Young Female Rats Research Articles

Abstract WP243: Intraperitoneal Igf1 Treatment Modulates The Chronic Impact Of Ischemic Stroke In Reproductively Senescent Female Rats By Repairing The Gut While Icv-igf-1 Does Not

Background: Our previous studies have shown that reproductively senescent (RS) female rats, who have lower circulating levels of the peptide hormone Insulin-like Growth Factor (IGF-1), display worse outcomes after a stroke event than young adult female rats. ICV administration of IGF-1, decreases infarct volume, improves sensory motor performance, and reduces cytokine levels in the ischemic hemisphere of RS females as compared to vehicle-treated controls. Yet, icv IGF1 administration failed to attenuate peripheral inflammation cognitive decline and depressive behaviors in the chronic phase of stroke. In view of the evidence that stroke induces gut dysbiosis, and that gut dysfunction is implicated in depressive and cognitive behaviors, we hypothesize that, unlike icv administration of IGF-1, which is restricted to the brain, systemic i.p. administration of IGF1 would repair the gut, attenuate peripheral cytokine levels and improve long-term behavior outcomes. Methods: Acyclic middle-aged Sprague Dawley female rats (9-11 mos) were subjected to endothelin-1 induced middle cerebral artery occlusion (MCAo) or sham operation. Animals received IGF1 via i.p. injections 4h post MCAo and 24 h post MCAo, or icv infusions, while controls received vehicle. Sensory motor tests, blood and gut samples were acquired pre and post MCAo. Animals were terminated either in the acute phase (2d) or chronic phase (20d). The latter group was also subject to tests of cognition and depressive-like behavior. Results: In contrast to icv treatment, i.p.-IGF-1 did not reduce infarct volume or acute sensory motor impairment but significantly attenuated circulating levels of TNFα and IL12p70. In addition, ip-IGF-1 significantly attenuated post stroke gut dysmorphology, by preserving villus:crypt ratio and expression of tight junction proteins ZO1 and claudin-2. In addition, i.p. IGF1 treatment attenuated the reduction of social interaction and novel object preference post MCAo. Conclusion: Since long term disability after stroke is correlated with elevated levels of peripheral cytokines, our data suggest that systemic IGF1 may be a better therapeutic option for long term cognitive and depressive behaviors after stroke.

Effects of bisphenol A on pancreas and thyroid gland of young and adult female Sprague Dawlеy rats

Bisphenol A (BPA), a chemical involved in formation of plastic vessels, is one of the most widespread endocrine disrupting chemicals. The study was designed to investigate the effect of BPA on pancreas and thyroid gland of young and adult female Sprague Dawley rats. The rats were exposed to 330 mg/kg BPA orally every other day for 12 weeks; control rats were exposed orally to ethyl alcohol and corn oil. Samples were collected at 4, 8 and 12 weeks for hormonal, biochemical assays and histopathological examination. The insulin hormone in exposed young rats was decreased, but its level in adult ones was increased; the biochemical assay for blood sugar level showed a significant increase in young rats and decrease in adult ones. T3 hormone was increased in treated young and adult rats; T4 hormone was increased in treated adults, while calcium level was decreased in treated adult rats. The histopathological findings of pancreas revealed vacuolation in its endocrine parts in young rats, while in adult ones there was intralobular fatty infiltration - a typical picture of diabetes. The thyroid gland in treated young female rats showed increased cellularity of parafollicular cells; moreover there was parafollicular haemorrhage, and in adult ones - desquamation in lining epithelium of follicular cells. In conclusion, exposure of young and adult female rats to BPA resulted in changes in the pancreatic and thyroid gland cells manifested by morphological, hormonal and biochemical parameters.

Differential effects of a cafeteria diet and GSPE preventive treatments on the enterohormone secretions of aged vs. young female rats.

Grape seed derived procyanidins (GSPE) have been shown to effectively prevent intestinal disarrangements induced by a cafeteria diet in young rats. However, little is known about the effects of procyanidins and cafeteria diet on enterohormone secretion in aged rats, as the ageing processes modify these effects. To study these effects in aged rats, we subjected 21-month-old and young 2-month-old female rats to two sub-chronic preventive GSPE treatments. After three months of cafeteria diet administration, we analysed the basal and stimulated secretion and mRNA expression of CCK, PYY and GLP-1, caecal SCFA and intestinal sizes. We found that the effects of a cafeteria diet on the basal duodenal CCK secretion are age dependent. GLP-1 in the ileum was not modified regardless of the rat's age, and GSPE preventive effects differed in the two age groups. GSPE pre-treatment reduced GLP-1, PYY and ChgA in mRNA in aged ileum tissue, while the cafeteria diet increased these in aged colon. The GSPE treatments only modified low-abundance SCFAs. The cafeteria diet in aged rats increases the caecum size differently from that in young rats and GSPE pre-treatment prevents this increase. Therefore, ageing modifies nutrient sensing, and the cafeteria diet acts mainly on the duodenum and colon, while procyanidins have a larger effect on the ileum.

Melatonin Alleviates Constant Light Induced Oxidative Stress Damages of Kidney and Spleen of Female Rat

Photoperiod refers to the relative duration of light and dark that an animal experiences over the course of a 24 h period. Light is the principal stimulus that causes profound physiological and behavioural changes in all living organism. By manipulating photoperiod, melatonin production changes and its secretion drives enduring changes in many physiological systems of our body. Taking into consideration that light can affect pineal function and melatonin can be used as reactive oxygen species scavenger, act as a potent antioxidant and immunomodulator in mammals, the present experiment was designed and conducted to explore the consequences of constant light exposure on oxidative stress and antioxidant status on kidney and spleen of rat. 16 young adult female rats were randomly divided into 3 groups. The 4 rats of first group were employed as Control. These animals were kept under a 12 h light (600 lux, 60 days)/12 h dark cycle. The 8 rats of second group were maintained under constant light condition (600 lux, 60 days). After 60 days of constant light exposure second group of rats were randomly divided into two. One of these group of rats were designated as constant light exposed rats (LL) and another group of rats exposed to constant light is treated with melatonin (LL+MEL) for 21 days. The 4 rats of third group were only supplemented melatonin (MEL). The results showed that constant light exposure (60 days, 600 lux) resulted in an increased lipid peroxidation rate in kidney and spleen tissue and could effectively disturb the immune cells function through excessive generation of free radicals and decreased antioxidant enzymes activity (superoxide dismutase, catalase, glutathione peroxidase) through physiological or functional pinealectomy. Exogenous melatonin administration (200 µg/100 g body weight/day) suppressed the constant light induced oxidative stress and increase the activity of antioxidant enzymes in kidney and spleen of rat. Hence, melatonin has a nephroprotective and immunoprotective effects following photoperiodic stress induced cellular damages in female rat model.

Capsaicin prevents radiotherapy-induced premature ovarian failure in rats.

Ionising radiation exposure of 5-10gray (Gy) to the pelvic area induces premature ovarian failure (POF). Twenty-four young adult Wistar albino female rats were were treated with subcutaneous capsaicin 0.5mg/kg per day or placebo for 10days then exposed to whole body irradiation. Rats were randomly divided into four groups: (1) control; (2) capsaicin; (3) radiation only (IR): rats were injected with placebo before exposure to a single dose of 8.3-Gy whole body irradiation; (4) radiation-capsaicin (IR+CAP): rats were injected with capsaicin prior to whole body irradiation. Radiation triggered oxidative stress, increased ovarian inflammation, increased follicular apoptosis and diminished ovarian follicle pool. Capsaicin significantly ameliorated oxidative stress by decreasing serum total oxidant status, oxidative stress index, disulphide, and malondialdehyde levels (P ≤0.001); ovarian inflammatory status by decreasing expressions of TNF-α, IL-1β, PARP-1 (P =0.002); apoptosis by decreasing expressions of active caspase-3 and p53 (P =0.015, P =0.002); and follicle counts by increasing primordial follicles and decreasing apoptotic follicles (P ≤0.001) in rats when administered before radiation exposure. The beneficial effects of capsaicin are demonstrated for the first time on ionising radiation exposed rat ovaries. Capsaicin pre-treatment before radiotherapy restores the primordial follicle pool, inhibits atresia of ovarian follicles and may be an acceptable therapeutic modality to prevent radiation-induced POF.

Investigation of the Effects of Cardiovascular Therapeutic Ultrasound Applied in Female and Male Rats' Hearts of Different Ages.

This study investigates the role of age and sex on the cardiovascular effects of 3.5-MHz pulsed ultrasound (US) in a rat model. Ultrasonic bursts of 2.0-MPa peak rarefactional pressure amplitude (equivalent to an in vitro spatial-peak temporal-peak intensity of ~270 W/cm2 and a mechanical index of 1.1) were delivered in five consecutive 10-s intervals, one interval for each pulse repetition frequency (PRF) (6, 5, 4, 5, and 6 Hz; always the same order) for a total exposure duration of 50 consecutive seconds. Sixty F344 rats were split into 12 groups in a 3 × 2 × 2 factorial design (three ages, male versus female, and US application versus control). This study is the first study on US-induced cardiac effects that contains data across three age groups of rats (premenopause, fertile, and postmenopause) to mimic the fertile and nonfertile human window. US was applied transthoracically, while heart rate, stroke volume, ejection fraction, temperature, and other physiologic parameters were recorded at baseline and after exposure. Significant decreases in cardiac output compared to respective control groups were observed in multiple experimental groups, spanning both females and males. A negative chronotropic effect was observed in young male (~7%) and female (~16%) rats, in five-month-old male (~9%) and female (~15%) rats, and in old rats where the effect was not statistically significant. Younger groups and, to a lesser extent, lower weight groups generally had more significant effects. The pathophysiology of US-induced cardiovascular effects appears to be multifactorial and not strictly related to hormones, menopause, weight, sex, or age, individually.

Artificial Intelligence Identified Resilient and Vulnerable Female Rats After Traumatic Stress and Ethanol Exposure: Investigation of Neuropeptide Y Pathway Regulation.

Post-traumatic stress disorder (PTSD) is initiated by traumatic-stress exposure and manifests into a collection of symptoms including increased anxiety, sleep disturbances, enhanced response to triggers, and increased sympathetic nervous system arousal. PTSD is highly co-occurring with alcohol use disorder. Only some individuals experiencing traumatic stress develop PTSD and a subset of individuals with PTSD develop co-occurring alcohol use disorder. To investigate the basis of these individual responses to traumatic stress, single prolonged stress (SPS) a rodent model of traumatic stress was applied to young adult female rats. Individual responses to SPS were characterized by measuring anxiety-like behaviors with open field and elevated plus maze tests. Rats were then allowed to drink ethanol under an intermittent two bottle choice procedure for 8 weeks, and ethanol consumption was measured. An artificial intelligence algorithm was built to predict resilient and vulnerable individuals based on data from anxiety testing and ethanol consumption. This model was implemented in a second cohort of rats that underwent SPS without ethanol drinking to identify resilient and vulnerable individuals for further study. Analysis of neuropeptide Y (NPY) levels and expression of its receptors Y1R and Y2R mRNA in the central nucleus of the amygdala (CeA), basolateral amygdala (BLA), and bed nucleus stria terminalis (BNST) were performed. Results demonstrate that resilient rats had higher expression of Y2R mRNA in the CeA compared with vulnerable and control rats and had higher levels of NPY protein in the BNST compared to controls. The results of the study show that an artificial intelligence algorithm can identify individual differences in response to traumatic stress which can be used to predict subsequent ethanol drinking, and the NPY pathway is differentially altered following traumatic stress exposure in resilient and vulnerable populations. Understanding neurochemical alterations following traumatic-stress exposure is critical in developing prevention strategies for the vulnerable phenotype and will help further development of novel therapeutic approaches for individuals suffering from PTSD and at risk for alcohol use disorder.

Anorexia disrupts glutamate-glutamine homeostasis associated with astroglia in the prefrontal cortex of young female rats

Anorexia nervosa (AN) is an eating disorder characterized by self-starvation and excessive weight loss with a notorious prevalence in young women. The neurobiology of AN is unknown but murine models, like dehydration induced anorexia (DIA), reproduce weight loss and avoidance of food despite its availability. Astrocytes are known to provide homeostatic support to neurons, but it is little explored if anorexia affects this function. In this study, we tested if DIA disrupts glutamate-glutamine homeostasis associated with astrocytes in the prefrontal cortex (PFC) of young female rats. Our results showed that anorexia reduced the redox state, as well as endogenous glutamate and glutamine. These effects correlated with a reduced expression of the glutamate transporters (GLT-1 and GLAST) and glutamine synthetase, all of them are preferentially expressed by astrocytes. Accordingly, the expression of GFAP was reduced. Anorexia reduced the astrocyte density, promoted a de-ramified morphology, and augmented the de-ramified/ramified astrocyte ratio in the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC), but not in the motor cortex (M2). The increase of a de-ramified phenotype correlated with increased expression of vimentin and nestin. Based on these results, we conclude that anorexia disrupts glutamate-glutamine homeostasis and the redox state associated with astrocyte dysfunction.

Moxibustion may delay the aging process of Wistar rats by regulating intestinal microbiota

As one of the important treatments of health care and anti-aging in traditional Chinese medicine (TCM), moxibustion has been proved to have the effects of scavenging free radicals, anti-oxidation, reducing inflammatory reaction, regulating immunity and so on. Recent studies have shown that intestinal microbiota affect the process of aging. The relationship between aging, moxibustion and intestinal microbiota is still unclear. In this study, we explored the effects of moxibustion at Guanyuan (RN4) acupoint on intestinal microbiota, short-chain fatty acids and immunological characteristics of young and elder female Wistar rats to explore the relationship between aging, moxibustion and intestinal microbiota. Six 12-week-old female Wistar rats were young group (Y), and twelve 36-week-old female Wistar rats were randomly divided into elder group (C) and moxibustion group (M). The rats in M group were received mild moxibustion at Guanyuan (RN4) acupoint, 20 min/d for 40 days. The rats in Y group and C group were not given any therapeutic intervention. The results showed that moxibustion increased the abundance of intestinal probiotics (mainly Lactobacillus) and the level of short chain fatty acids, the microcirculation blood flow around Guanyuan (RN4) acupoint was also significantly improved in elder rats. In addition, the expression of MyD88, MAPK, TRAF6, NF-κB in intestinal tissue was down-regulated, and the levels of inflammatory cytokines in intestinal were decreased.

The different role of G-protein-coupled receptor 30 (GPR30) in the interaction effects of marijuana and estradiol on spatial learning and memory at different ages

Some studies suggest that the effect of cannabis on behavior performance depends on the presence of ovarian hormones and the age of use initiation. Estradiol is the main ovarian hormone that can interact with cannabinoids. It has been suggested that cannabinoids exert some of their effects directly through estrogen receptors (ERs). A novel G-protein-coupled receptor (GPR30) was described as mediating estrogen signaling in various cell lines. Since there are few studies on the interaction of cannabis and ovarian hormones on cognitive behaviors, so, this study evaluated the role of GPR30 in the effects of marijuana (M) and estrogen, alone and in combination, on spatial learning and memory of young (non-ovarian(OVX)) and old female rats. Young (5–7 months) and old (22–24 months) female rats received an intraperitoneal injection (i.p) of 17β-estradiol (E2), G1 (GPR30 agonist), and G15 (GPR30 antagonist) every four days, and M (every day), either alone or in combination, for 28 days. One hour after the last injection, the Morris water maze (MWM) test was conducted to evaluate of spatial learning and memory. Moreover, hippocampal BDNF level was assessed by the ELISA method. The results showed a positive effect of M on spatial learning in both young and old rats, however, E2 showed beneficial effects on the memory of young, but not old rats. Our results showed that GPR30 does not have any role in the interaction effects of M and E2 in young rats. Although both E2 and M alone showed positive effects on spatial learning and memory in old rats, however, our results showed a negative interaction between marijuana and E2 combined effects on spatial learning and memory in old female rats which is mediated by GPR30. Our results showed that the effects of GPR30 on spatial learning and memory is age dependent. Furthermore, this study showed that hippocampal BDNF does not have any role in the interaction effects of M and E2 on spatial learning and memory in young and old rats.

Iron deficiency and high-intensity running interval training do not impact femoral or tibial bone in young female rats.

In the USA, as many as 20 % of recruits sustain stress fractures during basic training. In addition, approximately one-third of female recruits develop Fe deficiency upon completion of training. Fe is a cofactor in bone collagen formation and vitamin D activation, thus we hypothesised Fe deficiency may be contributing to altered bone microarchitecture and mechanics during 12-weeks of increased mechanical loading. Three-week old female Sprague Dawley rats were assigned to one of four groups: Fe-adequate sedentary, Fe-deficient sedentary, Fe-adequate exercise and Fe-deficient exercise. Exercise consisted of high-intensity treadmill running (54 min 3×/week). After 12-weeks, serum bone turnover markers, femoral geometry and microarchitecture, mechanical properties and fracture toughnessand tibiae mineral composition and morphometry were measured. Fe deficiency increased the bone resorption markers C-terminal telopeptide type I collagen and tartate-resistant acid phosphatase 5b (TRAcP 5b). In exercised rats, Fe deficiency further increased bone TRAcP 5b, while in Fe-adequate rats, exercise increased the bone formation marker procollagen type I N-terminal propeptide. In the femur, exercise increased cortical thickness and maximum load. In the tibia, Fe deficiency increased the rate of bone formation, mineral apposition and Zn content. These data show that the femur and tibia structure and mechanical properties are not negatively impacted by Fe deficiency despite a decrease in tibiae Fe content and increase in serum bone resorption markers during 12-weeks of high-intensity running in young growing female rats.

Expression of concern to: Effects of growth hormone on bone modeling and remodeling in hypophysectomized young female rats: a bone histomorphometric study.

Expression of concern to: Effects of growth hormone on bone modeling and remodeling in hypophysectomized young female rats: a bone histomorphometric study.

Dissimilar Anxiety-like Behavior in Prepubertal and Young Adult Female Rats on Acute Exposure to Aluminium.

Puberty is a developmental transition in which an estrogenic surge occurs, mediating the release of xenoestrogens, like aluminium. Aluminium's effect on anxiety in rodents at the different developmental stages is inconsistent. This study aimed at investigating the effect of the metalloestrogenic property of aluminium on anxiety-like behavioral changes in prepubertal and young adult female rats. Considering this aim, our objective was to evaluate the anxiety-like behavior by the elevated plus maze in prepubertal and young adult female rats with or without acute exposure to aluminium. To address this property of aluminium, 5mg/Kg body weight (Al-5) and 10 mg/Kg body weight (Al-10) of aluminium was administered intraperitoneally to female rats at two developmental stages, prepubertal (PP; n = 8 for each dose) and young adult (YA; n = 6 for each dose) for two weeks. Post-treatment, three days behavioral assessment of the rats was done employing elevated plus maze. Reduced escape latency was seen in Al-5, Al-10 pre-pubertal rats, and Al-5 young-adult rats on day 3. A significant reduction in open arm time was seen in the Al-5 young-adult rats. Aluminium treatment in the pre-pubertal rats reduced their head dipping and grooming. Reduced sniffing, head dipping, and stretch-attended posture in the treated young-adult female rats showed that they had impaired risk-taking tendency. Differential effect on the anxiety-like behavior in the pre-pubertal and young-adult female rats might be due to the metalloestrogenic property of aluminium, acting differently on the two age groups.

Експериментальна оцінка ембріотоксичних ризиків кадмію хлориду при ізольованому введенні та у поєднанні з солями цитрату і нанокомпозитом на його основі

Cadmium compounds that enter living organisms pose the potential for serious health effects as they exhibit mutagenic, carcinogenic, gonadotoxic, teratogenic, allergenic and embryotoxic effects. It is important to study the mechanisms of their toxic effect on embryonic development and structural and functional formation of organs of living organisms and to search for their bioantogonists. The purpose of the study was to highlight the results of intragastric administration of cadmium chloride (1.0 mg/kg) with isolated administration and in combination with metal citrates (cerium, germanium, zinc, and nanocomposite (iodine + sulfur + selenium citrates)) on the overall course of rat embryogenesis. Materials and methods. For the study, young female Wistar rats weighing 170-200 g were used. They were divided into 6 groups, depending on the test substances, which they received from the 1st to the 19th day of gestation. Results and discussion. The analysis of the results of the experimental study showed the negative effect of cadmium chloride on the analyzed indicators of embryogenesis (preimplantation mortality, postimplantation mortality, total embryonic mortality), indicators of intrauterine survival, morphological (anatomical) malformations, as well as general delay in fetal development), both on the 13th and 20th days of pregnancy relative to the control group. In particular, the indicators of total embryonic mortality significantly increased by 4.2 times (13th day) and 3.7 times (20th day), with significant increase preimplantation mortality by 6.5 times, postimplantation mortality by 3.0 times on the 13th day of embryonic development, and on the 20th day, the preimplantation mortality indicator was by 14.0 times higher (p <0.01), and the postimplantation mortality indicator was insignificantly by 2.5 times higher than the control group. In the groups of the combined effect of cadmium chloride with metal citrates, there was a proven decrease in the indicators of total embryonic mortality (18.18% - 38.10%), preimplantation mortality (21.43% - 53.85%), postimplantation mortality (20.0% - 66.7%), an increase in the number of fetuses per female (12.66% -36.0%). Conclusion. In groups of the combined effect of cadmium chloride with metal citrates, the obtained data indicate a decrease in the accumulation of cadmium under the influence of the studied citrates, which allows them to be considered as potential bioantagonists of cadmium chloride

Effects of Age and Sex on the Healing of Acetic-Acid Induced Ulcerative Colitis in Adult Wistar Rats

Aims: Ulcerative colitis is a disease of the bowel that occurs in all ages and affects both males and females. This research study was designed to investigate the effect of age and sex on the healing of colitis in rats.
 Methodology: Twenty - eight rats were randomly distributed into four groups of seven animals per group; adult male rats, mid age male rats, adult female rats and mid age female rats. Mid age and adult Wistar rats were 7- 8weeks and 14 weeks old respectively. Colitis was induced through a single intra-colonic instillation of 7% acetic acid (1mL/100g body weight) and allowed to heal for 14 days. Blood samples were obtained for analysis. Colon samples were also obtained for histomorphological study and biochemical assays (Myeloperoxidase activities, Superoxide dismutase, Glutathione, Catalase and Malondialdehyde) levels.
 Results: There was no significant difference in Malondialdehyde concentration, catalase, Superoxide dismutase, Myeloperoxidase, Platelet Distribution Width, Platelet Count, Basophil cell numbers, Eosinophil cell numbers, platelet cells, Mean Platelet Volume , Mean Cell Volume and white blood cells across the groups. The Glutathione concentration in mid age male rats was significantly increased when compared with adult male rats. The haemoglobin , Lymphocytes and Mean Cell Haemoglobin levels were increased while neutrophils and monocyte levels were decreased in the younger female rats. The histomorphological study revealed poorly preserved surface epithelia layer of the colon in adult male rats while mid age male and female rats showed moderately preserved surface epithelia layer, adult female rats showed normal surface epithelia layer.
 Conclusion: Mid age rats heal faster than adult rats while in terms of sex, female rats tends to heal faster than male rats.

Creatine Supplementation Upregulates mTORC1 Signaling and Markers of Synaptic Plasticity in the Dentate Gyrus While Ameliorating LPS-Induced Cognitive Impairment in Female Rats.

Mild cognitive impairment (MCI) designates the boundary area between cognitive function in natural aging and dementia, and this is viewed as a therapeutic window to prevent the occurrence of dementia. The current study investigated the neurocognitive effects of oral creatine (Cr) supplementation in young female Wistar rats that received intracerebroventricular injections of lipopolysaccharide (LPS) to mimic MCI. Neuromolecular changes within the dentate gyrus were analyzed following behavioral testing. We also investigated both neurocognitive and neuromolecular changes following Cr supplementation in the absence of LPS in young female Wistar rats to further investigate mechanisms. Interestingly, based on trial 2 of Barnes maze test, Cr supplementation ameliorated spatial learning and memory deficit induced by LPS, shown by decreased latency time and errors to reach the escape box (p < 0.0001, n = 12). Cr supplementation also attenuated recognition memory deficit induced by LPS, shown by increased amount of time taken to explore the new object (p = 0.002, n = 12) during novel object recognition testing. Within the dentate gyrus, Cr supplementation in LPS injected rats upregulated mTORC1 signaling (p = 0.026 for mTOR phosphorylation, p = 0.002 for p70S6K phosphorylation, n = 8) as well as the synapsin (p = 0.008) and PSD-95 synaptic proteins (p = 0.015), in comparisons to LPS injected rats. However, Cr supplementation failed to further enhance spatial memory and recognition memory in the absence of LPS. In conclusion, Cr ameliorates LPS-induced cognitive impairment in a rodent MCI model. Mechanistically, these phenotypic effects may, in part, be mitigated via an upregulation of mTORC1 signaling, and an enhancement in synaptogenesis in the dentate gyrus. While preliminary, these findings may inform future research investigating neurocognitive effects of Cr for MCI patients.

The art of facilitation: a delicate hormonal balance!

The art of facilitation: a delicate hormonal balance!

P–443 Effects of capsaicin pre-treatment on ovarian follicle pool, inflammatory and apoptotic pathways against radiation induced ovarian failure

Abstract Study question Is capsaicin effective in preventing radiation induced ovarian follicle loss and premature ovarian failure (POF) in rats? Summary answer Capsaicin pre-treatment before radiotherapy restores especially primordial follicle pool, inhibits atresia of ovarian follicles, may be an acceptable therapeutic modality to prevent radiation induced POF. What is known already Ionizing radiation exposure to pelvic area induces inflammation, oxidative stress, follicular atresia and apoptosis; leading to POF. Phytochemicals were used in animal studies to prevent radiotherapy induced POF because of their antioxidant and anti-inflammatory properties however their potential radio-protective effects in human ovarian follicles are not clear. Capsaicin is the active compound of hot peppers and has anti-inflammatory and antioxidant properties. It was found that low dose capsaicin stimulated ovarian follicular development and proliferation of granulosa cells, inhibited apoptosis of ovarian follicles in pre-pubertal rat ovaries. However, no data exists on radio-protective effects of capsaicin on ovarian follicles. Study design, size, duration Twenty-four young adult Wistar albino female rats were housed under standard conditions (20 ± 1 0C room temperature, 60 ± 10% humidity, and a 12/12-h light/dark cycle) in regular cages and allowed free access to food and water. After 10 days of subcutaneous capsaicin 0,5 mg/kg/day or placebo treatment, animals exposed to total body irradiation of 8.3 Gy using a linear accelerator. Treatment continued for 1 day after irradiation. Participants/materials, setting, methods Rats were randomly divided into four groups: (1) control: non-irradiated rats were injected placebo; (2) capsaicin: non-irradiated rats were injected capsaicin; (3) radiation only (IR): rats were injected placebo before exposure to a single dose of 8.3-Gy whole body radiation; (4) Radiation-capsaicin (IR+CAP): rats were injected capsaicin prior to whole body irradiation and continued for 1 day after irradiation. Rats were sacrificed, blood samples were obtained for biochemical investigations. Ovaries were dissected for histopathological evaluation. Main results and the role of chance Radiation triggered oxidative stress, increased ovarian inflammation, increased follicular apoptosis and diminished ovarian follicle pool. Capsaicin was significantly ameliorated; oxidative stress by decreasing serum total oxidant status, oxidative stress index, disulfide, and malondialdehyde levels (p ≤ 0.001 both); ovarian inflammatory status by decreasing expressions of TNF-α, IL–1β, poly ADP-ribose polymerase–1 (PARP–1) (p = 0.002 both); apoptosis by decreasing expressions of active caspase–3 and p53 (p = 0.015 and p = 0.002 respectively); follicle counts by increasing primordial follicles and decreasing apoptotic follicles (p ≤ 0.001 both) in rats when administered before radiation exposure. Results of our study confirmed previously reported pro-proliferative and anti-apoptotic properties of capsaicin on ovarian follicles. These beneficial effects of capsaicin are demonstrated for the first time on ionizing radiation exposed rat ovaries. Limitations, reasons for caution Present study is a in-vivo rat study and other preclinical studies are needed to confirm our findings before moving forward to human trials. Radio-protective effects of capsaicin on rat ovarian follicles were demonstrated only in short term. Long term effects of capsaicin on folliculogenesis, fertilization and fecundity should be investigated. Wider implications of the findings: Preserving fertility is one of the main goals of successful radiotherapy in terms of quality of life for oncological or hematological diseases. Capsaicin treatment before radiotherapy may be an acceptable therapeutic modality to prevent radiation induced POF and has potential to utilize in clinical application in terms of fertility preservation. Trial registration number 218S876/2019

Chronic Effect of a Cafeteria Diet and Intensity of Resistance Training on the Circulating Lysophospholipidome in Young Rats.

The daily practice of physical exercise and a balanced diet are recommended to prevent metabolic syndrome (MetS). As MetS is a multifactorial disorder associated with the development of serious diseases, the advancement of comprehensive biomarkers could aid in an accurate diagnosis. In this regard, it is known that gut microbiota is altered in MetS, and especially, lipid metabolites species are highly modified, thus emerging as potential biomarkers. In preliminary studies, we observed that alterations in serum lysoglycerophospholipids (Lyso-PLs) were shared between animals with diet-induced MetS and those performing resistance exercises assiduously. Therefore, our objective was the targeted determination of the lysophospholipidome in young rats fed a standard (ST) or a cafeteria diet (CAF) and submitted to different training intensities to evaluate its potential as a biomarker of a detrimental lifestyle. Targeted metabolomics focused on lysophosphatidylcholines (Lyso-PCs) and lysophosphatidylethanolamines (Lyso-PEs) and multivariate statistics were used to achieve an integral understanding. Chronic intake of CAF altered the serological levels of both lipid subclasses. Twenty-two Lyso-PLs were significantly altered by CAF, from which we selected Lyso-PCs (14:0), (17:1) and (20:2) and Lyso-PEs (18:2) and (18:3) as they were enough to achieve an optimal prediction. The main effect of physical training was decreased Lyso-PEs levels with disparities among training intensities for each diet. We concluded that an examination of the lysophospholipidome reveals the general state of the metabolome in young female rats, especially due to intake of an MetS-inducing diet, thus highlighting the importance of this family of compounds in lipid disorders.

The study of the anti-inflammatory properties of carotenoid liquid extracts on the model of adjuvant-induced inflammation

The search for new anti-inflammatory substances is an important area of pharmacology. Plant carotenoids have many positive biological effects and are of interest as potential anti-inflammatory agents.&#x0D; The aim. To study the anti-inflammatory properties of extractive carotenoids from fruits of Capsicum annuum L. on the model of adjuvant-induced inflammation.&#x0D; Materials and methods. The fruits of Capsicum annuum L. were used as the plant raw material. Carotenoids were obtained by the extractive method. The model of adjuvant-induced inflammation was reproduced in young female rats. The dynamics of changes in the volume of the inflammatory edema and the total number of blood leukocytes were studied.&#x0D; Results and discussion. A decrease in edema in nonspecific inflammation was observed on day 15 during the therapy with carotenoid extracts (Δ1.01±0.08 in treatment group; Δ1.28±0.08 in control group). For specific inflammation, edema reduction when using carotenoids occurred on day 30 (Δ0.047±0.015 in treatment group; Δ0.073±0.012 in control group). A decrease in leukocytosis occurred on days 20 and 30 of the treatment for non-specific and specific inflammation, respectively. The mechanisms of the anti-inflammatory action of carotenoids are presumably associated with the antioxidant effect and the ability to affect the production of pro-inflammatory cytokines.&#x0D; Conclusions. Extractive carotenoids from the fruits of Capsicum annuum L. have the anti-inflammatory activity in the case of adjuvant-induced inflammation. Treatment with Capsicum annuum L. extract reduced inflammatory edema and total leukocyte count