scholarly journals Gender Difference Response of Male and Female Immunodeficiency Rats Treated with Tissue-specific Biomolecules

2019 ◽  
Vol 20 (3) ◽  
pp. 245-253 ◽  
Author(s):  
Liliya V. Fedulova ◽  
Alexandr A. Basov ◽  
Ekaterina R. Vasilevskaya ◽  
Stepan S. Dzhimak

Background:The modern immunology is targeted to the detailed study of various immunopathological conditions at the molecular and cellular level, development of new methods for the prevention, diagnostics and treatment of contagious and non-contagious diseases of humans and animals.Methods:In the present work we took the rats with model of cyclophosphamide-induced immunodeficiency and studied the features of gender impact of the complex extract of immunocompetent organs (thymus, spleen and mesenteric lymph nodes) Sus scrofa and its separate fraction with molecular weight less than 30 kDa administered to male and female rats.Results:The impact of gender differences and tissue-specific biomolecules (30 kDa fraction) on hematological parameters (leukocytes, erythrocytes, platelets), functional activity of immune system (IL-2, IL-4, IL-6, complement system, IgG, IgM), biochemical parameters of hepatocytes functioning (activity of ALP and LDG), carbohydrate metabolism (glucose) and lipid metabolism (triglycerides).Conclusion:Decrease of ALP activity is caused by inhibition of bile formation in a liver after introduction of cytostatic agent, and in contrast to complex extract, the administration of fraction 30 kDa allows improving bile production in male rats.

2020 ◽  
Vol 70 (2) ◽  
pp. 239-247
Author(s):  
Kremena Saracheva ◽  
Petar Hrischev ◽  
Liliya Vasileva ◽  
Mariyan Topolov ◽  
Julia Nikolova ◽  
...  

AbstractThe introduction of the second generation triptans in clinical and experimental practice was a major progress in the pharmacotherapy of migraine. Frovatriptan is a second generation triptan with strong 5-HT1B/1D serotonergic agonism and low 5-HT1A/7 receptor affinity, while almotriptan possesses not only the typical 5-HT1B/1D receptor agonist activity, but shows an affinity to the 5-HT1F receptor. The aim of our study was to assess the impact of frovatriptan and almotriptan on hemodynamics in male and female rats. We used a non-invasive “tail-cuff” method to measure the arterial blood pressure. Female and male Wistar rats were treated separately with high and low dosages of frovatriptan and almotriptan. Male and female rats showed reduction in all hemodynamic parameters, but only male rats showed an increase in the heart rate. In general, we could say that both almotriptan and frovatriptan potentiate cardiovascular safety.


1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.


Author(s):  
Olga Wronikowska ◽  
Maria Zykubek ◽  
Łukasz Kurach ◽  
Agnieszka Michalak ◽  
Anna Boguszewska-Czubara ◽  
...  

Abstract Rationale Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. Objectives The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats. Methods The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively. Results Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus. Conclusions Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A11-A11
Author(s):  
Joel Raymond ◽  
Nicholas Everett ◽  
Anand Gururajan ◽  
Michael Bowen

Abstract Introduction Oxytocin is a versatile hypothalamic neuropeptide involved in diverse neurobehavioural processes. Since oxytocin can elicit anxiolytic and serenic effects, one could hypothesise that oxytocin should prime the brain for sleep and promote hypnogenesis. However, based on the social salience hypothesis—that oxytocin promotes prosocial behaviour and directs attention toward social stimuli—one could also posit that oxytocin should promote wakefulness. At present, little research has comprehensively characterised the effect of oxytocin on sleep-wake behaviour and no explanation to reconcile these two seemingly competing hypotheses has been proposed. Methods This study investigated the effects of oxytocin on sleep-wake outcomes using radiotelemetry-based polysomnography in adult male and female Wistar rats. Oxytocin was administered via the intraperitoneal (IP; 0.1, 0.3 and 1 mg/kg) and intranasal (IN; 0.06, 1, 3 mg/kg) routes. Caffeine (IP and IN; 10 mg/kg) was also administered as a wake-promoting positive control. Additionally, pre-treatment with the oxytocin receptor (OTR) antagonist L-368,899 (IP; 5 mg/kg) and vasopressin 1a receptor (V1aR) antagonist SR49059 (IP; 1 mg/kg) followed by oxytocin (IP; 1 mg/kg) was conducted to determine which receptor(s) mediated sleep-wake effects of oxytocin. Results In both male and female rats, IP oxytocin produced dose-dependent effects on sleep-wake behaviour. Specifically, oxytocin initially promoted quiescent wakefulness (a restful but conscious state) at the cost of reducing both active wakefulness and sleep. Throughout the 1.5-hour period post-administration, oxytocin delayed REM sleep onset and reduced the proportion of both NREM and REM sleep. Conversely, IN oxytocin did not significantly alter any sleep-wake parameters at any dose tested. Caffeine demonstrated wake-promoting effects under both the IP and IN routes of administration. The involvement of OTR and V1aR binding in oxytocin-induced effects on sleep-wake outcomes will be discussed. Conclusion These findings appear to reconcile the two competing hypotheses: in rats, IP oxytocin appears to promote a state of quiescent wakefulness—one of calm and rest, but also of conscious responsivity to environmental stimuli. IN oxytocin demonstrated little to no effect on sleep-wake behaviour, which is a crucial finding given the escalating use of IN oxytocin as a therapeutic for conditions with comorbid disordered sleep. Support (if any) None.


2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Maryam Malek ◽  
Mehdi Nematbakhsh

Background. Angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor (ACE2/Ang-1-7/MasR) appears to counteract most of the deleterious actions of angiotensin-converting enzyme/angiotensin II/angiotensin II receptor 1 (ACE/Ang II/AT1R) in renal ischemia/reperfusion (I/R) injury but ACE2 activity and its levels are sexually dimorphic in the kidney. This study was designed to evaluate the effects of activation endogenous ACE2 using the diminazene aceturate (DIZE) in renal I/R injury in male and female rats.Methods. 36 Wistar rats were divided into two groups of male and female and each group distinct to three subgroups (n=6). I/R group was subjected to 45 min of bilateral ischemia and 24 h of reperfusion, while treatment group received DIZE (15 mg/kg/day) for three days before the induction of I/R. The other group was assigned as the sham-operated group.Results. DIZE treatment in male rats caused a significant decrease in blood urea nitrogen (BUN), creatinine, liver functional indices, serum malondialdehyde (MDA), and increase kidney nitrite levels (P<0.05), and in female rats a significant increase in creatinine and decrease serum nitrite levels compared to the I/R group (P<0.05).Conclusions. DIZE may protect the male kidney from renal I/RI through antioxidant activity and elevation of circulating nitrite level.


2012 ◽  
Vol 7 (6) ◽  
pp. 980-986 ◽  
Author(s):  
Milan Marounek ◽  
Zdeněk Volek ◽  
Eva Skřivanová ◽  
Marian Czauderna

AbstractMale and female rats were fed diets supplemented with cholesterol and palm fat at 10 and 50 g/kg, respectively; serum, hepatic tissue and faeces were analysed. Cholesterol supplementation significantly increased serum and hepatic cholesterol both in male and female rats. Male and female rats fed the cholesterol-containing diet differed significantly in serum cholesterol concentration (2.48 µmol/mL vs 2.92 µmol/mL), concentration of serum triacylglycerols, but not in hepatic cholesterol concentration. The serum and hepatic cholesterol concentrations correlated non-significantly in male rats (r=0.491; P=0.063) and significantly in female rats (r=0.818; P<0.001). Cholesterol supplementation non-significantly decreased relative expression of the hepatic LDL receptor gene and significantly increased relative expression of the hepatic cholesterol 7α-hydroxylase gene in rats of both genders. The faeces of control rats contained similar amounts of cholesterol and bile acids. Cholesterol supplementation increased cholesterol concentration 10 times in the faeces of male rats and 12 times in faeces of female rats. The corresponding increases of bile acid concentration were much lower (83% in male rats and 108% in female rats). It can be concluded that the effects of cholesterol supplementation were more pronounced in female than in male rats.


2002 ◽  
Vol 22 (2) ◽  
pp. 183-195 ◽  
Author(s):  
Aigang Lu ◽  
Rui-qiong Ran ◽  
Joseph Clark ◽  
Melinda Reilly ◽  
Alex Nee ◽  
...  

Estradiol reduces brain injury from many diseases, including stroke and trauma. To investigate the molecular mechanisms of this protection, the effects of 17-β-estradiol on heat shock protein (HSP) expression were studied in normal male and female rats and in male gerbils after global ischemia. 17-β-Estradiol was given intraperitoneally (46 or 460 ng/kg, or 4.6 μg/kg) and Western blots performed for HSPs. 17-β-Estradiol increased hemeoxygenase-1, HSP25/27, and HSP70 in the brain of male and female rats. Six hours after the administration of 17-β-estradiol, hemeoxygenase-1 increased 3.9-fold (460 ng/kg) and 5.4-fold (4.6 μg/kg), HSP25/27 increased 2.1-fold (4.6 μg/kg), and Hsp70 increased 2.3-fold (460 ng/kg). Immunocytochemistry showed that hemeoxygenase-1, HSP25/27,and HSP70 induction was localized to cerebral arteries in male rats, possibly in vascular smooth muscle cells. 17-β-Estradiol was injected intraperitoneally 20 minutes before transient occlusion of both carotids in adult gerbils. Six hours after global cerebral ischemia, 17-β-estradiol (460 ng/kg) increased levels of hemeoxygenase-1 protein 2.4-fold compared with ischemia alone, and HSP25/27 levels increased 1.8-fold compared with ischemia alone. Hemeoxygenase-1 was induced in striatal oligodendrocytes and hippocampal neurons, and HSP25/27 levels increased in striatal astrocytes and hippocampal neurons. Finally, Western blot analysis confirmed that estrogen induced heat shock factor-1, providing a possible mechanism by which estrogen induces HSPs in brain and other tissues. The induction of HSPs may be an important mechanism for estrogen protection against cerebral ischemia and other types of injury.


2012 ◽  
Vol 63 (4) ◽  
pp. 417-427 ◽  
Author(s):  
Mariana Tozlovanu ◽  
Delphine Canadas ◽  
Annie Pfohl-Leszkowicz ◽  
Christine Frenette ◽  
Robert J. Paugh ◽  
...  

AbstractIn the present study the photoreactivity of the fungal carcinogen ochratoxin A (OTA) has been utilised to generate authentic samples of reduced glutathione (GSH) and N-acetylcysteine (NAC) conjugates of the parent toxin. These conjugates, along with the nontoxic OTα, which is generated through hydrolysis of the amide bond of OTA by carboxypeptidase A, were utilised as biomarkers to study the metabolism of OTA in the liver and kidney of male and female Dark Agouti rats. Male rats are more susceptible than female rats to OTA carcinogenesis with the kidney being the target organ. Our studies show that the distribution of OTA in male and female rat kidney is not significantly different. However, the extent of OTA metabolism was greater in male than female rats. Much higher levels of OTα were detected in the liver compared to the kidney, and formation of OTα is a detoxification pathway for OTA. These findings suggest that differences in metabolism between male and female rats could provide an explanation for the higher sensitivity of male rats to OTA toxicity


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