scholarly journals Morphological and morphometric changes and epithelial apoptosis are induced in the rat epididymis by long-term letrozole treatment

2021 ◽  
Vol 65 (3) ◽  
Author(s):  
Anna Pilutin ◽  
Kamila Misiakiewicz-Has ◽  
Sylwia Rzeszotek ◽  
Barbara Wiszniewska
Keyword(s):  
Chronic Treatment ◽  
Treated Group ◽  
Male Rats ◽  
Apoptotic Cells ◽  
Aromatase Inhibition ◽  
Adult Rats ◽  
Morphological Evaluation ◽  
Letrozole Treatment ◽  
Rat Epididymis

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.

Gender-related long-term effects in adult rats by perinatal dietary ratio of n-6/n-3 fatty acids

2005 ◽  
Vol 288 (3) ◽  
pp. R575-R579 ◽  
Author(s):  
Marina Korotkova ◽  
Britt G. Gabrielsson ◽  
Agneta Holmäng ◽  
Britt-Marie Larsson ◽  
Lars Å. Hanson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Linseed Oil ◽  
Maternal Diet ◽  
Perinatal Period ◽  
Late Gestation ◽  
Male Rats ◽  
Long Term Effects ◽  
Adult Rats ◽  
Serum Leptin

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.

Changes in Sleep Architecture under Sustained Pain in Adult Male Rats Subjected to Neonatal Short-Lasting Local Inflammatory Insult

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
Keyword(s):  
Paradoxical Sleep ◽  
Sleep Architecture ◽  
Male Rats ◽  
Intraplantar Injection ◽  
Quiet Sleep ◽  
Adult Rats ◽  
Physiological Relevance ◽  
Highly Correlated ◽  
Stimulation Of

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.

scholarly journals Dentate Gyrus Proliferative Responses After Traumatic Brain Injury and Binge Alcohol in Adult Rats

2020 ◽  
Vol 15 ◽  
pp. 263310552096890
Author(s):  
Son T Ton ◽  
Natalie S Adamczyk ◽  
Jack P Gerling ◽  
Ian C Vaagenes ◽  
Joanna Y Wu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dentate Gyrus ◽  
Proliferative Response ◽  
Male Rats ◽  
Public Health Issue ◽  
Adult Rats ◽  
Double Labeling ◽  
Post Traumatic

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.

scholarly journals Repeated exposure to chlorpyrifos is associated with a dose-dependent chronic neurobehavioral deficit in adult rats

2021 ◽  
Author(s):  
Ana CR Ribeiro ◽  
Elisa H Hawkins ◽  
Fay M Jahr ◽  
Joseph L McClay ◽  
Laxmikant S Deshpande
Keyword(s):  
Molecular Mechanisms ◽  
Low Dose ◽  
Forced Swim Test ◽  
Preference Test ◽  
Complete Recovery ◽  
Male Rats ◽  
High Dose ◽  
Adult Rats ◽  
Dose Dependent

Organophosphate (OP) chemicals include commonly used pesticides and also chemical warfare agents, and mechanistically they are potent inhibitors of the cholinesterase (ChE) enzyme. While a chronic low-dose OP exposure does not produce acute cholinergic crises, epidemiological studies report long-term neuropsychiatric issues including depression and cognitive impairments in OP-exposed individuals. Chlorpyrifos (CPF) is one of the most widely used pesticides worldwide. Multiple laboratory studies have reported on either the long-term behavioral effect of a single, high-dose CPF or studied sub-chronic behavioral effects particularly the motor and cognitive effects of repeated low-dose CPF exposure. However, studies on chronic mood and depression-related morbidities following repeated sub-threshold CPF doses that would mimic occupationally-relevant OP exposures are lacking. Here, adult male rats were injected with CPF (1, 3, 5, or 10 mg/kg/d, s.c.) for 21-days. Dependent on the CPF dose, ChE activity was inhibited approximately 60-80% in the blood and about 20-50% in the hippocampus at 2-days after the end of CPF exposures. Following an 11-week washout period, CPF-treated rats exhibited a dose-dependent increase in signs of anhedonia (sucrose preference test), anxiety (open-field and elevated plus-maze), and despair (forced swim test) despite a complete recovery of ChE activity at this stage. We speculate that both cholinergic and non-cholinergic mechanisms could play a role in the development of chronic OP-related depressive outcomes. The proposed CPF exposure paradigm could provide an ideal model to further study molecular mechanisms underlying cause and effect relationships between environmental OP exposures and the development of chronic behavioral deficits.

scholarly journals EXPERIMENTAL EVALUATION OF LONG-TERM ADVERSE SIDE EFFECTS OF CYTOSTATIC DRUGS ON FEMALE REPRODUCTIVE FUNCTION AND PHARMACOLOGICAL WAYS TO REDUCE THEM

2021 ◽  
Vol 20 (1) ◽  
pp. 87-96
Author(s):  
T. G. Borovskaya ◽  
V. E. Goldberg ◽  
M. E. Poluektova ◽  
A. V. Vychuzhanina ◽  
Yu. A. Shchemerovа ◽  
...  
Keyword(s):  
Ovarian Reserve ◽  
Structural Damage ◽  
Reproductive Potential ◽  
Reproductive Function ◽  
Female Rats ◽  
Male Rats ◽  
Fetal Mortality ◽  
Cytostatic Drugs ◽  
Adult Rats

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. 

scholarly journals Peripubertal aromatase inhibition in male rats has adverse long-term effects on bone strength and growth and induces prostatic hyperplasia

2010 ◽  
Vol 207 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Anurag Bajpai ◽  
Peter J Simm ◽  
Stephen J McPherson ◽  
Vincenzo C Russo ◽  
Walid J Azar ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Bone Strength ◽  
Aromatase Inhibitors ◽  
Final Height ◽  
Prostatic Hyperplasia ◽  
Male Rats ◽  
Long Term Effects ◽  
Aromatase Inhibition ◽  
Long Term Adverse Effects

Aromatase inhibitors have been increasingly used in boys with growth retardation to prolong the duration of growth and increase final height. Multiple important roles of oestrogen in males point to potential adverse effects of this strategy. Although the deleterious effects of aromatase deficiency in early childhood and adulthood are well documented, there is limited information about the potential long-term adverse effects of peripubertal aromatase inhibition. To address this issue, we evaluated short-term and long-term effects of peripubertal aromatase inhibition in an animal model. Peripubertal male Wistar rats were treated with aromatase inhibitor letrozole or placebo and followed until adulthood. Letrozole treatment caused sustained reduction in bone strength and alteration in skeletal geometry, lowering of IGF1 levels, inhibition of growth resulting in significantly lower weight and length of treated animals and development of focal prostatic hyperplasia. Our observation of adverse long-term effects after peripubertal male rats were exposed to aromatase inhibitors highlights the need for further characterisation of long-term adverse effects of aromatase inhibitors in peripubertal boys before further widespread use is accepted. Furthermore, this suggests the need to develop more selective oestrogen inhibition strategies in order to inhibit oestrogen action on the growth plate, while beneficial effects in other tissues are preserved.

scholarly journals Preclinical Evaluation of Safety and Biodistribution of Red Cell Microparticles: A Novel Hemostatic Agent

2019 ◽  
Vol 24 (5) ◽  
pp. 474-483
Author(s):  
Ashish K. Rehni ◽  
Vibha Shukla ◽  
Hever Navarro Quero ◽  
Carlos Bidot ◽  
Conner R. Haase ◽  
...  
Keyword(s):  
Negative Impact ◽  
Blood Gases ◽  
Treated Group ◽  
Physiological Parameters ◽  
Male Rats ◽  
Hemostatic Agent ◽  
Red Cell ◽  
Mortality And Morbidity ◽  
Spleen And Lymph Nodes

Background:Uncontrollable bleeding is a major cause of mortality and morbidity worldwide. Effective hemostatic agents are urgently needed. Red cell microparticles (RMPs) are a highly promising hemostatic agent. This study evaluated the safety profile of RMPs preliminary to clinical trial.Methods and Results:RMPs were prepared from type O+ human red blood cell by high-pressure extrusion. Male rats were treated with RMPs either a 1 × bolus, or 4 × or 20 × administered over 60 minutes. The vehicle-treated group was used as a control. Effects on physiological parameters were evaluated; namely, blood pressure, body and head temperature, hematocrit, and blood gases. We did not observe any adverse effects of RMPs on these physiological parameters. In addition, brain, heart, and lungs of rats treated with 4 × dose (bolus followed by infusion over 60 minutes) or vehicle were examined histologically for signs of thrombosis or other indications of toxicity. No thrombosis or indications of toxicity in brain, heart, or lungs were observed. Studies revealed that RMPs were distributed mainly in liver, spleen, and lymph nodes, and were potentially excreted through the kidneys.Conclusions:Our study indicates that RMP administration appears not to have any negative impact on the parameters studied and did not produce thrombosis in heart, brain, and lungs. However, more detailed long-term studies confirming the safety of RMP as a hemostatic agent are warranted.

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 ◽  
...  
Keyword(s):  
Gnrh Antagonist ◽  
Survival Rates ◽  
Adult Survivors ◽  
Male Rats ◽  
Adult Rats ◽  
Histological Changes ◽  
Before And After ◽  
Testicular Injury ◽  
To Receive

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.

scholarly journals Laryngeal Neuromuscular Response to Short- and Long-Term Vocalization Training in Young Male Rats

2019 ◽  
Vol 62 (2) ◽  
pp. 247-256 ◽  
Author(s):  
Charles Lenell ◽  
Bethany Newkirk ◽  
Aaron M. Johnson
Keyword(s):  
Muscle Fiber ◽  
Neuromuscular Junctions ◽  
Young Male ◽  
Male Rats ◽  
Adult Rats ◽  
Vocal Training ◽  
Neuromuscular Response ◽  
Fiber Size ◽  
Short And Long Term

Purpose Although vocal training is often purported to restore and rebalance laryngeal muscle function, little is known about the direct effects of vocal training on the laryngeal muscles themselves. Consequently, parameters of vocal exercise dose, such as training duration and intensity, have not been well defined. The goal of this study was to use a behavioral animal model to determine the effects of short- and long-term ultrasonic vocalization (USV) training on USV acoustics, thyroarytenoid (TA) muscle neuromuscular junctions (NMJs), and TA muscle fiber size in adult rats. Method Twenty-four young adult male Long-Evans rats were divided into 3 groups (untrained control, 4-week training, and 8-week training). Baseline and posttraining USVs were recorded and acoustically analyzed for fundamental frequency, frequency bandwidth, amplitude, and duration. Presynaptic and postsynaptic NMJ morphological features and muscle fiber size were measured in the TA. Results USV training had no effect on USV acoustics. Eight weeks of USV training, however, resulted in a lower NMJ motor endplate dispersion ratio, consistent with previous findings. USV training did not affect fiber size within the TA muscle. Conclusions This study demonstrated that 8 weeks of USV training can induce peripheral neural adaptations in the NMJ of the TA muscle in young rats. The observed adaptations suggest that vocal training is consistent with endurance-type exercise, but the adaptations occur on a longer time scale than similar adaptations in the limb muscles.

scholarly journals STRESS DURING PUBERTY FACILITATES PRECANCEROUS PROSTATE LESIONS IN ADULT RATS

2017 ◽  
Vol 39 (4) ◽  
pp. 269-275 ◽  
Author(s):  
D Herrera-Covarrubias ◽  
G A Coria-Avila ◽  
M E Hernandez ◽  
N Ismail
Keyword(s):  
Mononuclear Cells ◽  
Precancerous Lesions ◽  
Male Rats ◽  
Ventral Prostate ◽  
Immune Challenge ◽  
Long Term Effects ◽  
Adult Rats ◽  
Abnormal Nucleus ◽  
Hematoxylin And Eosin Stain

Puberty can be a critical period for the long-term development of diseases, especially for stress-related disorders that depend on neuroendocrine and immune responses. Some organs like the prostate are prone to diseases that result from neuroendocrine or immune challenges, such as cancer. Aim: In the present study, we assessed the long-term effects of an acute pubertal stressor (immune-challenge) on the development of precancerous lesions in adult rats, and compared them with testosterone-induced prostatic lesions. Materials and Methods: Pubertal male rats received a single injection of lipopolysaccharide (LPS) or saline during puberty (5 weeks old). At adulthood (8 weeks old) males were subcutaneously implanted with either an empty capsule or filled with testosterone propionate (100 mg/kg). This resulted in a total of five groups: 1) intact untreated, 2) saline-treated and implanted with a blank capsule, 3) saline-treated and implanted with a testosterone capsule, 4) LPS-treated and implanted with a blank capsule, 5) LPS-treated and implanted with a testosterone capsule. Four weeks later, the rats were sacrified and their prostates processed for histology (hematoxylin and eosin stain) and blood serum processed for hormone analysis (testosterone and corticosterone). Results: Males treated with LPS (stressed during puberty via immune challenge) expressed epithelium dysplasia (specially in the ventral prostate), anisocytosis, presence of mononuclear cells, anisokariosis, non-basal polarity, abnormal nucleus-cytoplasm ratio, proplastic myoepithelium, and granular content in the lumen. These histological alterations were similar, but less severe than those observed in males implanted with testosterone during adulthood. Conclusion: These results indicate that pubertal exposure to an immune challenge (stress) facilitates the long-term development of prostatic lesions in adult male rats.

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