites. The identified compounds were classified into four groups: quassinoids, alkaloids, triterpenes, and biphenylneolignans. AEEL is considered safe with oral LD50 cut-off >5000 mg/kg. Oral administration of 50, 100, 200, 400, or 800 mg/kg of AEEL for 10 consecutive days to Sprague-Dawley male rats caused significant reductions in mounting, intromission, and ejaculation latencies and increased penile erection index. AEEL increased total body weight and relative weights of seminal vesicles and prostate. Total and free serum testosterone and brain cortical and hippocampal dopamine content was significantly elevated in treated groups with no significant effects on serotonin or noradrenaline content.


1995 ◽  
Vol 7 (5) ◽  
pp. 1101 ◽  
Author(s):  
MP Hedger ◽  
S Khatab ◽  
G Gonzales ◽  
Kretser DM de

In this study, adult male rats were injected intraperitoneally with a single dose of serotonin (5-hydroxytryptamine, 5HT; 10 mg kg-1 bodyweight) for 2 h or 18 h, or daily with graded doses of 5HT (0.1-10 mg kg-1) for four days before being killed. Serum and testicular interstitial fluid (IF) concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and immunoreactive-inhibin were measured by radioimmunoassay, and one testis was removed for histological examination. At 2 h after a single injection, 5HT caused a significant inhibition of serum concentrations of LH and inhibin, recovered IF volume and intratesticular testosterone concentrations; testis weight and serum concentrations of testosterone and FSH were unaffected. At 18 h after injection, all parameters had returned to normal, with the exception of intratesticular testosterone concentration which remained lower than normal. The lowest 5HT dose (0.1 mg kg-1) had no effect on any parameter following four daily injections. At a dose of 1.0 mg kg-1 5HT, there was a four-fold increase in the concentration of serum LH, but testis weight, recovered IF volume, testosterone and inhibin concentrations and serum concentrations of FSH were not significantly affected. At the highest dose of 5HT (10 mg kg-1) after four daily injections, testis weight decreased, and IF volume increased nearly three-fold. Testis concentrations of inhibin and serum testosterone were reduced, whereas serum concentrations of both LH and FSH were elevated; intratesticular testosterone concentrations did not differ from controls. Only at the highest dose of 5HT was disruption to the seminiferous epithelium observed, with focal damage ranging in severity from increased degeneration of spermatogenic cell profiles, to complete loss of the germinal epithelium; however, many tubule profiles displayed completely normal spermatogenesis. The acute IF volume reduction and spermatogenic disruption in 5HT-treated rats were consistent with localized ischaemia due to constriction of the testicular arterial supply. The eventual increase in IF volume observed after 5HT treatment appeared to be secondary to the loss of germ cells. Although 5HT also inhibited pituitary LH release and Leydig cell steroidogenesis, these effects appeared to play only a minor role in the induction of spermatogenic damage.


2000 ◽  
Vol 25 (2) ◽  
pp. 207-219 ◽  
Author(s):  
AH Taylor ◽  
AE Fox-Robichaud ◽  
C Egan ◽  
J Dionne ◽  
DE Lawless ◽  
...  

Oestrogens protect against ischaemic heart disease in the post-menopausal female by increasing serum concentrations of apolipoprotein (apo) AI and the abundance of high-density lipoprotein particles. In men and experimental male animals, the administration of oestrogen has variable effects on apo AI expression. As the major mode of oestrogen action on target genes involves regulating promoter activity and hence transcription, oestrogen is expected to alter transcription of the apo AI gene. To test this hypothesis, the effect of 17beta-oestradiol (E(2)), on rat apo AI promoter activity in male hepatoma HuH-7 cells, was tested by co-transfecting a reporter template, pAI.474.CAT containing-474 to-7 of the rat apo AI promoter and an oestrogen receptor (ER) expression vector, pCMV-ER. Transfected cells exposed to E(2) showed a dose-dependent decrease in chloramphenicol acetyltransferase (CAT)-activity, with a maximum 91+/-1.5% reduction at 1 microM E(2). Deletional analysis of the promoter localized the inhibitory effect of ER and E(2) to site B (-170 to-144) with an adjacent 5' contiguous motif, site S (-186 to-171) acting as an amplifier. HuH-7 cell nuclear extracts showed binding activities with both sites S and B, but recombinant human ER did not. Furthermore, nuclear extracts from E(2)-treated HuH-7 cells showed weaker binding activity to site B, but not to site S. In summary, the inhibitory effect of ER and E(2) on rat apo AI gene activity is mediated by a promoter element, site B. This inhibitory effect arises from a mechanism that does not involve direct ER binding to the B-element. The conclusion that E(2) inhibits apo AI transcription was confirmed in vivo. Treatment of male adult Sprague-Dawley rats with up to 200 microg E(2) for 7 days decreased apo AI protein and hepatic mRNA by 72+/-21% and 68+/-1.4% respectively. Results of 'run-on' transcription of the apo AI gene in isolated hepatic nuclei showed a 55% decrease in hormone-treated male rats. These findings suggest that E(2) exerts primarily an inhibitory effect within male hepatic nuclei.


1976 ◽  
Vol 83 (1) ◽  
pp. 190-200 ◽  
Author(s):  
H. L. Verjans ◽  
K. B. Eik-Nes

ABSTRACT Testes of adult, male rats were exposed to a total dose of 1500 R of X-irradiation. Testicular weight decreased from day 8 after X-ray treatment. This decrease was, however, preceded by an increment of the testis weight on day 4 following treatment. X-ray treatment of testes was associated with significant increases in serum FSH. Testicular irradiation had, however, no effect on ventral prostate and seminal vesicles weights. Serum testosterone increased only on day 1, 2 and 4 after irradiation, while serum LH levels tended to increase from day 8 post-irradiation. These changes were not significant, however, when compared with non-irradiated controls. At 7, 13 and 20 days following 1500 R of bilateral, testicular X-irradiation, the hypothalamic-pituitary unit was still capable of responding to exogenous gonadotrophin releasing factor. Serum FSH may in male rats be regulated at least partly by circulating steroids of testicular origin and partly by an unknown factor of non-interstitial cell nature.


2020 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mohammad Kheradmandpour ◽  
Seyed Abolfazl Aminifar ◽  
Mahin Dianat

: Ocimum basilicum (OB) contains more than 30 plant species that are found in different regions, especially in Africa. OB contains various substances, especially Chavikol, Methyl Ether or Strangol, Linalool, and Agenol, which have antioxidant, antihypertensive, antidiabetic, and anti-lipid properties. On the other hand, along with lifestyle changes, the prevalence of cardiovascular diseases, such as arrhythmias, which cause high mortality, is increasing. Moreover, the modern drugs used for arrhythmia can also induce another type of abnormal heart rhythm. Regarding the effectiveness and fewer side effects of herbal medicine, we decided to study the preventive effects of hydro-alcoholic extract of OB on CaCl2-induced arrhythmias in rats. Male rats (Sprague-Dawley) were divided into the control group (2 weeks, normal saline, gavage) and three groups receiving different concentrations of hydro-alcoholic extract of OB (100, 200, and 400 mg/kg, gavage for 2 weeks). The arrhythmia model was established using CaCl2 (IV, 140 mg/kg). The number of ventricular fibrillation (VF), ventricular premature (PVC), and ventricular tachycardia (VT) were studied. Also, the oxidative stress parameters, such as malondialdehyde (MDA) and superoxide dismutase (SOD), were measured in heart tissue samples. Statistical analysis was done using Fisher's exact test and ANOVA, and also, P < 0.05 was considered as a significant level. The obtained results showed that administration of OB caused a decrease in MDA and an increase in SOD levels, which were associated with improved electrocardiogram parameters and reduced cardiac arrhythmias, which suggests the therapeutic potential of the plant in cardiovascular disorders.


2019 ◽  
Vol 35 (11-12) ◽  
pp. 679-687 ◽  
Author(s):  
Bahar Ulus Karaca ◽  
Yağmur Emre Arican ◽  
Tugce Boran ◽  
Sevgi Binay ◽  
Alper Okyar ◽  
...  

Acetamiprid, a selective agonist of type-2 nicotinic acetylcholine receptors, is one of the most widely used neonicotinoids. The hepato- and nephrotoxic potential of acetamiprid has not been clarified although it is known to be toxic to other several organ systems, including the nervous, respiratory and immune systems. The present study aimed to investigate acetamiprid liver and kidney toxicity in male rats after a 90-day subchronic exposure to 12.5, 25 and 35 mg/kg. The biochemical and oxidative damage parameters were determined in the plasma and tissue samples as well as histopathological evaluation in the liver and kidney tissues. Acetamiprid caused oxidative damage and affected the liver, denoted by injury markers including the levels of cholesterol, and alanine aminotransferase and aspartate aminotransferase enzymes. There was also a decrease in plasma urea, uric acid and creatinine levels, all of which might result from liver injury. Additionally, acetamiprid was more toxic to the liver than the kidney according to the histopathological examinations. In conclusion, acetamiprid exhibited hepatotoxic potential at all treatment doses on male Sprague Dawley rats.


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