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Introduction: Phytocannabinoids have emerged as a potential alternative treatment option for individuals experiencing persistent pain. However, evidence-based research regarding their clinical utility in both males and females remains incomplete. In addition, it is unknown whether combining readily available cannabinoids with opioids has a synergistic or subadditive effect on pain modulation. To begin to fill this knowledge gap, we investigated the antinociceptive effects of the phytocannabinoid, CBD, either alone or in combination with opioids in male and female C57BL/6J mice. Results: Using the formalin test, our results show that CBD (10 mg/kg, i.p.) treatment evoked antinociception in phase I, but not in phase II, of the formalin test in male mice. However, in female mice, CBD showed no significant antinociceptive effect. In addition, a direct sex comparison showed that CBD evoked a significant increase in nociceptive behaviors in female versus male mice during phase I of the formalin test. Furthermore, we show that CBD (10 mg/kg, i.p.) in combination with low-dose morphine (1 mg/kg, i.p.) was ineffective at eliciting a synergistic antinociceptive response in both male and female mice. Lastly, consistent with previous literature, we showed that females treated with a relatively higher dose of morphine (10 mg/kg, i.p.) displayed a significant increase in the variability of nociceptive behaviors compared to morphine-treated male mice. Conclusion: Overall, our results suggest that CBD treatment may have beneficial antinociceptive effects during the acute phase of persistent pain, but these effects are more beneficial to males than females. We provide further pre-clinical support that treatments geared toward reducing nociceptive behaviors differentially affect males and females.

The cystine/glutamate antiporter system xc− has been identified as the major source of extracellular glutamate in several brain regions as well as a modulator of neuroinflammation, and genetic deletion of its specific subunit xCT (xCT−/−) is protective in mouse models for age-related neurological disorders. However, the previously observed oxidative shift in the plasma cystine/cysteine ratio of adult xCT−/− mice led to the hypothesis that system xc− deletion would negatively affect life- and healthspan. Still, till now the role of system xc− in physiological aging remains unexplored. We therefore studied the effect of xCT deletion on the aging process of mice, with a particular focus on the immune system, hippocampal function, and cognitive aging. We observed that male xCT−/− mice have an extended lifespan, despite an even more increased plasma cystine/cysteine ratio in aged compared to adult mice. This oxidative shift does not negatively impact the general health status of the mice. On the contrary, the age-related priming of the innate immune system, that manifested as increased LPS-induced cytokine levels and hypothermia in xCT+/+ mice, was attenuated in xCT−/− mice. While this was associated with only a very moderate shift towards a more anti-inflammatory state of the aged hippocampus, we observed changes in the hippocampal metabolome that were associated with a preserved hippocampal function and the retention of hippocampus-dependent memory in male aged xCT−/− mice. Targeting system xc− is thus not only a promising strategy to prevent cognitive decline, but also to promote healthy aging.

Females are uniquely sensitive to drugs of abuse at specific points in their reproductive cycle. Females' endogenous opioid system contributes to both reward-related processes and maternally relevant physiological functions, yet less is known about how adolescent opioid exposure impacts females' future behavior, ranging from parental caregiving to opioid preference. The present study explores 2 questions: (a) are there sex differences in response to adolescent oxycodone exposure, spontaneous withdrawal, and oxycodone preference in adulthood, and (b) to what extent does this pregestational opioid exposure alter females' future maternal caregiving behavior? Female and male mice received 12d of oxycodone or saline injections during mid/late adolescence, and drug was then withheld. Some females were then mated and experienced a drug-free pregnancy. Following parturition, females' maternal behavior and motivation were assessed. All mice then underwent a place conditioning procedure to assess the incentive value of oxycodone during adulthood. Mice displayed similar behavioral responses to oxycodone (e.g., sensitization) and patterns of withdrawal behaviors, independent of sex. Mice showed strong group preferences for the oxycodone-paired chamber, and the strength of these preferences did not differ by sex or maternal status. Postpartum females' maternal behavior and motivation were also similar despite adolescent drug history. Together, results did not suggest overt sex differences in response to adolescent oxycodone exposure and that, in females, a range of motivated behaviors may be relatively resilient to such perturbations during adolescence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Introduction: Epilepsy is one of the most common neurological disorders. Though there are several effective drugs for treating epilepsy, most drugs are associated with side effects and drug interactions. Stachys lavandulifolia used in Iranian traditional medicine has proven anti-anxiety and sedative properties. The current study aimed to evaluate the anticonvulsant effect of hydroalcoholic extract of S. lavandulifoliaon the Pentylenetetrazole (PTZ)-induced seizure in male mice and the role of benzodiazepine and opioid receptors. Methods: This study was conducted on 100 male mice, randomly categorized into 10 groups: Normal Saline (NS), two diazepam groups (0.025 and 0.1 mg/kg), three S. lavandulifolia extract groups (50, 100, and 200 mg/kg), diazepam 0.025 mg/kg+S. lavandulifolia extract 50 mg/kg, and three groups that pretreated with NS, flumazenil, or naloxone, 5 min before injection of 200 mg/kg S. lavandulifolia extract. After 30 min, PTZ (80 mg/kg) was injected into animals, and seizure indices were evaluated. Results: The S. lavandulifoliaextract attenuated the PTZ-induced seizures in a dose-dependent manner, and pretreatment with flumazenil reversed this effect. However, pretreatment with naloxone could not reverse this effect because seizure indices in the naloxone pretreated group were lower than that in the normal saline group. The combination of an ineffective dose of diazepam and S. lavandulifoliaextract decreased PTZ-induced seizures. Conclusion: The results of our study showed the anticonvulsant properties of hydroalcoholic extract of S. lavandulifolia. These effects might be due to the impact of the components of this extract on the central benzodiazepine system.

Glioblastoma (GBM) is the most common primary brain cancer in adults where tumor cell heterogeneity and sex differences influence clinical outcomes. Here, we functionally characterize three male and three female patient-derived GBM cell lines, identify protumorigenic BTICs, and create novel male and female preclinical models of GBM. Cell lines were evaluated on the following features: proliferation, stemness, migration, tumorigenesis, clinical characteristics, and sensitivity to radiation, TMZ, rhTNFSF10 (rhTRAIL), and rhBMP4. All cell lines were classified as GBM according to epigenetic subtyping, were heterogenous and functionally distinct from one another, and re-capitulated features of the original patient tumor. In establishing male and female preclinical models, it was found that two male-derived GBM cell lines (QNS108 and QNS120) and one female-derived GBM cell line (QNS315) grew at a faster rate in female mice brains. One male-derived GBM cell line (QNS108) decreased survival in female mice in comparison with male mice. However, no survival differences were observed for mice injected with a female-derived cell line (QNS315). In summary, a panel of six GBM patient-derived cell lines were functionally characterized, and it was shown that BTIC lines can be used to construct sex-specific models with differential phenotypes for additional studies.

Early-life exposure to Δ9-tetrahydrocannabinol (Δ9-THC), the intoxicating constituent of cannabis, may produce enduring neurochemical changes in brain structures involved in the regulation of sociality but it is still unclear how such changes influence social behavior later in life. In the present study, we exposed male mice to moderate daily doses of Δ9-THC (5 mg/kg, intraperitoneal) during adolescence (postnatal day, PND, 30 to 43) and, when animals reached adulthood (PND70), we assessed their performance in the three-chamber social interaction task before and 3 weeks after injection of the chemical irritant formalin (1 % vol, intraplantar), which produces both immediate and persistent pain-related behaviors in mice. Prior Δ9-THC treatment did not alter social interaction in control adult mice but disrupted it in animals that developed lasting sensory abnormalities following formalin injection. The findings suggest that frequent exposure to Δ9-THC during adolescence causes in male mice a dormant dysfunction in social behavior which can be unmasked in adulthood when the animals experience an aversive state.

Gut microbiota balance and metabolites have become a potentially mechanism in maintaining health. The specific aim of this study was to compare the modulation of puerarin and puerarin acid esters on gut microbial composition and metabolites. Male mice were fed a control diet or diets supplemented with puerarin, puerarin propanoate ester, puerarin hexanoate ester, puerarin myristate ester for 24 h, respectively. The result revealed that puerarin acid esters with different chain lengths showed different activities to create more own impacted bacterial. Puerarin propanoate and puerarin hexanoate ester significantly improved the diversity of microbiota and promoted the relative abundance of beneficial gut microbiota such as Lactobacillus, Barnesiella, Clostridium IV, Prevotella. Additionally, the puerarin propanoate ester group showed the capacity to deliver specific propionic acid to the colon. But esters with medium-long chain lengths had more opportunity to alter gut microbiota for enhancing the short chain fatty acids production. As a whole, puerarin acid esters with different chain lengths supplements shaped different gut microbial and short chain fatty acids metabolism, which could improve human health.

Introduction: The aqueous extract of Azanza garckeana was recently reported of exhibiting ameliorative and pro-fertility properties however the protective effects on formalin testicular toxicity have not been studied. Objective: This study investigated the protective effect of methanol extract of Azanza garckeana on formalin-induced testicular toxicity. Methods: Forty male albino mice were randomly divided into 8 groups of 5. Animals in the first group (1) served as control and administered normal saline (1 ml/kg) by the oral route daily for 40 days. In similar manner, animal in groups 2 received formalin (10 mg/kg) by the IP route, while animals in groups 3; 4 and 5 concurrently received formalin (10 mg/kg IP) and extract at doses of 125; 250 and 500 mg/kg respectively by the oral route. Mice in groups 6; 7 and 8 received the extract at doses of 125; 250 and 500 mg/kg respectively. Phytochemical analysis was conducted for each constituent using specific methods. Gonadotropin and sperm analysis were carried out using standard methods. Result: Phytochemical screening revealed the presence of various constituents, but notably flavonoids. Induced-toxicity with formalin and concurrent treatment with extract at doses of 250 and 500 mg/kg from day 20 to 40 caused significant body weight increase compared to baseline (p < 0.05). Similarly, treatment with the extract alone at all doses caused significant increase in body weight from day 20 to 40 (p < 0.05). Treatment with the extract at 250 and 500 mg/kg, caused a significant increase in weight of testes and epididymis compared to control and untreated group (p < 0.05).The extract induced significant increase in gonadotropin levels of animals compared to control and the untreated group (p < 0.05).The extract at 125 mg/kg demonstrated the highest fecundity potential, but there was no any consistent relationship between GSI and fecundity. Conclusion: This investigation was able to establish the protective and pro-fertility potentials of methanol extract of Azanza garckeana.

Supplemental Digital Content is available in the text., Previously, we have shown that male mice exposed to maternal separation and early weaning (MSEW)—a mouse model of early life stress—display increased mean arterial pressure compared with controls when fed a high-fat diet. As the stimulation of sensory nerves from fat has been shown to trigger the adipose afferent reflex, we tested whether MSEW male mice show obesity-associated hypertension via the hyperactivation of this sympathoexcitatory mechanism. After 16 weeks on high-fat diet, MSEW mice displayed increased blood pressure, sympathetic activation, and greater depressor response to an α-adrenergic blocker when compared with controls (P

Diet composition, calories, and fasting times contribute to the maintenance of health. However, the impact of very low-calorie intake (VLCI) achieved with either standard laboratory chow (SD) or a plant-based fasting mimicking diet (FMD) is not fully understood. Here, using middle-aged male mice we show that 5 months of short 4:10 VLCI cycles lead to decreases in both fat and lean mass, accompanied by improved physical performance and glucoregulation, and greater metabolic flexibility independent of diet composition. A long-lasting metabolomic reprograming in serum and liver is observed in mice on VLCI cycles with SD, but not FMD. Further, when challenged with an obesogenic diet, cycles of VLCI do not prevent diet-induced obesity nor do they elicit a long-lasting metabolic memory, despite achieving modest metabolic flexibility. Our results highlight the importance of diet composition in mediating the metabolic benefits of short cycles of VLCI., Understanding the contribution of diet composition, calories and length of fasting in health maintenance is still challenging. Here the authors compare the effects of cycles of intermittent very low calorie intake achieved with a plant-based fasting mimicking diet or standard laboratory chow to provide insights into the role played by diet composition in mediating the metabolic benefits of short cycles of very low-calorie intake in mice.

The use of stamina-enhancing drugs is now increasingly widespread. Continuous use of stamina medication can cause side effects such as insomnia, feeling nervous and emotional. Therefore, it is necessary to look for effective drugs, relatively low side effects, and relatively cheap prices. One of them is to use natural materials such as Tinospora crispa (L.) Hook stems. This study is to find out the tonic effect extract ethanol of Tinospora crispa stem against male mice with the Natatory Exhaustion Method. This research is an experimental study with a posttest matched control group design. Tonic effect test experiments were conducted using the Natatory Exhaustion Method. Test animals as many as 25 mice were divided into 5 groups, group I, II, III has given Tinospora crispa stem ethanol extract (100,200 and 400 mg/kg body weight). Group IV was given 100 mg/kg body weight of caffeine (positive control) and group V given 25 mL/kg body weight of Carboxymethylcellulose sodium 0.5 % (negative control). Test reserved per oral for 14 days. Test showing that administration 100, 200, and 400 mg/kg body weight of Tinospora crispa stem ethanol extract gave tonic effect on male mice. Mann-Whitney tests showed that the administration of Tinospora crispa stem ethanol extract doses of 100, 200, and 400 mg/kg body weight gave a tonic effect on male mice with significant value (p

This study aimed to evaluate the immunological potential of Plantago lanceolata through determination of (total and absolute count of white blood cell, total count of red blood cell and total count of hemoglobin). The results indicated the ability of plant extract to modulate toxic effect of methotrexate on albino mice by enhancing immunity through all tested parameters All this effect due to the presence of chemical active constituents of plant especially (flavonoid and alkaloids).

Cannabis sativa is a millenary medicinal plant. However, contrary to worldwide paradigm-shifting, countries like Brazil still prohibit C. sativa cultivation and its medicinal use, even though many populations use aerial parts and roots of this plant for healthcare. As such, the objective of this work was to identify substances in the samples of the C. sativa roots, tracing a correlation with antitussive and expectorant effects. Therefore, samples of C. sativa roots were donated by the Polícia Federal Brasileira, and its aqueous extract (AECsR) was prepared with subsequent lyophilization, to maintain the material stability. After that, the material was analyzed by LC-MS to observe its chemical profile. Four samples (AECsR-A, B, C, and D) were tested in animal models of citric acid-induced cough (0.4 M) and phenol red expectoration (500 mg/kg). Using LC-MS it was possible to identify 5 molecules in C. sativa roots: p-coumaroyltyramine, tetrahydrocannabinol-C4, feruoiltyramine, anhydrocanabisativine, and cannabisativine. In experimental protocols, male mice (Mus musculus) were treated with samples of AECsR at doses of 12.5, 25, or 50 mg/kg regardless of the pharmacological test. In these tests, all samples showed the potential to treat cough and promote fluid expectoration, differing only in the dose at which these effects were observed. Therefore, the data showed that the C. sativa roots of the Brazilian Northeast showed antitussive and expectorant effects, even with intense secondary metabolitesʼ variation, which alters its potency, but not its effect. This highlights the importance of this medicinal plant for future therapy and corroborates to traditional use.

Objectives Osteoarthritis is a painful joint disease responsible for walking impairment. Its quantitative assessment by gait analysis in mice may be a relevant and noninvasive strategy to assess the disease severity. In this study, we aimed to determine the severity of osteoarthritis at the tissular and gait levels in unilateral and bilateral posttraumatic murine osteoarthritis. Methods Twenty-four C57BL/6 male mice were randomly assigned to 3 groups ( n = 8/group): controls, unilateral surgery, and bilateral surgery. Posttraumatic osteoarthritis was induced unilaterally or bilaterally by destabilization of the medial meniscus. Gait analysis was performed weekly with the CatWalkTM XT system until the 16th week after surgery. After animal sacrifices, histological and micro–computed tomographic assessment was performed. Results Operated knees showed a significant increase in the histological score compared with controls ( P < 0.001). Calcified anterior medial meniscal bone volume was higher on the ipsilateral side after unilateral destabilization of the medial meniscus ( P < 0.001) and on both sides after bilateral intervention ( P < 0.01). One week after surgery, the mice mean speed decreased significantly in both operated groups ( P < 0.001 and P < 0.05). In the unilateral group, a significant increase in the contralateral hind print area appeared from week 4 to week 16. Conclusions While bilateral destabilization of the medial meniscus induced no detectable gait modification except 1 week after surgery, unilateral model was responsible for a gait disturbance on the contralateral side. Further studies are needed to better define the place of the CatWalkTM in the evaluation of mouse models of osteoarthritis.

Analgesik obat yang digunakan untuk mengurangi dan menghilangkan rasa sakit tanpa hilang kesadaran. Tumbuhan yang digunakan sebagai analgesik adalah tumbuhan daun kelor (Moringae Oliferae L.) dan daun belimbing wuluh (Averrhoa Bilimbi L.), karena kedua tanaman tersebut menunjukkan adanya senyawa seperti flavonoid, alkaloid, saponin, dan tanin. Tujuan penelitian adalah mengetahui efek analgesik. Pada daun kelor dan daun belimbing wuluh mencit jantan Swiss Webster, dosis gabungan 2:2 dan dosis 800 mg ekstrak Moringa oleifera dan 1000 mg ekstrak daun belimbing wuluh dikurangi pada masing-masing tikus. Metode digunakan untuk menguji aktivitas analgesik adalah metode hot plate. Respon mencit sebelum pemberian dan 0, 15, 30, 45, dan 60 menit setelah pemberian diamati, dan data dianalisis dengan uji ANOVA dan LSD. Ekstrak daun kelor dan daun belimbing wuluh pada dosis kombinasi 1:1, 2:2, 2:1 ada efek analgesik pada mencit jantan galur Swiss Webster jantan. Tiga kombinasi terbaik yang memberikan efek analgesik yaitu pada kombinasi dosis 2:2 dan dosis 800mg dan 1000mg, rata-rata hasil proteksi tarik yang diperoleh adalah 0%, 65; 06%, 13; 65%, -15,29 %, 18; 33%.

We investigated the effect of resveratrol on reproductive toxicity induced by Bisphenol A (BPA) in male mice. Forty mice were randomly classified into five groups: Control; Bisphenol A; Bisphenol A...

A suboptimal blood vitamin C (ascorbate) level increases the risk of several chronic diseases. However, the detection of hypovitaminosis C is not a simple task, as ascorbate is unstable in blood samples. In this study, we examined the serum proteome of mice lacking the gulonolactone oxidase (Gulo) required for the ascorbate biosynthesis. Gulo-/- mice were supplemented with different concentrations of ascorbate in drinking water, and serum was collected to identify proteins correlating with serum ascorbate levels using an unbiased label-free liquid chromatography-tandem mass spectrometry global quantitative proteomic approach. Parallel reaction monitoring was performed to validate the correlations. We uncovered that the serum proteome profiles differ significantly between male and female mice. Also, unlike Gulo-/- males, a four-week ascorbate treatment did not entirely re-establish the serum proteome profile of ascorbate-deficient Gulo-/- females to the optimal profile exhibited by Gulo-/- females that never experienced an ascorbate deficiency. Finally, the serum proteins involved in retinoid metabolism, cholesterol, and lipid transport were similarly affected by ascorbate levels in males and females. In contrast, the proteins regulating serum peptidases and the protein of the acute phase response were different between males and females. These proteins are potential biomarkers correlating with blood ascorbate levels and require further study in standard clinical settings. The complete proteomics data set generated in this study has been deposited to the public repository ProteomeXchange with the data set identifier: PXD027019.

Growth hormone receptor knockout (GHRKO) mice are smaller, long living, and have an increased metabolic rate compared with normal (N) littermates. However, it is known that thermoneutral conditions (30–32°C) elicit metabolic adaptations in mice, increasing the metabolic rate. Therefore, we hypothesized that environmental temperature would affect the expression profile of different adipose tissue depots in GHRKO mice. For this, N (n = 12) and GHRKO (n = 11) male mice were maintained at 23 or 30°C from weaning until 11 months of age. RNA sequencing from adipose tissue depots (epididymal—eWAT, perirenal—pWAT, subcutaneous—sWAT, and brown fat—BAT) was performed. Thermoneutrality increased body weight gain in GHRKO mice, but not in N mice. Only a few genes were commonly regulated by temperature in N and GHRKO mice. The BAT was the most responsive to changes in temperature in both N and GHRKO mice. BAT Ucp1 and Ucp3 expression were decreased to a similar extent in both N and GHRKO mice under thermoneutrality. In contrast, eWAT was mostly unresponsive to changes in temperature. The response to thermoneutrality in GHRKO mice was most divergent from N mice in sWAT. Relative weight of sWAT was almost 4 times greater in GHRKO mice. Very few genes were regulated in N mice sWAT when compared with GHRKO mice. This suggests that this WAT depot has a central role in the adaptation of GHRKO mice to changes in temperature.

Courtship songs in mice have been investigated to understand the mechanisms and ecological relevance of vocal communication. There is evidence that courtship song characteristics vary between individuals from different genetic backgrounds, but little is known about whether individuals, even within the same strain, differ consistently from each other in the syntactical composition and complexity of their songs. In a first confirmatory experiment, we aimed to systematically identify syntactical features typical of songs from different mouse strains, by assessing the composition and complexity (i.e. entropy) of the syntax (i.e. how the different syllables are organized within a song) of male laboratory mice from four different strains (Mus musculus f. domestica: C57BL/6J, BALB/c, DBA/2 and B6D2F1). Mice were individually presented with a swab containing fresh female urine for 5 min to elicit courtship songs. The four strains differed not only in the composition but also in the complexity of their syntax. In a second experiment, we investigated repeatability over time as a marker of individuality as well as the occurrence of recurring motifs (i.e. identical sets of syllables that are repeated within a song) of BALB/c and DBA/2 mice. The same procedure as in the first experiment was followed, but in addition testing was repeated weekly over 3 weeks. In both strains, most syllable types showed moderate to high repeatability, indicating individuality in song syntax. However, a descriptive hierarchical cluster analysis indicated remarkable variability in how similar the syntaxes of songs from the same individual were over time. Furthermore, individuals varied in the expression of recurring motifs. Our study shows that not only the genetic background but also individuality can affect variability in courtship songs in mice. Together, these findings raise intriguing questions on whether different individual singing strategies exist during courtship.

Background: This study aimed to identify the effect of using the Immune Max dietary supplement on the histological composition of some organs in male albino mice. Methods: The study was conducted on the Swiss albino male mice which were divided into two groups: treated group with 0.162 mg/kg/ day of Immune Max and second group as a control. Results: Histological examination was conducted for liver, kidney and spleen. The results showed some histological changes in these organs like loses of tissues, congestion, leukocytes infiltration and dead cells. Conclusion: The purpose of a conclusion that the use of the Immune Max nutritional supplement can cause damage to the tissues of a number of organs and this is likely to be due to the dose concentration and the duration of the treatment. How to cite this article:Jawad MA, Kadhim AJ, Hasan SY. The Effect of Immune Max in the Liver, Kidney and Spleen Histological Structure in Male Albino Mice. J Commun Dis. 2021;53(3):186-189. DOI: https://doi.org/10.24321/0019.5138.202156

Introduction: Stress is the body's reaction to pressure from stressors; one of the stressors that can trigger stress is a noise stressor. Stress can disrupt the body's homeostasis system, one of the cycles of spermatogenesis. Murottal Al-Qur'an therapy listening can produce a response of relaxation and peace of mind to increase healing. Methods: The study was conducted on 25 healthy male mice aged 8-12 weeks grouped randomly into five groups. The positive control group is the normal group. The negative control group is given a 12-hour stressor. The treatment groups are given 12 hours and 1, 2, and 4 hours therapy. The treatment for each group was carried out for 21 days. Spermatogenesis of mice was observed through the number of primary spermatocytes cells and spermatid cells. It takes place during the preparation of testicular histology with Hematoxylin Eosin staining. Primary spermatocyte and spermatid counts were examined under a 40x magnification microscope. Results: Murottal Al-Qur'an therapy can affect the amount of primary spermatocyte cells (p-value = 0.000) and spermatids (p-value = 0,000) that are very significant. Conclusion: Murottal Al-Qur'an therapy can be used to increase the spermatogenesis of mice with stress. Keywords: Stress, Noise, Spermatogenesis, Murottal Al-Qur'an.

Purpose Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome (H-ARS) and delayed effects of acute radiation exposure (DEARE). There is no radiation medical countermeasure approved by the U.S. Food and Drug Administration which can be used prior to radiation exposure to protect exposed individuals. Different formulations containing synthetic genistein (BIO 300) are being developed to counter the harmful effects of radiation exposure. Materials and methods We investigated the efficacy of a BIO 300 Oral Powder (OP) formulation as a prophylactic radiation medical countermeasure against a lethal dose of cobalt-60 gamma-radiation in CD2F1 male mice while comparing to other formulations of BIO 300 and Neulasta (PEGylated filgrastim), a standard of care drug for H-ARS. Results BIO 300 OP provided significant radioprotection against ionizing radiation in mice when administered twice per day for six days prior to total-body radiation exposure. Its radioprotective efficacy in the murine model was comparable to the efficacy of a single subcutaneous (sc) injection of Neulasta administered after total-body radiation exposure. Conclusions Our results demonstrate that BIO 300 OP, which can be administered orally, is a promising prophylactic radiation countermeasure for H-ARS.

Backgrounds and objectives. The wide use of paracetamol at high doses was found to alter sperm parameters especially sperm morphology, and thus its fertilizing capability. Therefore, the present study was designed to use different doses of paracetamol to identify its effect on sperm parameters and testosterone levels in adult male mice. Methods. Forty adult male albino mice were divided into four equal groups, the first group injected with distilled water, the three treated groups injected with different doses of paracetamol (20, 40, 80 mg/kg body weight /day) over a period of 42 days. All doses were given once daily via intraperitoneal injection. Results. The results showed that paracetamol causes a significant decrease in body weight, non-significance effect on sperm parameters at doses of 20 and 40 mg/kg, while it led to a significant effect on sperm parameters at a dose of 80 mg/kg. Also, there was no difference in testosterone level between control and the treated groups (20 and 40mg/kg). But it showed a significant decrease in testosterone level at dose 80 mg/kg treated groups. Conclusion. It is considered safe to use paracetamol at doses 20 and 40 mg/kg but the dose 80 mg/kg has adverse effects on sperm parameters and testosterone level.

Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.

Background Acute intoxication caused by binge ethanol drinking is linked to widespread impairments in brain functions. Various alcohol administration paradigms have been used in animals to model the heterogeneous clinical manifestation of intoxication in people. It is challenging to model a procedure that produces “visible intoxication” in rodents; however, manipulation of variables such as route of alcohol administration, time of availability, frequency, and duration and amount of ethanol exposure has achieved some success. In the current study, we employed a modified drinking-in-the-dark model to assess the validity of this model in producing “post-ethanol consumption intoxication” impairments following prolonged repeated daily voluntary “binge” ethanol consumption. Methods Adult male C57BL/6J mice were allowed a daily 3-h access to non-alcoholic plain or ethanol-containing gel during the dark cycle for a total of 83 days. After the initial 2-month daily DID, ethanol intake patterns were intensely characterized during the next 3 weeks. Immediately following the last DID session (day 83), plain and ethanol gel-consuming mice were then subjected to behavioral tests of locomotor ability and/or anxiety (cylinder, wire grip, open field) followed by blood ethanol concentration measurement. Result Mice exhibited a relatively consistent ethanol consumption pattern during and across daily access periods. Ethanol intake of individual mice positively correlated with blood ethanol concentration that averaged 61.64 ± 2.84 mg/dL (n = 12). Compared to the plain gel-consuming control mice, ethanol gel mice exhibited significant locomotor impairment as well as anxiety-like behavior, with the magnitude of impairments of key indices well correlated with blood ethanol levels. Conclusion The gelatin vehicle-based voluntary ethanol drinking-in-the-dark model reliably produced post consumption acute movement impairments as well as anxiety-like behaviors even after 2 months of daily binge ethanol consumption in male mice. Taken together, this mouse binge ethanol model should facilitate the investigation of mechanisms of binge drinking in subjects chronically abusing ethanol and the search for effective novel treatment strategies.

Background: Antioxidant drugs may be useful in preventing morphine-induced dependency bysuppressing oxidative stress. Vitamin E which has many essential roles in the body is a powerfulantioxidant. On the other hand, selenium is an essential trace element that plays a strong rolein various biochemical pathways. The aim of this study was to investigate the effects of sodiumselenite and vitamin E on morphine-induced dependency in mice. Methods: Ninety male mice, weighing 20 to 30 g, were randomly divided into 10 groups and weretreated as follows: a) saline and b) morphine groups were pretreated (for 2 days) with normalsaline (10 ml.kg-1.day-1, ip) then daily doses of normal saline (10 ml.kg-1.day-1, ip) and morphine(50 mg.kg-1.day-1) were added to the injections for the following 4 days, respectively. c, d, e)sodium selenite, f, g, h) vitamin E, i) vitamin E solvent (almond oil) and j) co-administrationgroups were pretreated (for 2 days) with sodium selenite (0.25, 0.5, 1 mg.kg-1.day-1, ip), vitaminE (20, 40, 60 IU.kg-1.day-1, ip), vitamin E solvent (10 ml.kg-1.day-1, ip) and combination of thedrugs respectively, then morphine doses (50 mg.kg-1.day-1, ip) were added to the injections forthe following 4 days. Withdrawal symptoms were evaluated after injecting naloxone (4 mg/kg/day). Biochemical evaluations were also performed. Results: The results showed that co-administration of sodium selenite and vitamin E (at lowdoses) significantly reduced morphine dependency (p < 0.05). Conclusion: The synergistic effect of sodium selenite and vitamin E can be a suitable andefficient approach to reduce dependency.

Aging is the most important risk factor for cardiovascular diseases. Although exercise is known to be beneficial for the health of aging heart, the optimal exercise training intensity to prevent natural aging-induced cardiac damage has not been defined. In this study, we used 32-week-old male mice and randomly divided them into three groups, namely, untrained (UNT) mice, moderate-intensity exercise training (MET) mice, and high-intensity interval training (HIIT) mice. Mice in the two exercise training groups were subjected to exercise 5 days per week for 24 consecutive weeks. Metabolic characteristics, cardiac function and morphology, myocardial remodeling, myocardial fibrosis (collagen III, α-SMA, and TGF-β), oxidative stress (NRF2, HO-1, SOD, and NOX4), and apoptosis (BAX, Bak, Bcl-2, and Bcl-XL) were analyzed 24 weeks after the different treatments. MET improved cardiac function and reduced myocardial remodeling, myocardial fibrosis, and oxidative stress in the aging heart. MET treatment exerted an anti-apoptotic effect in the heart of the aging mice. Importantly, HIIT did not protect against cardiac damage during the natural aging process. These findings suggest that MET may be one of the main methods to prevent cardiac damage induced by natural aging.

Obesity becomes a global epidemic nowadays. The high-fat diet is used as an alternative therapy for obesity. The optimal composition of a high-fat diet to reduce body weight is still unknown. This study aimed to determine which components of a high-fat diet can decrease body weight, visceral fat, and PPARG expression of visceral fat. This study was conducted at the Faculty of Veterinary Medicine, Universitas Airlangga, for three months by using a randomized post-test only control group design. Fifty male mice, 2-3 months old, 18-30 grams were adapted for one week given standard diet AIN93-M, then mice were divided into five groups, namely K1 (control group, 12% fat, 20% protein, 62% carbs); K2 (30% fat, 60% proteins, 0% carbs); K3 (45% fat, 45% protein, 0% carbs); K4 (60% fat, 30% protein, 0% carbs); and K5 (75% fat, 15% protein, 0% carbs). Bodyweight was measured before and after treatment, then the visceral fat and PPARG expressions were evaluated. Statistical comparisons were performed using Statistical Package for the Social Sciences (SPSS) software. After treatment, there were forty-three mice. The body weight and visceral fat weight of the mice with a high-fat diet were decreased. The most significant changes in body weight were in K4 with -9,60 ± 3,806 grams reduction. The bodyweight of mice in K5, slightly increased than K2-K4. This could be caused by the hormesis phenomenon. PPARG expressions decreased in groups with a high-fat diet but increased in K5. The composition of a high-fat diet in group K4 was the most optimal to decrease the body weight, visceral fat, and PPARG expressions in mice

Cordyceps cicadae, an entomopathogenic fungus, is a source of traditional Chinese medicine in China. Due to the low yield of wild C. cicadae, artificial cultivation approaches will be needed to meet the increasing market demand. Using bioreactor culture can increase mass production and the abundance of the active component, N6‐(2‐hydroxyethyl)‐adenosine (HEA). Here, we describe a safety assessment for a novel mycelium preparation method. Many studies have confirmed the safety of C. cicadae mycelia. However, the acute safety pharmacology of the C. cicadae enriched with the high HEA (3.90 mg/g) compound has not been evaluated. This study evaluated the central nervous system (CNS), cardiovascular system, and respiratory system in ICR male mice via oral gavage administration. For each requested item, two batches of eight mice tested on a vehicle (0.5% carboxymethyl cellulose, CMC) and C. cicadae mycelia (1,000 mg/kg) were performed. The heart rate at 60 min for the vehicle and C. cicadae mycelium treatment was 700.3 ± 55.4 and 603.0 ± 42.3 bpm, respectively (p = .4279). For echocardiographic analysis, the LV mass of the vehicle and drug treatment was 86.7 ± 6.4 and 80.2 ± 7.7, respectively (p = .0933). In the respiratory test, the tidal volume of the vehicle and drug treatments was 0.11 ± 0.01 and 0.14 ± 0.01 at 60 min, respectively (p = .4262). These results demonstrate that the oral administration of HEA‐enriched C. cicadae mycelia is safe for the CNS, cardiovascular, and respiratory systems.

Current literature details an array of contradictory results regarding the effect of radiofrequency electromagnetic radiation (RF-EMR) on health, both in humans and in animal models. The present study was designed to ascertain the conflicting data published regarding the possible impact of cellular exposure (radiation) on male and female mice as far as spatial memory, anxiety, and general well-being is concerned. To increase the likelihood of identifying possible “subtle” effects, we chose to test it in already cognitively impaired (following mild traumatic brain injury; mTBI) mice. Exposure to cellular radiation by itself had no significant impact on anxiety levels or spatial/visual memory in mice. When examining the dual impact of mTBI and cellular radiation on anxiety, no differences were found in the anxiety-like behavior as seen at the elevated plus maze (EPM). When exposed to both mTBI and cellular radiation, our results show improvement of visual memory impairment in both female and male mice, but worsening of the spatial memory of female mice. These results do not allow for a decisive conclusion regarding the possible hazards of cellular radiation on brain function in mice, and the mTBI did not facilitate identification of subtle effects by augmenting them.

Due to its wide usage and recent detection in environmental matrices, hexafluoropropylene oxide dimer acid (HFPO-DA, commercial name GenX) has attracted considerable attention. Here, we explored and compared the toxicity of GenX and its novel analogs with that of perfluorooctanoic acid (PFOA) to provide guidance on the structural design and optimization of novel alternatives to poly- and perfluoroalkyl substances (PFASs). Adult male BALB/c mice were continuously exposed to PFOA, GenX, perfluoro-2-methyl-3,6-dioxo-heptanoic acid (PFMO2HpA), and perfluoro-2-methyl-3,6,8-trioxo-nonanoic acid (PFMO3NA; 0, 0.4, 2, or 10 mg/kg/d) via oral gavage for 28 days. The PFOA, GenX, and PFMO3NA treatment groups showed an increase in relative liver weight, and bile acid metabolism was the most significantly affected pathway in all treatment groups, as shown via weighted gene coexpression network analysis. The highest total bile acid levels were observed in the 2 and 10 mg/kg/d PFMO3NA groups. The ratios of primary bile acids to all bile acids increased in the high-dose groups, while the ratios of secondary bile acids showed a downward trend. Thus, bile acid metabolism disorder may be a prominent adverse effect induced by exposure to GenX, its analogs, and PFOA. Results also showed that the hepatotoxicity of PFMO2HpA was lower than that of GenX, whereas the hepatotoxicity of PFMO3NA was stronger, suggesting that PFMO2HpA may be a potential alternative to GenX.

Biotherapics employed to treat mice infected by Trypanosoma cruzi were carried out with encouraging results. The aim of this study was evaluated the effect of biotherapic of Trypanosoma cruzi 200dH, using two different schedules of treatment. Swiss male mice, aged 56 days-old were infected intraperitonealy with 1,400 blood trypomastigotes of Trypanosoma cruzi Y strain and were divided into groups: C.I.- infected animals, E.D. – Infected animals treated from the day 1 until the end of the experiment; 200dH S.D. – Infected animals treated on the day 1. Parasitological, clinical and immunological parameters were evaluated. The group of animals that received the medicine in a single dose presented higher value to total parasitaemia and lower value of pre patent period compared to control untreated group (p

The development of new and effective pain medications that are natural is expected to have the benefits of treatment. The purpose of this study was to determine the antinociceptive effectiveness of a combination of 75% ethanol extract from dandang gendis leaves and 96% ethanol fraction of bakung leaf. In this study was used chemical method induction (Sigmund's method) in 25 male mice which were divided into 5 treatment groups, namely treatment group I as negative control was given CMC 0.5%, treatment group II as positive control was given acetosal 100 mg / kg BW, treatment groups III, IV and V were given combinations extract. Each group was given treatment orally, thirty minutes then induced with 0.6% acetic acid intraperitonially, after which it was observed and counted for the amount of stretching for sixty minutes. Data were analyzed by one-way ANOVA test. The results of this study showed that all treatment groups had a significant difference (p

With the continuous popularization of smart medicine, the protective effect of silibinin in the liver has attracted much attention. This study mainly explores the liver protection mechanism and absorption promotion technology of silybin based on intelligent medical analysis. Refining of silibinin: accurately weigh 1.0 g of silibinin in a three-necked flask; gradually add 50 mL of anhydrous methanol, reflux and filter the precipitated solid; and weigh it after drying. ICR male mice were taken as experimental subjects and randomly divided into groups of 10 each. The mice in the normal group and the model group were given intragastrically with 0.5% CMC-Na solution; the mice in the silibinin group were given intragastrically with SB/CMC-Na suspension; the mice in the remaining groups were given low, medium, and high-dose suspensions to their stomachs, and silibinin 23 acylate/CMC-Na suspension was administered at a dose of 10 mL/kg for 7 consecutive days. After that, the mice were fasted for 12 hours. After 6 hours of fasting (18 hours after modeling), the blood cells from their orbits were taken, placed in a 37°C water bath for 30 minutes, and centrifuged at 4000 rpm for 10 minutes, and then the serum was taken; the activity equivalent of AST and ALT in serum was measured; serum determination Medium AST and ALT vitality. The mice were killed by decapitation, fresh liver tissue was immediately collected, and part of it was frozen in liquid nitrogen for the RT-PCR test. The hepatocyte expansion and death were observed using a transmission electron microscope, and the oncosis index (OI) was calculated. Another part of the liver tissue was fixed in 4% paraformaldehyde solution, embedded in paraffin, dehydrated, and sliced at 4 μm. Some sections were stained with conventional HE, and the pathological changes of liver cells were observed under light microscope; some sections were subjected to immunohistochemistry. Only one mouse died when 240 mg/kg of silibinin was given 10 minutes after the model was modeled. However, when 240 mg/kg silibinin was given to the mice 20 minutes after modeling, the mortality rate of the mice rose to 50%, and the therapeutic effect was significantly weakened. This research is helpful to advance the research of silybin in liver protection.

The space radiation environment consists of multiple species of charged particles, including 28Si ions, that may impact brain function during and following missions. To develop biomarkers of the space radiation response, BALB/c and C3H female and male mice and their F2 hybrid progeny were irradiated with 28Si ions (350 MeV/n, 0.2 Gy) and tested for behavioral and cognitive performance 1, 6, and 12 months following irradiation. The plasma of the mice was collected for analysis of miRNA levels. Select pertinent brain regions were dissected for lipidomic analyses and analyses of levels of select biomarkers shown to be sensitive to effects of space radiation in previous studies. There were associations between lipids in select brain regions, plasma miRNA, and cognitive measures and behavioral following 28Si ion irradiation. Different but overlapping sets of miRNAs in plasma were found to be associated with cognitive measures and behavioral in sham and irradiated mice at the three time points. The radiation condition revealed pathways involved in neurodegenerative conditions and cancers. Levels of the dendritic marker MAP2 in the cortex were higher in irradiated than sham-irradiated mice at middle age, which might be part of a compensatory response. Relationships were also revealed with CD68 in miRNAs in an anatomical distinct fashion, suggesting that distinct miRNAs modulate neuroinflammation in different brain regions. The associations between lipids in selected brain regions, plasma miRNA, and behavioral and cognitive measures following 28Si ion irradiation could be used for the development of biomarker of the space radiation response.

Introduction: The present study deals with the effect of Nectaroscordum koelzi fruit extract on acute and chronic inflammation. Methods: A total of 84 NMRI mice were used in this study. The effect of the extract on acute inflammation was analyzed by increasing vascular permeability via acetic acid and xylene induced ear edema among mice. The extract was evaluated in terms of effects on chronic inflammation by means of the cotton pellet test among mice. For the assessment of inflammation degree, the mice paw edema volume was measured by the plethysmometric test. Results: The findings showed that the extract was effective on acute inflammation induced by acetic acid in mice. In the xylene ear edema, N. koelzi extract indicated a significant activity in mice. In the cotton pellet method, the methanol extract produced a significant reduction in comparison with the control and dexamethasone. Mice paw edema volume decreased with the extract. Conclusion: In general, the data from the experiments indicated that the methanol extract of N. koelzi has an anti-inflammatory effect on acute and chronic inflammation. However, the exact contributing mechanisms have not been investigated for the pharmacological effects.

Type I platelet-activating factor-acetylhydrolase (PAF-AH) forms a complex consisting of two catalytic subunits (α1 and/or α2) with a regulatory subunit (β). Although this protein was discovered as an enzyme that degrades an acetyl ester linked at the sn-2 position of platelet-activating factor (PAF), its physiological function remains unknown. In this study, to examine whether knockout mice lacking the catalytic subunits of this enzyme showed a different phenotype from that of wild-type mice, we measured and compared the body weights of knockout mice and control mice. The body weights of knockout mice were significantly increased compared to those of the control mice during 6 to 20 weeks from birth. Food intake was also significantly increased in knockout mice compared with control mice during these periods. Since a decrease in testis weight was reported in the knockout mice, we expected a decrease in testosterone levels. We measured and compared the amounts of testosterone in the serum and testis of knockout and control mice using liquid chromatography-tandem mass spectrometry, and found that testosterone levels in both the serum and testis were significantly decreased in the knockout mice compared with the control mice. These results suggest that a deficiency of type I PAF-AH catalytic subunits causes an increase in body weight, in part, due to reduced testosterone levels in male mice.

Background: Regarding the chronic nature of epilepsy, and drug resistance in many cases, herbal medicine has received remarkable interest. Objective The present study aimed to determine the anticonvulsant effects of hydro-alcoholic extract of Ocimum basilicum green leaf on Pentylenetetrazole (PTZ)-induced seizure in male mice. Methods: In this experimental study, 48 albino male mice, weighing 20-25 g were randomly divided into 6 groups. All study groups were injected intraperitoneally (IP). The negative and positive control groups received saline (10 mL/kg) and phenobarbital (40 mg/kg) respectively. The treatment groups received 100, 300, 500, and 1000 mg/kg doses of hydro-alcoholic extract Ocimum basilicum green leaf. To provoke convulsion, after 45 minutes, PTZ was injected (80 mg/kg) to all research groups; accordingly, the d initiation time of myoclonic and tonic-clonic seizures and the frequency of 24h death were measured. Results: The obtained results indicated that the extract delayed the initiation time of myoclonic and tonic-clonic seizures, compared with the controls. The delay was significant at doses of 1000 (P

Objectives Nonalcoholic fatty liver disease (NAFLD) is exceptionally common around the world. The development of NAFLD is increasing rapidly in the world, along with changes in lifestyle. Excess lipid intake is one of the risk factors for NAFLD. The NAFLD model is induced by a high-fat diet contains SFA, MUFA, and ῳ-6 PUFA. This study aims to assess the effect of high-fat diet variation on liver histology in developing NAFLD models in mice. Methods Thirty-six male mice (Balb/c) were divided into six groups fed a high-fat diet containing beef tallow 60%, beef tallow 45%, vegetable ghee, animal ghee + corn oil, vegetable ghee + corn oil for 28 days and compared to a control group fed a chow diet. All of the mice were fed with a high-fat diet in the form of pellets ad libitum for 28 days. Bodyweight and food intake were measured every day. At the last day of treatment, animals were sacrificed and the Liver were taken for histological analysis. Results This study showed that NAFLD model development was achieved in all group mice fed a high-fat diet with different degrees of NAFLD. Beef tallow 60% had the worst liver histology. Conclusions Thus, based on this study, we found that high-fat diet variations influenced the development of NAFLD models in mice, particularly concerning liver histology.

Colorectal carcinogenesis is characterized by oxidative stress and the formation of aberrant crypts in its initial stages. Gum arabic (GA) is a natural product with antioxidant properties, and, therefore, supposed antitumor action. The aim of this study was to evaluate the effects of GA on the formation of aberrant crypts, as well as the local, hepatic, and systemic genotoxicity and oxidative stress. We induced colorectal carcinogenesis in Swiss male mice, afterwards treated them with water, 2.5% GA or 5% GA via gavage for twelve weeks and then performed surgery in order to obtain samples to analysis (proximal and distal colon, liver, blood, and bone marrow). The number of aberrant crypts in the GA-treated animals was lower than in the control groups. Likewise, there was a decline of colonic, hepatic, and systemic genotoxicity and oxidative stress. These results reflect the antioxidant role of GA and may lead to the development of treatments that inhibit colorectal carcinogenesis.

«Kolidev 8M» (powder for oral use) is a veterinary drug used to treat ornamental birds (pheasants, peacocks) in diseases of the digestive tract caused by microorganisms sensitive to colistin. In the study of the drug «Kolidev 8M» for oral administration, along with the confirmation of therapeutic properties, it is necessary to determine the LD50obtained in the process of studying acute toxicity. The aim of research.The aim of research was to determine the acute toxicity of the veterinary drug «Kolidev 8M» (powder for oral administration) under the conditions of intragastric administration to white mice. Materials and methods of research. To achieve this aim, an experiment was conducted on 114 males of nonlinear white mice kept under optimal conditions in the vivarium of DEVIE LLC (Rivne, Ukraine). In the first series of experiments on the principle of analogues was formed control and three experimental groups of 6 animals each (n=6). The drug in the form of a solution was administered once orally using a esophageal gastric tube in doses of 500,0; 2000,0 and 4000,0 mg/kg body weight by absolute weight of the drug. The animals of the control group were injected with distilled water. After taking into account the results of the first experiment in the next experiment, 6 experimental groups were formed – mice, which were administered the drug «Kolidev 8M» in the form of a solution in doses (by absolute weight of the drug) – 500,0; 1000,0; 1500,0; 2000.0; 2500,0; 3000,0; 3500 and 4000,0 mg/kg body weight, as well as the control group – animals that were injected with distilled water with a volume of 0.5 cm3according to similar regulations (Zapadniuk, 1983; Kotsiumbas, 2005; Karkyshchenko & Hrachev, 2010). There were 6 animals in each group (n=6). After their death, a pathological autopsy was performed (Zharov A. et al., 2003). The average lethal dose of LD50was calculated by the method of probit analysis by Prozorovsky V.B. Research results.According to the results of research, it was found that the LD50 of the drug «Kolidev 8M» (powder for oral administration) under the conditions of its single intragastric administration to male mice is 2024,72±232,45 mg/kg, LD10– 392,87 mg/kg, LD16– 751,56 mg/kg, LD84– 3297,88 mg/kg, LD90– 3656,57 mg/kg, LD100– 3934,47 mg/kg body weight, respectively. According to the results of an acute toxicological experiment with intragastric administration of the drug «Kolidev 8M» to white male mice, LD50was 2024,72±232,45 mg/kg body weight. This allows, according to toxicity, to refer this drug to class IV – low-toxic substances (LD50501,0-5000,0 mg/kg body weight), and the degree of danger to class III – moderately safe substances (LD50151,0-5000,0 mg/kg body weight). Conclusions and prospects for further research.The drug «Kolidev 8M» in terms of toxicity belongs to class IV – low-toxic substances, and the degree of danger to class III – moderately safe substances. Further studies will be the next stage of pre-registration trials aimed at studying the subacute toxicity of the drug «Kolidev 8M&raquo

Gentle stroking, a type of affective touch that holds hedonic and rewarding value, is critical to our daily inter-individual communication. This positive socio-emotional aspect of touch is conveyed through a subclass of C afferents known as C-Tactile fibers in humans with an analogous system in rodents proposed. Here, we describe a novel tactile conditioned place preference paradigm using mice and demonstrate that gentle stroking by an experimenter is rewarding. In order to investigate the relationship between tactile preference and innate sociability, mice were subjected to the classic three-chambered test of social approach, where mice displayed significant preference towards the experimenter's hand. These findings suggest that gentle stroking evoked by an experimenter can play an important role in reward and preference and establish an affiliative relationship between mice and humans. Future research can potentially use this model to examine fiber type involvement and elucidate the significance of these findings for activation of the reward system.

While most pup-naïve adult female mice can display, or be induced (by repeated exposure to pups) to display parental behavior rapidly, adult males are infanticidal or nonparental. The medial prefrontal cortex (mPFC) participates in attentional selection, decision-making, behavioral flexibility, and planning that may be critical in the rapid display of parental or infanticidal behavior. We investigated if NMDA-induced lesions in the mPFC (targeting prelimbic cortex) inhibited maternal or infanticidal behavior in pup-naïve adult female and male mice (C57BL/6), respectively. All Control females displayed full maternal behavior at the first encounter with pups. Lesioned female groups were partially maternal (50%) or nonmaternal (50%). Five repeated exposures of 60-min to pups were needed to induce full maternal behavior in female NMDA-lesioned groups. Control and lesioned males did not show significant differences. Control males displayed nonparental (17%) or infanticidal (83%) behavior, while all lesioned males were infanticidal. There was no difference in general locomotor and exploratory activity (i.e., peripheral crosses, rearings, immobility time) in female or male groups. Nevertheless, females and males of lesioned groups showed a reduction in the number of central crosses and time in the central area of an open field respectively, suggesting an increase in anxiety. Our results show that the mPFC is engaged in the rapid onset of maternal behavior in females, contributing with the motivation and planning of its rapid execution, or reducing the anxiety to the first encounter with pups. In contrast, infanticidal behavior, likely a more impulsive behavior, might require less planning from the mPFC. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Memory loss is the key symptom of Alzheimer's disease (AD). As successful drug treatments have not yet been identified, non-pharmaceutical intervention, such as physical exercise has been recognized as an effective strategy to improve memory function of people with dementia. Here we investigated the effect of prolonged physical running on hippocampal-dependent spatial memory and underlying mechanisms in 3xTg-AD mouse, a well-established rodent model of Alzheimer's disease (AD). Methods: 3xTg-AD transgenic mice with three AD mutations were used and compared with non-transgenic mice. Voluntary wheel running continued for 5 months (1 hour per day, 5 days per week) and was followed by spatial memory testing. At the end of behavior testing, dendritic spines, synapses, and synaptic proteins as well as amyloid-beta (Aβ) pathology were analyzed in the dorsal hippocampi. Results: Running improved hippocampal-dependent spatial memory in 3xTg-AD mice. This running strategy prevented both thin and mushroom-type spines on CA1 pyramidal cells in 3xTg-AD mice, whereas the effects of running in non-transgenic mice were limited to thin spines. The enormous effects of running on spines were accompanied by increased synapses and higher expressions of synaptic proteins. Notably, running downregulated the processing of amyloid precursor protein, resulting in reduced Aβ peptides, and spatial memory performance correlated with levels of Aβ peptides Aβ1-40 and Aβ1-42. Conclusion: These data suggest that prolonged running may improve memory in preclinical AD via slowing down amyloid pathology and preventing loss of synaptic contacts.

Quantification of interindividual variability is a continuing challenge in risk assessment, particularly for compounds with complex metabolism and multi-organ toxicity. Toxicokinetic variability for perchloroethylene (perc) was previously characterized across 3 mouse strains and in 1 mouse strain with various degrees of liver steatosis. To further characterize the role of genetic variability in toxicokinetics of perc, we applied Bayesian population physiologically based pharmacokinetic (PBPK) modeling to the data on perc and metabolites in blood/plasma and tissues of male mice from 45 inbred strains from the Collaborative Cross (CC) mouse population. After identifying the most influential PBPK parameters based on global sensitivity analysis, we fit the model with a hierarchical Bayesian population analysis using Markov chain Monte Carlo simulation. We found that the data from 3 commonly used strains were not representative of the full range of variability in perc and metabolite blood/plasma and tissue concentrations across the CC population. Using interstrain variability as a surrogate for human interindividual variability, we calculated dose-dependent, chemical-, and tissue-specific toxicokinetic variability factors (TKVFs) as candidate science-based replacements for the default uncertainty factor for human toxicokinetic variability of 100.5. We found that toxicokinetic variability factors for glutathione conjugation metabolites of perc showed the greatest variability, often exceeding the default, whereas those for oxidative metabolites and perc itself were generally less than the default. Overall, we demonstrate how a combination of a population-based mouse model such as the CC with Bayesian population PBPK modeling can reduce uncertainty in human toxicokinetic variability and increase accuracy and precision in quantitative risk assessment.

The morphological and functional state of the reproductive system was studied in male outbred rats (SD stock) and male F1(CBA×C57BL/6) mice after long-term (3 months) methotrexate administration. The drug was administered subcutaneously once a week for 4 weeks, the dose for male rats was 1 mg/kg, for male mice 2.2 mg/kg. It was found that male rats retained the ability to conceive, their reproductive potential was not limited by increased risk of embryo death. At the same time, signs of astheno- and pathospermia were revealed. The testicular tissue was characterized by reduced content of the sources of the proliferative pool of spermatogenesis. In mice treated with methotrexate, increased content of DNA breaks was detected in the testicular cells.

Background: Apoptosis is the physiological cell death that in natural conditions leads to the elimination of old, damaged, waste, and harmful cells. The aim of this study was the effect of eight weeks of high-intensity interval training (HIIT) with and without caloric restriction on gene expression of myocardial Bax and Bcl2 in mice. Methods: Present study was an experimental multi-group design with a control group conducted on 30 two-month old male mice. Subjects were divided into five homogenous groups including base control, control, caloric restriction, interval exercise training, and caloric restriction + interval exercise training. Training groups participated in interval exercise training five sessions per week for 8 weeks. The level of gene expression of myocardial Bax and Bcl2 was evaluated by real-time PCR. Data were analyzed using the one-way ANOVA at the level of (P

Background Mild traumatic brain injury (mTBI) is common in civilians and highly prevalent among military service members. mTBI can increase health risk behaviors (e.g., sensation seeking, impulsivity) and addiction risk (e.g., for alcohol use disorder (AUD)), but how mTBI and substance use might interact to promote addiction risk remains poorly understood. Likewise, potential differences in single vs. repetitive mTBI in relation to alcohol use/abuse have not been previously examined. Methods Here, we examined how a history of single (1×) or repetitive (3×) blast exposure (blast-mTBI) affects ethanol (EtOH)-induced behavioral and physiological outcomes using an established mouse model of blast-mTBI. To investigate potential translational relevance, we also examined self-report responses to the Alcohol Use Disorders Identification Test-Consumption questions (AUDIT-C), a widely used measure to identify potential hazardous drinking and AUD, and used a novel unsupervised machine learning approach to investigate whether a history of blast-mTBI affected drinking behaviors in Iraq/Afghanistan Veterans. Results Both single and repetitive blast-mTBI in mice increased the sedative properties of EtOH (with no change in tolerance or metabolism), but only repetitive blast potentiated EtOH-induced locomotor stimulation and shifted EtOH intake patterns. Specifically, mice exposed to repetitive blasts showed increased consumption "front-loading" (e.g., a higher rate of consumption during an initial 2-h acute phase of a 24-h alcohol access period and decreased total daily intake) during an intermittent 2-bottle choice condition. Examination of AUDIT-C scores in Iraq/Afghanistan Veterans revealed an optimal 3-cluster solution: "low" (low intake and low frequency), "frequent" (low intake and high frequency), and "risky" (high intake and high frequency), where Veterans with a history of blast-mTBI displayed a shift in cluster assignment from "frequent" to "risky," as compared to Veterans who were deployed to Iraq/Afghanistan but had no lifetime history of TBI. Conclusions Together, these results offer new insight into how blast-mTBI may give increase AUD risk and highlight the increased potential for adverse health risk behaviors following repetitive blast-mTBI.