Sprague-Dawley Rats Research Articles

Anti-implantation and uterotonic properties of Mentha pulegium L. in female Sprague-Dawley rats

Background: Some traditional herbs disrupt endocrine-endometrial synchrony, affecting embryo-endometrium communication during fertility. Hormonal imbalances cause non-receptive conditions, leading to anti-implantation or abortion. Historically, Mentha pulegium has served for contraceptive and abortive purposes. Its effects on the post-coital contraceptive and hormonal activities were evaluated. Methods: Thirty-six Sprague-Dawley female rats were selected based on the presence of copulation plugs and received 200, 500, and 1000 mg/kg of Hydroethanolic leaf extract of Mentha pulegium L. (MPE) for seven days. Reproductive organ weights and serum estrogen and progesterone levels were measured. The resorption index, anti-implantation activity, and pre-implantation loss were also calculated using the number of implantation sites and resorptions in all treatments. Data were presented as mean±standard error mean (SEM), and significance was defined as p<0.05 using one-way ANOVA. Results: Post-coital administration of MPE resulted in resorptive, pre-implantation loss, and anti-implantation activity. A dose of 200 mg/kg reduced the number of implantations and exhibited a high resorption index, percentage pre-implantation loss, and anti-implantation activity. A marked decline in serum progesterone levels and a significant reduction in serum estrogen and progesterone ratio was observed at 200 mg/kg MPE. A significant increase in uterine weight was observed in the 500 mg/kg treatment. Doses of 500 and 1000 mg/kg resulted in a significant reduction in anti-implantation activity. Conclusions: The observed anti-implantation activity and pre-implantation loss suggest the abortifacient properties of MPE. However, its effects were seen to be dose-dependent.

Potential benefit of Lactobacillus acidophilus supplementation to rats fed with a high-fat diet on serum lipid profile, kidney amyloid protein and tumor necrosis factor-alpha level

AimIt was aimed to determine the potential effect of Lactobacillus acidophilus supplementation on rats exposed to an experimental high-fat diet on serum lipid profile and kidney total beta amyloid protein (TBAP) and Tumor Necrosis Factor-alpha (TNF-α) levels. Methods24 male Sprague-Dawley rats were used in the study to establish 4 groups. Standard rat food (SD) was provided to Group 1 as the control; Group 2 was fed a high-fat diet (HFD); Group 3 consumed SD and received L. acidophilus probiotics; Group 4 was fed HFD and received L. acidophilus probiotics. Body weights were determined weekly during the 12-week trial period. At the end of the experiment, TBP and TNF-α levels in the serum and kidney tissue of the rats were measured by ELISA method. Serum total cholesterol (TC), triglyceride (TG), HDL, LDL, urea and creatinine levels and paraoxanase, amylase and lipase activities were determined by spectrophotometric method on the analyzer device. ResultsWhen the control (Group 1) group and Group 2 were compared at the end of the experiment, it was found that Group 2 had gained the most weight and that both the blood and kidney tissue levels of TNF-α and TBAP, as well as the quantities of TG, TK, LDL, and urea, were significantly greater (P<0.05). Serum HDL, PON and amylase levels were found to be significantly low (P>0.05). TG, TK, LDL, urea, and the levels of TNF-α and TBAP in serum and renal tissue were shown to be lower in the groups who received L. acidophilus probiotics (Groups 3, 4) when compared to Group 2 (P>0.05). It was observed that HDL, PON and amylase levels increased and approached the control group (P<0.05). ConclusionThe study's findings showed that probiotic supplementation improved blood levels of TG, TC, HDL, LDL, urea, PON, and amylase as well as serum and kidney tissue levels of TNF-α and TBAP in obese rats fed a high-fat diet.

Supraphysiological Dose of Testosterone Impairs the Expression and Distribution of Sex Steroid Receptors during Endometrial Receptivity Development in Female Sprague-Dawley Rats.

This study aims to investigate the effect of a supraphysiological dose of testosterone on the levels of sex steroid hormones and the expression and distribution of sex steroid receptors in the uterus during the endometrial receptivity development period. In this study, adult female Sprague-Dawley rats (n = 24) were subcutaneously administered 1 mg/kg/day of testosterone alone or in combination with the inhibitors (finasteride or anastrozole or both) from day 1 to day 3 post-coitus, while a group of six untreated rats served as a control group. The rats were sacrificed on the evening of post-coital day 4 of to measure sex steroid hormone levels by ELISA. Meanwhile, gene expression and protein distribution of sex steroid receptors were analysed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC), respectively. In this study, treatment with a supraphysiological dose of testosterone led to a significant reduction in oestrogen and progesterone levels compared to the control. The mRNA expression of the androgen receptor increased significantly in all treatment groups, while the mRNA expression of both the progesterone receptor and the oestrogen receptor-α decreased significantly in all treatment groups. The IHC findings of all sex steroid receptors were coherent with all mRNAs involved. This study shows that a supraphysiological dose of testosterone was able to interrupt the short period of the implantation window. This finding could serve as a basis for understanding the role of testosterone in endometrial receptivity in order to develop further therapeutic approaches targeting androgen-mediated disorders of endometrial receptivity.

Design, synthesis and evaluation of novel LpxC inhibitors containing a hydrazone moiety as Gram-negative antibacterial agents

LpxC inhibitors are new-type antibacterial agents developed in the last twenty years, mainly against Gram-negative bacteria infections. To enable the development of novel LpxC inhibitors with potent antibacterial activities, several series of compounds were designed and synthesized and their antibacterial activities were evaluated against E. coli ATCC25922, P. aeruginosa ATCC27853, P. aeruginosa clinical isolate PAE 22-1, K. pneumoniae ATCC700603, K. pneumoniae clinical isolate KPN+22-1 in vitro. Compound 6i exhibited significant antibacterial activities against above five Gram-negative bacteria except P. aeruginosa ATCC27853. Moreover, compound 6i exhibited moderate liver microsomal stability and a promising pharmacokinetic profile (AUC0-t = 1050 ng h mL−1, oral bioavailability of 13.3 %) in Sprague-Dawley rats, acceptable PPB, low risk of drug-drug interactions and non-cytotoxic activity against hepatic cell. Collectively, compound 6i could be a promising Gram-negative antibacterial agent for further investigation.

Environmental enrichment and sex, but not n-acetylcysteine, alter extended-access amphetamine self-administration and cue-seeking

There are no approved therapeutics for psychostimulant use and recurrence of psychostimulant use. However, in preclinical rodent models environmental enrichment can decrease psychostimulant self-administration of low unit doses and cue-induced amphetamine seeking. We have previously demonstrated that glutamate-dependent therapeutics are able to alter amphetamine seeking to amphetamine-associated cues only in enriched rats. In the current experiment, we will determine if enrichment can attenuate responding and cue-induced amphetamine seeking during extended access to a high dose of intravenous amphetamine. We will also determine if N-acetylcysteine (NAC), a glutamate dependent therapeutic, can attenuate amphetamine seeking in differentially reared rats. Female and male Sprague-Dawley rats were reared in enriched, isolated, or standard conditions from postnatal day 21–51. Rats were trained to self-administer intravenous amphetamine (0.1 mg/kg/infusion) during twelve 6-hour sessions. During the abstinence period, NAC (100 mg/kg) or saline was administered daily. Following a cue-induced amphetamine-seeking test, astrocyte densities within regions of the medial prefrontal cortex (mPFC) and nucleus accumbens (ACb) were quantified using immunohistochemistry. Environmental enrichment decreased responding for amphetamine and during the cue-induced amphetamine-seeking test. NAC did not attenuate cue-induced amphetamine seeking or alter astrocyte density. Across all groups, female rats self-administered less amphetamine but responded more during cue-induced amphetamine seeking than male rats. While amphetamine increased astrocyte densities within the ACb and mPFC, it did not alter mPFC astrocyte densities in female rats. The results suggest that enrichment can attenuate responding during extended access to a high dose of amphetamine and the associated cues. Sex alters amphetamine-induced changes to astrocyte densities in a regionally specific matter.

Anatomical and Micro-CT measurement analysis of ocular volume and intraocular volume in adult Bama Miniature pigs, New Zealand rabbits, and Sprague-Dawley rats

Anatomical and Micro-CT measurement analysis of ocular volume and intraocular volume in adult Bama Miniature pigs, New Zealand rabbits, and Sprague-Dawley rats

E5 treatment showing improved health‐span and lifespan in old Sprague Dawley rats

AbstractAging and, in particular, the emergence of age‐related disorders is associated with tissue dysfunction and macromolecular damage, some of which can be attributable to accumulated oxidative damage. In the current study, we determine the potential of ‘plasma‐derived fraction (E5)’ for cellular rejuvenation and extending the lifespan of Sprague Dawley (SD) rats. This is a unique study wherein we have used 24‐month‐old rats and monitored them until the end of their lifespan with and without E5 treatment. In the present investigation, the SD rats were separated into two groups old control group and the treatment group (n = 8). The treatment group received four injections of E5 every alternate day for 8 days, and eight injections every alternate day for 16 days. Body weight, grip strength, cytokines, and biochemical markers were measured for more than 400 days of the study. Clinical observation, necropsy, and histology were performed. The E5 treatment exhibited great potential by showing significantly improved grip strength, remarkably decreased pro‐inflammatory markers of chronic inflammation and oxidative stress, as well as biomarkers for vital organs (BUN, SGPT, SGOT, and triglycerides), and increased anti‐oxidant levels. Clinical examinations, necropsies, and histopathology revealed that the animals treated with the E5 had normal cellular structure and architecture. In conclusion, this unique ‘plasma‐derived exosome’ treatment (E5) alone is adequate to improve the health‐span and extend the lifespan of the old SD rats significantly.

Identification of daurisoline metabolites in rats via the UHPLC-Q-exactive orbitrap mass spectrometer

Daurisoline, a bisbenzylisoquinoline alkaloid extracted from the rhizomes of Menispermum dauricum, exhibits diverse biological activities, encompassing antiplatelet, anti-inflammatory, neuroprotective, and antitumor properties. However, previous investigations have not comprehensively elucidated the metabolic profile and pathways of daurisoline in vivo. Using Ultra-High-Performance Liquid Chromatography with Q-Exactive Orbitrap Mass Spectrometry technology, we comprehensively investigated the metabolites of daurisoline in Sprague-Dawley rats, following intragastric administration. Data collection and analysis were enhanced through Full Scan MS/dd-MS2, in conjunction with parallel reaction monitoring, extracted ion chromatography, and diagnostic fragment ions. Sixty-three metabolites were detected and characterized, including sixty-two novel metabolites and coclaurine. This investigation elucidated the cleavage patterns and tissue distribution characteristics of the metabolism of daurisoline. Furthermore, in vivo reactions, including dehydrogenation, hydroxylation, methylation, sulfation and glucuronidation, were thoroughly examined. Investigating the metabolites of daurisoline in rats has deepened our understanding of its metabolism in vivo, aiding in elucidating its metabolic and pharmacological actions. This provides a valuable foundation for further research into its therapeutic efficacy.

Research on the Improvement of Endothelial Cell Function and Trophoblast Apoptosis in Rats with Preeclampsia by Tanshinone IIA

Background Preeclampsia is a pregnancy complication characterized by high blood pressure and signs of damage to another organ system, often the kidneys. Recent studies suggest that endothelial dysfunction and trophoblast apoptosis are involved in the pathogenesis of preeclampsia. Purpose To investigate the effects of tanshinone IIA (TIIA) on clinical symptoms, vascular endothelial function, and placental trophoblast apoptosis in preeclampsia rats. Materials and Methods Twenty-four pregnant Sprague-Dawley rats, between 8 and 10 weeks old, were randomly divided and allocated into three groups: Control, model, and treatment, with each group consisting of 8 rats. The control group received normal saline injections via the tail vein; the model group received NG-nitro-l-arginine methyl ester (l-NAME) to induce preeclampsia, followed by normal saline injections; and the treatment group received TIIA (10 mg/kg) via tail vein injection after preeclampsia induction with l-NAME. Various parameters were measured, including tail artery systolic pressure, 24-hour proteinuria, offspring and placental weight, levels of endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), placental growth factor (PLGF), and soluble FMS-like tyrosine kinase 1 (sFlt-1) in serum, and expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2-related X protein (Bax) in placental trophoblasts. Results TIIA treatment led to decreased tail artery systolic pressure and 24-hour urine protein levels, increased body and placental weights of offspring, and favorable changes in serum levels of ET-1, sFlt-1, eNOS, and PLGF. Moreover, TIIA treatment resulted in decreased Bax levels and apoptosis in placental trophoblasts, along with increased Bcl-2 levels. Conclusion TIIA can improve the clinical symptoms of preeclampsia in rats induced by l-NAME, alleviate the apoptosis of placental trophoblast cells, and improve vascular endothelial function.

Optogenetic stimulation of dorsal striatum bidirectionally controls seizures.

Engagement of the striatum (caudate/putamen) and other basal ganglia nuclei during seizures was first observed over 75 years ago. Basal ganglia output nuclei, and the substantia nigra pars reticulata, in particular, have well-established anti-seizure effects across a large array of experimental models. However, striatal control of seizures is understudied. To address this gap, we used optogenetic approaches to activate and inactivate neurons in the dorsal striatum of Sprague-Dawley rats submitted to the gamma-butyrolactone (GBL) model of absence epilepsy, amygdala kindling model of temporal lobe epilepsy, and pilocarpine-induced Status Epilepticus (SE). All tests were performed on a within-subject basis. Animals were tested in two different light frequencies (5 Hz and 100 Hz). Open-loop (continuous light delivery) optogenetic activation of the dorsal striatal neurons robustly suppressed seizures in all models. On the other hand, optogenetic silencing of the dorsal striatal neurons increased absence seizure expression and facilitated SE onset but had no effect on kindled limbic seizures. In the GBL model, we also verified if the closed- loop strategy (light delivery in response to seizure detection) would be enough to induce antiseizure effects. On-demand light delivery in ChR2-expressing animals reduced SWD duration, while the same approach in ArchT-expressing animals increased SWD duration. These results demonstrated previously unrecognized anti-absence effects associated with striatal continuous and on-demand neuromodulation. Together, these findings document a robust, bidirectional role of the dorsal striatum in the control of seizure generation and propagation in a variety of seizure models, including focal seizure onset and generalized seizures.

Assessment of Antioxidant and Hepatoprotective Effects of Kappaphycus alvarezii (Doty) Doty ex Silva Against Carbon Tetrachloride-Induced Liver Injury in Rats

Kappaphycus alvarezii (Doty) Doty ex Silva, commonly known as red algae, holds economic significance as a primary source of κ-carrageenan, which exhibits promising medicinal and therapeutic properties. This study aims to assess the antioxidant potential as well as hepatoprotective activity of the ethanolic extract of K. alvarezii (EEKA). The assays utilised to determine the antioxidant properties of EEKA were total phenolic content (TPC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging. In addition, the ability of EEKA to ameliorate experimentally induced liver injury in Sprague-Dawley rats caused by carbon tetrachloride (CCl4) was evaluated. The biochemical assays involved measuring liver marker enzymes (AST and ALT) in serum as well as determining the levels of reduced glutathione (GSH), lipid peroxidation (LPO) via malondialdehyde, catalase (CAT), and glutathione S-transferase (GST) in liver homogenates. The TPC and DPPH radical scavenging activity of EEKA demonstrated relatively low antioxidant properties compared to standard references. However, CCl4-induced groups exhibited significantly increased levels of AST and ALT, along with depletion of antioxidant status (GSH, CAT, and GST) indicated by LPO. Pretreatment with EEKA resulted in slightly decreased liver marker enzyme activity and LPO, coupled with an increase in antioxidant status. These findings suggest that EEKA contains active principles capable of counteracting the hepatotoxic effects induced by CCl4.

Protective effect of propolis in protecting against radiation-induced oxidative stress in the liver as a distant organ

Stresses caused by ionizing radiation can also damage tissues and organs through the circulatory system. In this study, we aimed to determine the radioprotective effect of propolis, a natural and powerful antioxidant product, against oxidative liver damage caused by cranial irradiation. Thirty-two male albino Sprague–Dawley rats, divided into four groups, were designed as sham group, irradiation (IR) group, propolis plus IR, control group of propolis. Biochemical parameters were measured in liver tissue of rats. While Total enzymatic superoxide scavenging activity (TSSA) and non-enzymatic superoxide scavenging activity (NSSA), glutathione peroxidase (GSH-Px) activities of all groups were statistically significantly higher than rats receiving only-irradiation, Glutathione-S-transferase (GST) activity in the IR group was significantly lower than in the sham control group and IR + propolis group. Superoxide dismutase (SOD) activity in the IR group was found to be significantly higher than both the sham control group and the propolis control group, but lower than the IR + propolis group. Malondialdehyde level and xanthine oxidase activity were higher in the IR group than in the other groups. Compared to the sham control group, in the group treated with propolis, a significant elevation in antioxidant parameters, specifically TSSA, NSSA, SOD, and GST activities, was noted, with corresponding increases of 32.3%, 23.2%, 47.6%, and 22.6%, respectively. Our findings show that propolis can be a radioprotective agent against ionized radiation damage by increasing antioxidant activity and reducing oxidant stress in liver tissue.

Short-term Uridine Treatment Alleviates Endoplasmic Reticulum Stress via Regulating Inflammation and Oxidative Stress in Lithium-Pilocarpine Model of Status Epilepticus

Background: Status Epilepticus (SE) leads to the development of epilepsy with the contribution of Endoplasmic Reticulum (ER) stress. Uridine, a pyrimidine nucleoside, has been shown to have neuroprotective and antiepileptogenic effects in animal models. This study aimed to determine whether uridine ameliorates ER stress and apoptosis following epileptogenic insult. Secondly, this study aimed to establish the effect of uridine on inflammatory and oxidative stress parameters that contribute to ER stress. Methods: Status epilepticus was induced using lithium-pilocarpine in adult male Sprague-Dawley rats. Following SE termination, rats were treated with uridine, 4-phenylbutyric acid (4-PBA), or saline twice daily for 48 h. Expressions of hippocampal glucose-regulated protein 78 (GRP78), Inositol- Requiring Protein 1 (IRE1α), Protein kinase RNA-like Endoplasmic Reticulum Kinase (PERK), and C/EBP Homologous Protein (CHOP) were determined by western blotting 48 h after SE. Uridine's effects on apoptosis, inflammation or oxidation were evaluated by analyses of cleaved caspase-3 and poly(ADP-ribose) polymerase 1 (PARP1) protein expressions or pro-inflammatory cytokine levels or levels of oxidative stress markers, respectively. Results: Expressions of all ER stress-related proteins significantly increased 48 h after SE. Uridine treatment markedly decreased GRP78, IRE1α, and CHOP levels. A decrease in the PERK level was observed following the administration of 4-PBA; however, uridine had no effect. Cleaved caspase-3 and PARP1 levels were increased in the SHAM group, while uridine and 4-PBA treatment effectively decreased their expressions. Treatment with uridine significantly reduced Myeloperoxidase (MPO) and Malondialdehyde (MDA) levels while tending to increase Catalase (CAT) and Glutathione Peroxidase (GPx) levels. Uridine treatment also significantly attenuated levels of TNF-α and IL-1β, the pro-inflammatory cytokines, which increased 48 h post-SE. Conclusion: Our data indicate that uridine alleviates ER stress after SE. This effect may be attributed to the regulation of inflammation and oxidative stress. Uridine shows promise as a potential preventive agent for epilepsy.

Development of a chronic compression spinal cord injury model in neonatal and adult rats.

Spinal cord injury presents a significant burden globally, with traumatic spinal cord injury being the predominant cause historically. However, nontraumatic spinal cord injury (NTSCI) is emerging as a significant contributor, particularly in developed nations, yet it remains poorly understood due to underreporting and misclassification. NTSCI, spanning various etiologies such as bony growths, vascular conditions, infections, neoplastic conditions, and immune disorders, poses unique challenges in diagnosis and treatment, often resulting in lifelong morbidity. This study addresses the lack of suitable animal models for NTSCI research, especially in neonatal animals. Utilizing a solid spacer approach, we developed a compression NTSCI model applicable to both neonatal and adult Sprague-Dawley rats. Through anatomical measurements and invivo experiments, we confirmed the feasibility and safety of the spacer insertion procedure and observed no acute off-target effects. The versatility of this model lies in its adaptability to different ages of rats, offering a cost-effective and reproducible means to induce graded injuries. Moreover, behavioral assessments demonstrated observable hindlimb function, validating the model's utility for studying functional outcomes. Although challenges persist, particularly in accounting for spinal column growth in neonatal animals, this model fills a crucial gap in pediatric NTSCI research. By providing a platform to investigate pathophysiological mechanisms and test potential treatments, it offers promising avenues for advancing our understanding and management of pediatric NTSCI.

Resveratrol Protects Müller Cells Against Ferroptosis in the Early Stage of Diabetic Retinopathy by Regulating the Nrf2/GPx4/PTGS2 Pathway.

The aim of this study was to investigate the anti-ferroptotic effect of resveratrol (RSV) on retinal Müller cells (RMCs) in the early stages of diabetic retinopathy (DR) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPx4)/prostaglandin-endoperoxide synthase 2 (PTGS2). The retina was obtained from normal and diabetic Sprague-Dawley rats or wild-type and Nrf2 knockout (KO) diabetic mice, with or without RSV (10mg/kg/d) treatment for 12weeks. RMCs transfected with or without SiNrf2 were cultured with high glucose and RSV (20mM). The retinal neurofunctional changes were measured by electroretinogram (ERG). The retinal inner nuclear layer cell mitochondrial morphological changes were detected by transmission electron microscopy. The cell viabilities were measured by cell counting kit-8 (CCK-8) assay. The levels of Fe2+, malonic dialdehyde (MDA), and glutathione (GSH) were measured by colorimetric method. The expression of Nrf2, GPx4, and PTGS2 was detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunocytochemistry. In vivo, RSV inhibited retinal neurofunctional changes and mitochondrial morphological changes; decreased Fe2+, MDA, and PTGS2; and increased GSH, Nrf2, and GPx4 in retina of DM rats. In vitro, RSV decreased MDA and PTGS2 and increased cell viability, GSH, Nrf2, and GPx4. In vivo and vitro, the role of Nrf2-regulated signaling pathway in anti-ferroptosis by RSV was further confirmed using Nrf2 KO mice and pre-transfected SiNrf2 in RMCs. These findings indicated that RSV is a potential therapeutic option for DR and that Nrf2/GPx4/PTGS2 plays a role in the anti-ferroptosis mechanism of RSV on RMCs.

Preventive effects of transcutaneous CO2 application on disuse osteoporosis and muscle atrophy in a rat hindlimb suspension model

We previously demonstrated that transcutaneous CO2 application promotes muscle fiber-type switching, fracture healing, and osteogenesis by increasing blood flow and angiogenesis. Here, we aimed to investigate the preventive effects of transcutaneous CO2 application on disuse osteoporosis and muscle atrophy in a rat hindlimb suspension model. Eleven-week-old male Sprague-Dawley rats were divided into hindlimb suspension (HS), HS with transcutaneous CO2 application (HSCO2), and control groups. HSCO2 rats were administered transcutaneous 100 % CO2 gas in their bilateral hindlimbs, five times a week for 20 min. After 3 weeks, we harvested the gastrocnemius, femur, and tibia for assessment. Histological analysis revealed a significant decrease in the gastrocnemius myofiber cross-sectional area in HS rats compared to the control rats, whereas HSCO2 rats exhibited a significant increase compared to HS rats. Micro-computed tomography showed significant bone atrophy in the trabecular and cortical bones of the femur in HS rats compared to those of the control rats, whereas significant improvement was noted in HSCO2 rats. Histological analysis of the proximal tibia revealed more marrow adipose tissue in the HS rats than in the control rats. However, in the HSCO2 rats, fewer marrow adipose tissue and osteoclasts were observed. Moreover, HSCO2 rats had more osteoblasts and higher expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and vascular endothelial growth factor (VEGF) than the HS rats. The gastrocnemius and distal femur of HSCO2 rats also exhibited elevated PGC-1α and VEGF expression and upregulation of the myogenesis markers and osteogenesis markers compared to those of HS rats. This treatment effectively prevented disuse osteoporosis and muscle atrophy by promoting local angiogenesis and blood flow. PGC-1α is crucial for promoting this angiogenic pathway. Transcutaneous CO2 application may be a novel preventive procedure for disuse osteoporosis and muscle atrophy, complementing medication and rehabilitation.

Neurobehavioral assessment of BMEDA by modified Irwin test in Sprague-Dawley rats

The neurobehavioral assessment of N,N-bis(2-mercapatoethly)-N′,N′-diethylenediamine (BMEDA), which can form a chelate with rhenium-188 (188Re) to produce the 188Re-BMEDA-liposome, was evaluated. The purpose of this study was to evaluate the potential neurobehavioral changes by using the functional observational battery observation procedures when intravenous injection of BMEDA to Sprague-Dawley rats. Rats were administered BMEDA at dose levels of 1, 2, and 5 mg/kg. No mortalities were observed. There are some observations related to BMEDA treatment found in the 5 mg/kg dose group at 10 min post-dose. Tremor was observed in one male rat and seven female rats. The increased respiration, vocalization, not easy to handle and/or loss of tone in the limb were observed in both males and females, and increased body temperature was observed in male animals. Based on the results, a single intravenous dose of BMEDA administered to rats resulted in increased respiration, vocalization, not easy to handle and/or loss of tone in the limb increasing at the dose level of 5 mg/kg. No neurobehavioral effects were noted after BMEDA administration up to the dose level of 2 mg/kg. The information of this study will provides a point of reference to design appropriately therapeutic studies for future human use.

The anxiogenic drug yohimbine is a reinforcer in male and female rats.

The indole alkaloid yohimbine is an anxiogenic drug that activates stress-responsive systems in the brain. However, because yohimbine also elicits approach behaviors, this study employed male and female Sprague-Dawley rats to explore its potential reinforcing effects. Thus, it was first determined if intravenous (IV) infusions of yohimbine (0.25 mg/kg/infusion) could maintain lever pressing, whether intake could be modulated by dose/infusion, and if lever pressing would persist in the absence of yohimbine or yohimbine-paired cues. Next, to assess yohimbine's effect on memory consolidation, 0.3, 1.25 or 3 mg/kg yohimbine was administered post-training using an object recognition memory task. Finally, place conditioning assessed whether doses of yohimbine that elevate blood serum corticosterone levels (1.25 or 3 mg/kg) couldelicit a conditioned place preference. It was found that both sexes acquired yohimbine IV self-administration, that intake was modulated by dose/infusion, and that lever pressing persisted during extinction and in the absence of the yohimbine-paired cue. As well, post-training injections of 1.25 mg/kg yohimbine enhanced consolidation of object memory, and 1.25 and 3 mg/kg elevated corticosterone levels and elicited a place preference in both sexes. Finally, in behavioral tests of psychomotor functions, acute yohimbine increased lever pressing for a visual cue and elevated locomotor activity. These findings reveal a profile of yohimbine's behavioral effects that is consistent with that of psychostimulant reinforcing drugs.

Effect of Purified Resveratrol Butyrate Ester Monomers against Hypertension after Maternal High-Fructose Intake in Adult Offspring.

Offspring hypertension arising from adverse maternal conditions can be mitigated through dietary nutritional supplementation, including resveratrol. Previously, we identified derivatives of resveratrol butyrate ester (RBE), specifically 3,4'-di-O-butanoylresveratrol (ED2) and 3-O-butanoylresveratrol (ED4), demonstrating their superior antioxidant capabilities compared to RBE itself. This study sought to assess the protective impact of maternal supplementation with ED2 or ED4 on offspring hypertension in a rat model subjected to a high-fructose (HF) diet during pregnancy and lactation. Female Sprague-Dawley rats were distributed into distinct dietary groups throughout pregnancy and lactation: (1) standard chow; (2) HF diet (60%); (3) HF diet supplemented with ED2 (25 mg/L); and (4) HF diet supplemented with ED4 (25 mg/L). Male offspring were euthanized at the age of 12 weeks. The maternal HF diet induced hypertension in the offspring, which was mitigated by perinatal supplementation with either ED2 or ED4. These protective effects were attributed to the antioxidant properties of ED2 and ED4, resulting in an increased availability of nitric oxide (NO). Additionally, supplementation with ED2 was connected to an increased abundance of Bifidobacterium and Clostridium genera, which was accompanied by a decrease in Angelakisella and Christensenella. On the other hand, ED4 supplementation shielded rat offspring from hypertension by elevating concentrations of short-chain fatty acids (SCFAs) and their receptors while reducing trimethylamine-N-oxide (TMAO) levels. These findings highlight the potential of purified RBE monomers, ED2 and ED4, as preventive measures against hypertension resulting from a maternal high-fructose diet. Further research is warranted to explore their clinical applications based on these promising results.

Study on the mechanism of Shenling Baizhu powder on the pathogenesis of pregnancy complicated with non-alcoholic fatty liver, based on PI3K/AKT/mTOR signal pathway.

This study investigates the effectiveness of Shenlin Baizhu powder in managing non-alcoholic fatty liver disease (NAFLD) during pregnancy and its mechanism through the PI3K/AKT/mTOR signaling pathway. Eight healthy male and 24 female Sprague-Dawley rats were used. After acclimatization, 6 female rats were fed normal chow, and 18 female rats were fed high-fat chow to induce NAFLD. After 8 weeks, female rats were mated with males to create a pregnant NAFLD model. The rats were divided into four groups: normal feeding, high-fat diet with saline, high-fat diet with 1.6 g/kg Shenlin Baizhu powder, and high-fat diet with 4.8 g/kg Shenlin Baizhu powder. Maternal body weight, serum and liver levels of aspartate aminotransferase (AST), alanine transaminase (ALT), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), related inflammatory indexes interleukin-1 β (IL-1 β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured. Liver tissue was examined using hematoxylin and oil red O staining, and protein expression related to the PI3K/AKT/mTOR pathway was assessed via Western blotting, immunohistochemistry and RT-PCR. Results showed significant weight gain and increases in ALT, AST, TG, TC, LDL-C, IL-1β, TNF-α, and IL-6, along with decreased HDL-C in NAFLD rats compared to controls. The high and low-dose Shenlin Baizhu powder groups exhibited improvements in body weight, liver histopathology, and reductions in serum TG, TC, LDL-C, ALT, AST, IL-1β, TNF-α, and IL-6, with increased HDL-C levels. Notably, the high-dose group showed greater efficacy in reducing hepatic fat accumulation, liver function markers, blood lipids, and inflammatory indexes, and decreased expression of hepatic PPARγ mRNA, SREBP1 mRNA, AKT mRNA, and related proteins. Shenlin Baizhu powder demonstrates potential in ameliorating high-fat diet-induced NAFLD in pregnant rats, likely through modulation of the PI3K/AKT/mTOR pathway, suggesting its therapeutic potential for gestational NAFLD.