scholarly journals GnRH Antagonist Improves Pubertal Cyclophosphamide-Induced Long-Term Testicular Injury in Adult Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Rongrong Xie ◽  
Linqi Chen ◽  
Haiying Wu ◽  
Ting Chen ◽  
Fengyun Wang ◽  
...  

Background. Gonadal injury following chemotherapy is of increasing importance with the continuous improvement of survival rates. The protection of gonadotropin hormone antagonist (GnRHant) in long-term adult survivors of adolescent cancers and some autoimmune diseases has not yet been evaluated. Methods. The present study was aimed at longitudinally exploring whether the GnRHant could alleviate testicular damage induced by cyclophosphamide (CPA) in a rat model. Pubertal male rats were assigned to receive CPA with and without GnRHant. CPA was administrated at a single dose (100 mg/kg). GnRHant was started one hour prior to CPA injection and continued for four weeks (0.1 mg/kg, 3 times a week). Body and testes weights, testicular hormones, histological changes, and expression of androgen receptor (AR) in the testis were analyzed when rats matured into adulthood and completed a round of spermatogenesis. Results. Our results showed that body weight, histological injury, and AR expression in the testis were improved in the GnRHant + CPA group. However, testes weight and testicular hormones (anti-Müllerian hormone, inhibin B, and testosterone) did not markedly change. Conclusion. Our results indicate that the GnRHant administration before and after CPA in pubertal rats can protect long-term testicular injury induced by CPA via increased AR expression in the testes.

1989 ◽  
Vol 123 (1) ◽  
pp. 83-91 ◽  
Author(s):  
K.-L. Kolho ◽  
I. Huhtaniemi

ABSTRACT The acute and long-term effects of pituitary-testis suppression with a gonadotrophin-releasing hormone (GnRH) agonist, d-Ser(But)6des-Gly10-GnRH N-ethylamide (buserelin; 0·02, 0·1, 1·0 or 10 mg/kg body weight per day s.c.) or antagonist, N-Ac-d-Nal(2)1,d-p-Cl-Phe2,d-Trp3,d-hArg(Et2)6,d-Ala10-GnRH (RS 68439; 2 mg/kg body weight per day s.c.) were studied in male rats treated on days 1–15 of life. The animals were killed on day 16 (acute effects) or as adults (130–160 days; long-term effects). Acutely, the lowest dose of the agonist decreased pituitary FSH content and testicular LH receptors, but with increasing doses pituitary and serum LH concentrations, intratesticular testosterone content and weights of testes were also suppressed (P< 0·05–0·01). No decrease was found in serum FSH or in weights of accessory sex organs even with the highest dose of the agonist, the latter finding indicating continuing secretion of androgens. The GnRH antagonist treatment suppressed pituitary LH and FSH contents and serum LH (P< 0·05–0·01) but, as with the agonist, serum FSH remained unaltered. Testicular testosterone and testis weights were decreased (P <0·01) but testicular LH receptors remained unchanged. Moreover, the seminal vesicle and ventral prostate weights were reduced, in contrast to the effects of the agonists. Pituitary LH and FSH contents had recovered in all adult rats treated neonatally with agonist and there was no effect on serum LH and testosterone concentrations or on fertility. In contrast, in adult rats treated neonatally with antagonist, weights of testis and accessory sex organs remained decreased (P <0·01–0·05) but hormone secretion from the pituitary and testis had returned to normal except that serum FSH was increased by 80% (P <0·01). Interestingly, 90% of the antagonist-treated animals were infertile. It is concluded that treatment with a GnRH agonist during the neonatal period does not have a chronic effect on pituitary-gonadal function. In contrast, GnRH antagonist treatment neonatally permanently inhibits the development of the testis and accessory sex organs and results in infertility. Interestingly, despite the decline of pituitary FSH neonatally, neither of the GnRH analogues was able to suppress serum FSH values and this differs from the concomitant changes in LH and from the effects of similar treatments in adult rats. Journal of Endocrinology (1989) 123, 83–91


2005 ◽  
Vol 288 (3) ◽  
pp. R575-R579 ◽  
Author(s):  
Marina Korotkova ◽  
Britt G. Gabrielsson ◽  
Agneta Holmäng ◽  
Britt-Marie Larsson ◽  
Lars Å. Hanson ◽  
...  

Epidemiological studies in humans have shown that perinatal nutrition affects health later in life. We have previously shown that the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) in the maternal diet affects serum leptin levels and growth of the suckling pups. The aim of the present study was to investigate the long-term effects of various ratios of the dietary n-6 and n-3 PUFA during the perinatal period on serum leptin, insulin, and triacylglycerol, as well as body growth in the adult offspring. During late gestation and throughout lactation, rats were fed an isocaloric diet containing 7 wt% fat, either as linseed oil (n-3 diet), soybean oil (n-6/n-3 diet), or sunflower oil (n-6 diet). At 3 wk of age, the n-6/n-3 PUFA ratios in the serum phospholipids of the offspring were 2.5, 8.3, and 17.5, respectively. After weaning, all pups were given a standard chow. At the 28th postnatal wk, mean body weight and fasting insulin levels were significantly increased in the rats fed the n-6/n-3 diet perinatally compared with the other groups. The systolic blood pressure and serum triacylglycerol levels were only increased in adult male rats of the same group. These data suggest that the balance between n-6 and n-3 PUFA during perinatal development affects several metabolic parameters in adulthood, especially in the male animals.


2017 ◽  
Vol 39 (5) ◽  
pp. 386-398
Author(s):  
Cheryl C.H. Yang ◽  
Shiang-Suo Huang ◽  
Chun-Ting Lai ◽  
Terry B.J. Kuo ◽  
Ya-Chun Chu

Neonatal, short-lasting, local, nociceptive insult by carrageenan can cause long-term alterations in somatosensory and neurohumoral systems. We previously revealed hyporesponsiveness of the autonomic nervous system (ANS) after painful stimulation of adult rats in a neonatal carrageenan-induced pain model. Sleep disturbance has been highly correlated with pain and ANS activity. In the present study, adult rats that had received an intraplantar injection of carrageenan on postnatal day 1 were investigated to determine if there were alterations in their sleep architecture upon the stimulation of pain. Polysomnographic and heart rate variability recordings were carried out, with a wireless transmission of data, for 24 h under baseline conditions and after an intraplantar injection of complete Freund's adjuvant to induce sustained nociception. Increased active awake (AW) and decreased quiet sleep (QS) and paradoxical sleep (PS) times were noted in the control animals. In the carrageenan-treated rats, the AW time increased but with decreased alertness, as revealed by decreases in beta and increases in theta power. The QS time did not decrease. The PS time decreased during the first 12 h, then increased during the following 12 h, suggesting an early rebound of formerly deprived PS time. Sympathetic activation under sustained pain was not apparent in any stage of sleep in carrageenan-treated rats and was even suppressed in AW time. An impaired sympathetic reaction to pain may have contributed to the atypical changes in sleep architecture in these rats. In conclusion, pain in early life has a long-term effect on the cardiovascular-autonomic-electroencephalographic responses to pain later in life. The physiological relevance of these results remains undetermined.


Author(s):  
І. А. Samborska ◽  
O. Ye. Маievskyi ◽  
Z. M. Nebesna

Hyperhomocysteinemia is a well-known risk factor for atherosclerosis, coronary heart disease, stroke, and venous thrombosis. However, in recent decades, the range of diseases associated with elevated homocysteine levels has expanded significantly. The influence of this amino acid on the occurrence and development of pathologies of the respiratory system, in particular, chronic obstructive pulmonary disease, bronchial asthma, lung and pleural cancer, is currently being actively studied. The aim of the study is to find the features of histological changes in the lungs of adult rats under conditions of hyperhomocysteinemia. The experimental study was performed on 22 white nonlinear adult (6-8 months) male rats. During the experiment, the animals were divided into two groups – control and experimental. Simulation of the state of persistent hyperhomocysteinemia was achieved by administering to rats the experimental group of thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrally for 60 days. Histological specimens were studied using an SEO CCAN light microscope and photo-documented using a Vision CCD Camera with an image output system from histological specimens. Histological examinations of the lungs of adult animals under conditions of hyperhomocysteinemia revealed adaptive-compensatory and destructive changes in the components of the organ. Discirculatory disorders, remodeling of the bronchial wall with the formation of inflammatory infiltrates in them were revealed. Significant areas of dys- and atelectasis and emphysematically altered areas of the parenchyma were found in the respiratory tract of the lungs. In the alveolar septa, peribronchially and paravasally, histo- and leukocyte infiltration, formation of inflammatory conglomerates were determined. Remodeling of vascular walls, especially the microcirculatory tract leads to disruption of blood supply to the body and hypoperfusion of lung tissue.


2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Remigius Ibe Onoja ◽  
Chinwe Uzoma Chukwudi ◽  
Emmanuel Uchechukwu Ugwueze ◽  
Davinson Chuka Anyogu ◽  
Wilson Obidah ◽  
...  

Abstract Background Cadmium (Cd) is a known metallohormone which mimics the action of steroid hormones with adverse effect on testicular function. It is highly toxic and a prevalent environmental contaminant with no conventional antidote. This study investigates the possible ameliorative effects of Thymus vulgaris extract on testicular toxicity induced by Cd in male rats. Results The testicular and epididymal weights, serum concentration of follicle stimulating hormone, luteinizing hormone, and testosterone were significantly (p ≤ 0.05) lower in the cadmium-treated group compared to the control. Necrosis of germ cells of the seminiferous tubules was observed in the testicular tissues of the cadmium-treated group. Administration of extract showed mild but non-significant (p ≥ 0.05) protective effect on the cadmium-induced decrease in sex hormones and sperm count as well as oxidative stress and histological changes. Conclusion Thymus vulgaris leaf extract had weak ameliorative effect on cadmium-induced testicular injury in rats but with promising antioxidant activity.


Author(s):  
V. I. Zhilkin ◽  
O. M. Tsiroulnikova

Durable protection from hepatitis B virus (HBV) and other vaccine-preventable diseases assumes great importance due to improved long-term patient and graft survival rates in pediatric liver transplantation (PLT). Vaccine immunogenicity data in transplanted children is limited. The review presents aspects of current approach for childhood HBV immunization schedule prior to transplant, duration of time since transplant for receive booster dose, target median HBsAb levels before and after PLT. The latest data about types of vaccine against HBV and vaccine effectiveness in PLT centers in the world are also presented.


2020 ◽  
Vol 15 ◽  
pp. 263310552096890
Author(s):  
Son T Ton ◽  
Natalie S Adamczyk ◽  
Jack P Gerling ◽  
Ian C Vaagenes ◽  
Joanna Y Wu ◽  
...  

Background: Traumatic brain injury is a significant public health issue that results in serious disability in survivors. Traumatic brain injury patients are often intoxicated with alcohol when admitted to the hospital; however, it is not clear how acute intoxication affects recovery from a traumatic brain injury. Our group has previously shown that binge alcohol prior to traumatic brain injury resulted in long-term impairment in a fine sensorimotor task that was correlated with a decreased proliferative and neuroblast response from the subventricular zone. However, whether binge alcohol prior to traumatic brain injury affects the proliferative response in the hippocampal dentate gyrus is not yet known. Methods: Male rats underwent binge alcohol (3 g/kg/day) by gastric gavage for 3 days prior to traumatic brain injury. Cell proliferation was labeled by BrdU injections following traumatic brain injury. Stereological quantification and immunofluorescence confocal analysis of BrdU+ cells in the hippocampal dorsal dentate gyrus was performed at 24 hours, 1 week and 6 weeks post traumatic brain injury. Results: We found that either traumatic brain injury alone or binge alcohol alone significantly increased dentate gyrus proliferation at 24 hours and 1 week. However, a combined binge alcohol and traumatic brain injury regimen resulted in decreased dentate gyrus proliferation at 24 hours post-traumatic brain injury. At the 6 week time point, binge alcohol overall reduced the number of BrdU+ cells. Furthermore, more BrdU+ cells were found in the dentate hilar region of alcohol traumatic brain injury compared to vehicle traumatic brain injury groups. The location and double-labeling of these mismigrated BrdU+ cells was consistent with hilar ectopic granule cells. Conclusion: The results from this study showed that pre-traumatic brain injury binge alcohol impacts the injury-induced proliferative response in the dentate gyrus in the short-term and may affect the distribution of newly generated cells in the dentate gyrus in the long-term.


2021 ◽  
Vol 65 (3) ◽  
Author(s):  
Anna Pilutin ◽  
Kamila Misiakiewicz-Has ◽  
Sylwia Rzeszotek ◽  
Barbara Wiszniewska

The epididymis is an organ that plays a key role in sperm maturation. The aim of this study was to examine the association between the chronic treatment of mature male rats with letrozole and morphological evaluation and morphometric values of epididymis as well as changes in the number of apoptotic cells in epididymal epithelium. Adult rats were treated with letrozole for 6 months and the epididymis weight, morphology, morphometric values and the number of apoptotic cells in  the epithelium were examined. Long-term aromatase inhibition resulted in presence of intraepithelial clear vacuoles, hyperplasia of clear cells and a hyperplastic alteration in the epithelium known as a cribriform change. Moreover, changes in diameters of the epididymal duct and the epididymal lumen and changes in the epididymal epithelium height were observed. The number of apoptotic epithelial cells was increased in letrozole-treated group. It can be indicated that chronic treatment with letrozole can affect morphology, morphometric values and apoptosis in the epididymis of adult male rats. Observed changes are similar to that observed in the aging processes and may also be important for patients treated with aromatase inhibitors.


2021 ◽  
Vol 20 (1) ◽  
pp. 87-96
Author(s):  
T. G. Borovskaya ◽  
V. E. Goldberg ◽  
M. E. Poluektova ◽  
A. V. Vychuzhanina ◽  
Yu. A. Shchemerovа ◽  
...  

The purpose of the study was a comparative experimental assessment of long-term toxic effects of cytostatic drugs (epirubicin, etoposide, platidiam, carboplatin, paclitaxel) on the female reproductive function and search for pharmacological ways to reduce them.Material and Methods. Experiments were carried out on 200 outbred male rats, Wistar stock, 2.5 months old. Antitumor drugs were administered once, intravenously, in maximum tolerated dose. The reproductive status in rats was assessed 90 and 180 days after injection of cytostatic drugs. Correction of ovariotoxicity of cytostatic drugs was carried out using a recombinant human granulocyte colony stimulating factor (rhG-CS F, Neupomax, FARMSTA NDA RT-UfaVITA OJSC , Russia) and liquid extract of Scutellaria Baikalsky («GNTsLS », Kharkov). The mating and fertility ability of female rats as well as pre- and post-implantation fetal mortality were determined. Ovarian reserve was evaluated using morphological analysis of the ovaries using quantitative assessments of structural damage. Concentration of anti-Muller hormone in the blood of adult rats-females receiving etoposide and rhG-CS F were evaluated by enzyme immunoassay (IFA, ELISA , Cloud clone, Corp. Wuhan). Statistical processing of obtained experimental data was performed using Mann-Whitney U-test and Fisher angular transformation.Results. The mating and fertility ability of animals was found to be persisted. However, signs of early depletion of the ovarian reserve and a decrease in reproductive potential were observed. The risk of early menopause was increased to a greater extent after using epirubicin, etoposide and paclitaxel, and to a lesser extent after platidiam and carboplatin. The reproductive potential of animals was reduced due to increased fetal death. Platinum-containing drugs were found to be the most toxic. G-CS F was the effective drug for protecting the ovarian reserve from cytostatic effects. The use of Scutellaria baicalensis extract increased the reproductive potential of animals by reducing the rate of embryonic death. 


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