Body Weight Of Rats Research Articles

Assessment of Morphological Changes in the Oral Mucosa of Laboratory Rats when Exposed to Salt

According to a report by the World Health Organization on July 31, 2023, the tobacco epidemic remains one of the main threats to the health of the world’s population, more than 7 million people die from tobacco exposure and 1.3 million deaths are caused by exposure to second-hand tobacco smoke. In Central Asia, the most popular form of smokeless tobacco use is nasvai. To study histological changes in the oral mucosa in laboratory rats when exposed to salt. 40 male laboratory rats weighing 170-240 g were selected for the study. The animals involved in the experiment were divided into two groups: experimental and intact, with twenty individuals in each. The restoration of the methodology in the experimental group included protective placement of tobacco, the dose of tobacco products was determined depending on the body weight of laboratory rats. The rodents were fed with ordinary feed pellets and kept in ventilated cages with controlled humidity and temperature. Nasvai was placed in the oral cavity between the cheek and gum once a day two hours before meals. According to the European Convention for the Protection of Vertebrates ETSN no. 123, after a 30-day experiment, laboratory animals were removed from the experiment by overdosing on general anesthesia. Oral tissue samples were extracted and fixed in a 10% formalin solution with further routine degreasing and dehydration methods. During the further stage of the experiment, sections with a thickness of 7 microns were prepared and hematoxylin-eosin staining was used to identify the characteristics of the tissues of the oral cavity by microscopy. When studying the histological structure of the oral mucosa of laboratory rats, as a result of exposure to nasvai, obvious signs of the immuno-inflammatory process and hyperkeratosis were revealed.

Shramahara Mahakasya, a traditional polyherbal formulation, induces anti-anxiety activity in hippocampal neurons by effectuating SOD2-mediated protection against oxidative stress

BackgroundShramahara Mahakasya (SM) is an Ayurvedic polyherbal formulation known for its anti-fatigue and anti-anxiety effects on the human body. However, its mechanism of action remains largely unexplored. In this study, we investigated the intricate mechanisms through which SM polyherbal extract exerts the neuroprotective and anxiolytic effects in cultured HT-22 cells and rodent models. MethodIn this study, the chemical composition of SM was first identified using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The antioxidant potential of SM was evaluated through antioxidant assays such as DPPH, ABTS and FRAP. The neuroprotective activity of SM (200 and 600 μg/mL) was investigated in glutamate (10 mM) assaulted HT-22 cells. The anxiolytic activity of SM (50 and 100 mg/kg) was assessed in a caffeine (50 mg/kg) induced anxiety model of Sprague Dawley rats. The possible underlying mechanisms for the neuroprotective and anxiolytic activities of SM were explored through biochemical assays and brain histology. ResultsOur findings suggest that SM has antioxidant and neuroprotective potential, as evidenced by a decrease in ROS accumulation, Ca2+ overload, mitochondrial membrane potential (MMP) loss, and apoptosis in HT-22 cells subjected to glutamate-induced oxidative stress. The extract also increased SOD2 levels and decreased cleaved caspase-3 levels across various treatment sets. The anxiolytic activity of SM was demonstrated by improved behavior of the animals in the elevated plus maze test and increased SOD activity in the brain. SM exhibited the most effective improvements in anxiety disorder at a dose of 100 mg/kg body weight in rats. ConclusionsThis study is a pioneering investigation depicting the antioxidant, neuroprotective, anti-apoptotic, and anxiolytic potential of SM formulation against glutamate/caffeine-induced oxidative stress and anxiety in both in vitro and in vivo situations. Overall, our study suggests that the regular consumption of SM formulation could effectively prevent anxiety symptoms by reducing oxidative stress in neuronal cells.

Intrauterine growth-restricted pregnant rats, from placental ischemic dams, display preeclamptic-like symptoms: A new rat model of preeclampsia.

Preeclampsia (PE) is characterized by de novo hypertension (HTN) and is often associated with intrauterine growth restriction (IUGR). Hallmarks of PE are placental ischemia, decreased nitric oxide (NO) bioavailability, oxidative stress (OS), and organ damage in the kidneys and brain. This study aims to characterize a new model of PE using pregnant IUGR rats from hypertensive placental ischemic dams. It is hypothesized that pregnant IUGR rats from hypertensive placental ischemic dams will have elevated blood pressure (BP), OS, and organ damage. In this study, pregnant rats are divided into two groups: normal pregnant (NP) and hypertensive placental ischemic dams (RUPP). Offspring from NP and RUPP dams were mated at 10 weeks of age to generate pregnant IUGR (IUGR Preg) and pregnant control (CON Preg) rats. BP and other markers of PE were evaluated during late gestation. Pregnant IUGR rats had elevated BP and systemic OS. The maternal body weight of pregnant IUGR rats and their pups' weights were decreased, while the brains were enlarged with elevated OS. In summary, pregnant IUGR rats, born from hypertensive placental ischemic dams, have HTN and increased systemic and brain OS, with larger brain sizes and smaller pups. Furthermore, this study shows that pregnant IUGR rats exhibit a preeclamptic-like phenotype, suggesting a new epigenetic model of PE.

Protective effects of Sphaeranthus indicus floral extract against BPS-induced testicular damage in rats occurs through downregulation of RIPK1/3-MLK-driven necroptosis and Fas-FasL-mediated apoptosis

AbstractBisphenol S (BPS) is one of the monomers preferred in the manufacturing of polycarbonate plastics. Unfortunately, its estrogenic and genotoxic effects are similar to those of bisphenol A. The protective effects of Sphaeranthus indicus floral extract (SFE) against reprotoxic effects of BPS (50 µg/kg per body weight) in rats exposed to it via drinking water was investigated. Different SFE doses (25, 50, and 100 mg/kg) were administered via oral gavage for 10 weeks. High-performance liquid chromatography (HPLC) results indicated that SFE was rich in polyphenols, with rutin and quercetin being important bioactive molecules modulating BPS-induced necroptosis and apoptosis. Biochemical analyses unveiled that rats administered BPS only exhibited considerable elevation of biomarkers of nitro-oxidative stress, necroptotic (RIPK1/RIPK3 and MLKL), and apoptotic mediators (Fas/FasL and caspase 3/caspase-8). These events caused changes in sperm characteristics (sperm motility, sperm head, and sperm viability), sperm count, and hormonal profile (thyroid stimulating hormone, luteinizing hormone, and follicle-stimulating hormone) of the rats. Histological analysis suggested that there was pronounced sloughing of Sertoli cells, reduced spermatogenic cell density, increased levels of seminiferous tubules, and disorganized morphometric parameters related to seminiferous tubules. The SFE supplementation in rats with BPS-containing water restored nitro-oxidative stress biomarkers, which led to the reduction of necroptosis and apoptosis. Reinstatement of all the biomarkers of oxidative stress, inflammation, necroptosis, and apoptosis after SFE supplementations restored the hormonal profile and normal histoarchitecture of the testes. Virtual screening elucidated that the key regulators of the necroptosis are RIPK3-rutin and RIPK1-quercetin complexes. Further studies are needed to assess its pharmacodynamics, kinetics, and effective concentration for daily use in humans.

Wheat bran oil ameliorates high-fat diet-induced obesity in rats with alterations in gut microbiota and liver metabolite profile

BackgroundObesity is one of the public health issues that seriously threatens human health. This study aimed to investigate the effects of wheat bran oil (WBO) on body weight and fat/lipid accumulation in high-fat diet (HFD)-induced obese rats and further explore the possible mechanisms by microbiome and metabolome analyses.MethodsFifty Sprague-Dawley (SD) rats were fed either a normal chow diet (B group, n = 10) or HFD (n = 40) for 14 weeks to establish an obesity model. The HFD-induced obese rats were further divided into four groups and given WBO at 0 mL/kg (M group), 1.25 mL/kg (WBO-L group), 2.5 mL/kg (WBO-M group), and 5 mL/kg (WBO-H group) by oral gavage for 9 weeks. The body weight of rats was weighed weekly. The gut microbiota structure was analyzed using 16 S rDNA high-throughput sequencing. The liver metabolite profile was determined using UHPLC-QE-MS non-target metabolomics technology.ResultsIn this study, WBO treatment reduced body weight gain, fat and lipid accumulation, and ameliorated hepatic steatosis and inflammation. WBO treatment increased the relative abundance of Romboutsia and Allobaculum and decreased that of Candidatus_Saccharimonas, Alloprevotella, Rikenellaceae_RC9_gut_group, Alistipes, Parabacteroides, UCG-005, Helicobacter, Colidextribacter, and Parasutterella compared with the M group. A total of 22 liver metabolites were significantly altered by WBO treatment, which were mainly involved in taurine and hypotaurine metabolism, nicotinate and nicotunamide metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and ether lipid metabolism.ConclusionsWBO alleviated body weight gain and fat/lipid accumulation in HFD-induced obese rats, which may be related to altered gut microbiota and liver metabolites.

Immune Effect of Co-Culture of Dendritic Cells and Cytokine-Induced Killer Cells on Prostate Cancer Cells.

It was to explore the immune outcome of co-culture of dendritic cells (DC) and cytokine-induced killer cells (CIK) on prostate cancer (PCa) cells. Peripheral blood mononuclear cells (PBMCs) were extracted from healthy blood donors. DC and CIK cells were induced and co-cultured. The proliferation and phenotypic changes of DC, CIK, and DC-CIK cells/groups were observed. Model rats were constructed by injecting PC3 PCa cells into the abdominal cavity. The successful 50 cases were divided into a negative control group, a chemotherapy group, a DC group, a CIK group, and a DC-CIK treatment group (each consisting of 10 rats) to observe tumor progression. The secreted concentrations of interleukin-12 (IL-12) ((103.67 ± 2.77) pg/mL) and interferon-γ (IFN-γ) ((730.09 ± 23.52) pg/mL) were higher in DC-CIK group as against DC and CIK groups; the proliferation of CIK was higher in DC-CIK group as against CIK within 12 to 20 days of culture. The positive rate (PR) of CD3+/ CD56+ and CD8+ was higher and that of CD45RA+ was lower in DC-CIK group as against CIK.The killing rate of the DC-CIK group was higher than that of the DC and CIK groups at a target effect ratio of 10:1/20:1/50:1 (P < 0.05). After the treatment, the body weight of rats in the chemotherapy group, DC group, and CIK group was significantly reduced (P < 0.05), while no significant changes were observed in the negative control group and DC-CIK group (P > 0.05). After 25 days of treatment, the tumor size in the DC-CIK group was significantly smaller compared to the negative control group, chemotherapy group, DC group, and CIK group; the necrotic area of the tumor tissue in the DC-CIK group was also significantly larger than that in the negative control group, chemotherapy group, DC group, and CIK group (P < 0.05). Co-culture of DC and CIK is excellent in enhancing the proliferation of CIK cells, increasing the secretion of IL-12 and IFN-γ, and enhancing the activity of immune cells and anti-tumor ability, showing its potential in anti-PCa tumor immunotherapy.

A preliminary study on the effects of Xiang Shao granules on reproductive endocrinology in drugged ovariectomised rats

ObjectiveTo establish a rat model of pharmacological ovariectomy by GnRH-a injection and to preliminarily investigate the reproductive endocrine effects of Xiangshao granules on pharmacologically ovariectomized rats. Methods: A rat model of pharmacological ovariectomy was established by injecting female rats with Gonadotropin-releasing hormone agonist(GnRH-a).The rats were randomly divided into four groups: GnRH-a injected saline group (GnRH-a + NS); GnRH-a injected oestradiol group (GnRH-a + E2); GnRH-a injected Xiangshao granule group (GnRH-a + Xiangshao), and the control group of saline-injected rats (NS + NS). The number of rats per group was 6.According to observations of the rats' vaginal smears, modelling was determined as successful. Then corresponding drug gavage intervention was administered for 28 days, and rat body weight and anal temperature were measured every other day to adjust the drug intervention amount according to body weight changes. Plasma sex hormone levels (E2, FSH, LH), uterine weight, uterine index and endometrial histomorphological changes, ovarian weight, and ovarian index and ovarian histomorphological changes were measured in each group after the gavage.Results(1) Plasma sex hormone levels (E2, FSH, LH) of the GnRH-a + NS, GnRH-a + E2, and GnRH-a + Xiangshao granule groups were significantly lower than the NS + NS group (P < 0.001), while the E2 level of the GnRH-a + E2 group was higher than that of the GnRH-a + Xiangshao granule group (P < 0.05). The FSH level of the GnRH-a + E2 group was significantly lower than that of the GnRH-a + Xiangshao granule group (P < 0.05). The LH level of the GnRH-a + E2 group was significantly lower than those in the GnRH-a + NS and GnRH-a + Xiangshao granule groups (P < 0.001, P = 0.001). The LH and FSH levels of the GnRH-a + NS and GnRH-a + Xiangshao granule groups were not significantly different (P > 0.05). (2) Compared with the NS + NS group, the uterine weight and uterine index, and ovarian weight and ovarian index of GnRH-a injected rats in each model all significantly decreased (P < 0.001). Between the groups, the uterine weight and uterine index, and ovarian weight and ovarian index of GnRH-a + E2 and GnRH-a + Xiangshao granule groups were all significantly higher than those of the GnRH-a + NS group (P < 0.001, P < 0.05). The uterine weight and uterine index, and ovarian weight and ovarian index of the GnRH-a + E2 group increased compared with the GnRH-a + Xiangshao granule group (P < 0.05). (3) Compared with the NS + NS group, the number of primordial follicles of the GnRH-a + NS, GnRH-a + E2, and GnRH-a + Xiangshao granule groups increased significantly and the number of growing follicles and mature follicles significantly decreased. (4) Rats' uterine wall of the NS + NS and various GnRH-a groups was significantly thinner, with the endothelial layer atrophied, while the uterine wall of the GnRH-a + E2 and GnRH-a + Xiangshao granule groups was thicker obviously, with the number of vaginal folds and blood vessels also increasing. Specifically, the uterus and vagina improvements in the GnRH-a + E2 group were more obvious than in GnRH-a + NS and GnRH-a + Xiangshao granule groups.ConclusionGnRH-a injection can reduce the levels of sex hormones E2, FSH, and LH in rats, causing perimenopausal symptoms such as hot flashes, while Xiangshao and E2 granules could significantly improve such symptoms and exert a slight oestrogenic effect, to a lesser extent than E2 does.Trial registrationNot applicable.

Sympathetic Innervation of Interscapular Brown Adipose Tissue Is Not a Predominant Mediator of Oxytocin-Induced Brown Adipose Tissue Thermogenesis in Female High Fat Diet-Fed Rats.

Recent studies have indicated that hindbrain [fourth ventricle (4V)] administration of the neurohypophyseal hormone, oxytocin (OT), reduces body weight, energy intake and stimulates interscapular brown adipose tissue temperature (TIBAT) in male diet-induced obese (DIO) rats. What remains unclear is whether chronic hindbrain (4V) OT can impact body weight in female high fat diet-fed (HFD) rodents and whether this involves activation of brown adipose tissue (BAT). We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of interscapular brown adipose tissue (IBAT) contributes to its ability to activate BAT and reduce body weight in female high HFD-fed rats. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on OT-elicited stimulation of TIBAT and reduction of body weight in DIO rats. We first measured the impact of bilateral surgical SNS denervation to IBAT on the ability of acute 4V OT (0.5, 1, and 5 µg ≈ 0.5, 0.99, and 4.96 nmol) to stimulate TIBAT in female HFD-fed rats. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) stimulated TIBAT similarly between sham rats and denervated rats (p = NS). We subsequently measured the effect of bilateral surgical denervation of IBAT on the effect of chronic 4V OT (16 nmol/day ≈ 16.1 μg/day) or vehicle infusion to reduce body weight, adiposity and energy intake in female HFD-fed rats (N = 7-8/group). Chronic 4V OT reduced body weight gain (sham: -18.0 ± 4.9 g; denervation: -15.9 ± 3.7 g) and adiposity (sham: -13.9 ± 3.7 g; denervation: -13.6 ± 2.4 g) relative to vehicle treatment (p < 0.05) and these effects were similar between groups (p = NS). These effects were attributed, in part, to reduced energy intake evident during weeks 2 (p < 0.05) and 3 (p < 0.05). To test whether these results translate to other female rodent species, we also examined the effect of chronic 4V infusion of OT on body weight and adiposity in two strains of female HFD-fed mice. Similar to what we found in the HFD-fed rat model, we also found that chronic 4V OT (16 nmol/day) infusion resulted in reduced body weight gain, adiposity and energy intake in female DIO C57BL/6J and DBA/2J mice (p < 0.05 vs. vehicle). Together, these findings suggest that (1) sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and weight loss in female HFD-fed rats and (2) the effects of OT to reduce weight gain and adiposity translate to other female mouse models of diet-induced obesity (DIO).

Experimental study of acute toxicity of the intramuscular form of a specific immunobiostimulator — transfer factor

Relevance. The article presents data on the toxicological assessment of the safety of the specific immunobiostimulant of antigen-directed action “Transfer Factor” in a form ready for intramuscular administration and obtained from the blood of hyperimmunized donors on laboratory animals in an acute experiment.Methods. The object of the study was the finished form of “Transfer Factor”, the acute toxicity of which was determined in models on laboratory animals (nonlinear mice, nonlinear rats).Results. It was found that after administration of the drug to mice intramuscularly (0.25 ml/head) and intraperitoneally (0.5 ml/head), to rats intramuscularly (2.5 ml/head) and intraperitoneally (2.5 ml/head), muscle tremor is observed, disappearing after 15–20 minutes. Intraperitoneal administration of the drug to mice and rats in dosages of 0.75 ml/head and 3.75 ml/head, respectively, determines the presence of tremor lasting 40 minutes. During the 14-day observation period, the body weight of mice and rats increases by 10.15-14.25 and 11.84-17.67%. Autopsy of animals does not reveal visible changes in the location of organs and fluid in the abdominal and pleural cavities. However, some pathological changes in color, consistency and size are found in the lungs, heart, spleen and liver with intramuscular administration of Transfer Factor to mice and rats at a dose of 0.25 ml/head and 2.5 ml/head, intraperitoneal administration to mice at a dose of 0.5 ml/head and 0.75 ml/head and to rats 2.5 ml/head and 3.75 ml/head. Based on the totality of changes in the vital signs of laboratory animals, body weight and macroscopic characteristics of internal organs according to GOST 12.1.007-76, the drug “Transfer Factor” can be classified as hazard class IV “Low-hazard substances”.

The effect of hydrophilic statins on adiponectin, leptin, visfatin, and vaspin levels in streptozocin-induced diabetic rats.

Statins may affect glucose metabolism through adipokines. The aim of this study was to measure the effects of hydrophilic statins on the levels of several adipokines in diabetic rats. Wistar albino rats were divided into four groups: healthy control, untreated diabetic, diabetic treated with pravastatin, and diabetic treated with rosuvastatin. Diabetes was induced by intraperitoneal injection of STZ. Thereafter, 20 mg/kg/day doses of either pravastatin or rosuvastatin were administered to the treated diabetic rats for 8 weeks. At the end of the experiment, the body weights, fasting blood glucose levels, serum insulin levels, and insulin resistance, as well as the serum adiponectin, leptin, visfatin, and vaspin levels, were measured. Fasting blood glucose and insulin resistance levels were significantly higher, whereas insulin levels and body weight were significantly lower in the untreated diabetic group than in the control group. Diabetes caused significant decreases in adiponectin, leptin, and vaspin levels but a significant increase in visfatin levels. Pravastatin treatment significantly increased body weight and decreased fasting blood glucose levels, whereas rosuvastatin decreased body weight but did not affect fasting blood glucose levels. Pravastatin caused significant increases in both adiponectin and vaspin levels. However, rosuvastatin did not affect the adiponectin level but caused a significant decrease in the vaspin levels. Both pravastatin and rosuvastatin treatments decreased the leptin and visfatin levels. In conclusion, pravastatin is more effective at improving fasting blood glucose levels and body weight in diabetic rats, probably by increasing adiponectin and vaspin levels.

Male Sprague Dawley Rats with Type 2 Diabetes Mellitus and Obesity on Body Weight, Body Mass Index, and Fat Content as Affected by Alkaloid Fraction of Litsea Glutinosa Leaves (AFLG)

There were 463 million people living with diabetes around the world, and it is expected to increase by 48% in 2045. Dipeptidyl Peptidase 4 (DPP4) inhibitor is asecond-line anti-diabetic drug, that frequently causes weight gain for long term treatment. Alkaloid fraction of L. glutinosa leaves (AFLG) is able to inhibit DPP4 activity in diabetic rats. Therefore, this study aimed to evaluate the effect of AFLG on body weight (BW), BMI, and fat percentage in male rats with model type 2 diabetes mellitus (T2DM) and obesity. Male Sprague Dawley rats, which weighed 200-250 g, were used in this experimental study. Twelve rats were fed with a high-fat diet for 30 days and then were intraperitoneally injected with 230 and 65 mg/kg BW nicotinamide and streptozotocin, respectively. Those rats were randomly divided into 4 groups, control (C) and three treatment (T1-T3) groups, which were orally given 20, 40, and 80 mg/kg BW/day AFLG for 28 days. Collected data were analyzed using a paired t-test, the one-way ANOVA test. Significant differences in BW in T2 and T3 (p = 0.001), Rohrer index in T2 (p = 0.001) and fat content in C (p = 0.013) were observed between before and after treatments. The average of BW, Lee, Rohrer, and TM indexes and fat content in treatment groups did not significantly differ from the C group after 28 days of treatment (p &gt; 0.005). In conclusion, Alkaloid fraction of L. glutinosa leaves does not influence body weight, nutrition status, or fat content of male rats’ models of T2DM and obesity.

The Activation of PKM2 Induces Pyroptosis in Hippocampal Neurons via the NLRP3/Caspase-1/GSDMD Pathway in Neonatal Rats With Hypoxic-Ischemic Brain Injury.

The presence of hypoxic-ischemic brain damage (HIBD) in neonates triggers a strong neuroinflammatory reaction. Pyroptosis, a programmed cell death mechanism associated with inflammation, plays a crucial role in HIBD. Pyruvate kinase M2 (PKM2) plays a significant role in connecting metabolic processes and inflammatory responses, but whether it affects hippocampus pyroptosis in HIBD is unclear. The aim of this study is to elucidate the role of PKM2 in HIBD and to propose a novel therapeutic approach for neonatal ischemic-hypoxic encephalopathy. In this study, we employed neonatal 7-day-old Sprague Dawley rats to establish a model of HIBD using the Rice-Vannucci surgical technique and a hypoxia device. To inhibit the elevation of PKM2, we utilized the PKM2 inhibitor shikonin. The rats were categorized into four groups: Sham, Shikonin, HIBD, and Shikonin+HIBD. Behavioral tests, hematoxylin eosin staining, immunofluorescence staining, ELISA (IL-1β, IL-18), and LDH were conducted in each group to evaluate neurological function, hippocampal damage, the occurrence of neuronal pyroptosis, and the neuroinflammation. Western blot was used to assess the expression levels of PKM2, NLRP3, Caspase-1, Cleaved Caspase-1, GSDMD, GSDMDN, and IL-1β. The expression of PKM2 elevated in hippocampal tissues of the HIBD model and the localization of PKM2 in the hippocampus was activated in neurons instead of microglia during the HIBD. Meanwhile, the inhibition of PKM2 improved the behavioral test scores and the body weight of rats, the neuronal damage in the CA1 region of hippocampal tissue was also attenuated. In addition, inhibiting PKM2 alleviated neuronal pyroptosis by decreasing the expression of PKM2, NLRP3, Caspase-1, Cleaved Caspase-1, GSDMD, GSDMDN. Furthermore, serum levels of LDH and inflammatory factors IL-1β and IL-18 decrease with PKM2 inhibition. Based on these findings, we can conclude that PKM2 plays a crucial role in regulating hippocampal neuronal pyroptosis of HIBD rats via NLRP3/Caspase-1/GSDMD pathway. Therefore, inhibiting PKM2 could be a promising therapeutic strategy for the treatment of neonatal ischemic-hypoxic encephalopathy.

Regulating role of Pleurotus ostreatus insoluble dietary fiber in high fat diet induced obesity in rats based on proteomics and metabolomics analyses

This study aims to reveal the effects of Pleurotus ostreatus insoluble dietary fiber (POIDF) on liver protein and cecal metabolites in obese rats and its potential mechanism by intestinal microbes. It was found that POIDF contained the structural characteristics of cellulose and hemicellulose, as well as amorphous diffraction peaks. POIDF could reduce the body weight and organ index of obese rats, regulate dyslipidemia, and improve the pathological changes of liver and epididymis fat. Further experimental results showed that POIDF could regulate the abundance of bacteria related to lipid metabolism, and maintain intestinal homeostasis. The metabolomics results showed that the fatty acyls pathway in the cecum contents was the pathway with the highest concentration of small molecule metabolites. POIDF supplementation regulated the expression of liver key proteins, as well as biosynthesis of amino acids, steroid biosynthesis, arachidonic acid metabolism and PPAR signaling pathway. Omics association analysis found that POIDF could further regulate liver proteins and their signaling pathways, regulate the levels of fatty acyls and amino acid metabolites in the gut and the enrichment of related pathways, and play a therapeutic or preventive role in obesity after degradation by intestinal microbiota.

Ventral tegmental area amylin / calcitonin receptor signaling suppresses feeding and weight gain in female rats

The pancreatic peptide amylin promotes negative energy balance in part through activation of amylin receptors (AmyRs) expressed in the ventral tegmental area (VTA), but studies have been limited to male rodents. We evaluated whether VTA amylin signaling governs feeding and body weight in female rats. Indeed, pharmacological VTA AmyR activation suppressed chow intake and body weight in females. Viral-mediated knockdown of VTA calcitonin receptor (GPCR of AmyR) supports the physiological relevance of VTA amylin signaling for energy balance control in females. Collectively, these data support the relevance of VTA amylin signaling for energy balance control in both sexes.

Effects of systemic oxytocin and beta-3 receptor agonist (CL 316243) treatment on body weight and adiposity in male diet-induced obese rats.

Previous studies have implicated hindbrain oxytocin (OT) receptors in the control of food intake and brown adipose tissue (BAT) thermogenesis. We recently demonstrated that hindbrain [fourth ventricle (4V)] administration of oxytocin (OT) could be used as an adjunct to drugs that directly target beta-3 adrenergic receptors (β3-AR) to elicit weight loss in diet-induced obese (DIO) rodents. What remains unclear is whether systemic OT can be used as an adjunct with the β3-AR agonist, CL 316243, to increase BAT thermogenesis and elicit weight loss in DIO rats. We hypothesized that systemic OT and β3-AR agonist (CL 316243) treatment would produce an additive effect to reduce body weight and adiposity in DIO rats by decreasing food intake and stimulating BAT thermogenesis. To test this hypothesis, we determined the effects of systemic (subcutaneous) infusions of OT (50 nmol/day) or vehicle (VEH) when combined with daily systemic (intraperitoneal) injections of CL 316243 (0.5 mg/kg) or VEH on body weight, adiposity, food intake and brown adipose tissue temperature (T IBAT ). OT and CL 316243 monotherapy decreased body weight by 8.0±0.9% ( P <0.05) and 8.6±0.6% ( P <0.05), respectively, but OT in combination with CL 316243 produced more substantial weight loss (14.9±1.0%; P <0.05) compared to either treatment alone. These effects were associated with decreased adiposity, energy intake and elevated T IBAT during the treatment period. The findings from the current study suggest that the effects of systemic OT and CL 316243 to elicit weight loss are additive and appear to be driven primarily by OT-elicited changes in food intake and CL 316243-elicited increases in BAT thermogenesis.

The relationship between the results of in silico and in vivo studies of hypoglycemic, hypolipidemic, hepatoprotective properties of a new 1,4-dihydropyridine derivative

Objective: determination of the relationship between the results of in silico and in vivo studies of hypoglycemic, hypolipidemic, hepatoprotective properties of a new 1,4-dihydropyridine derivative coded AZ-383. Material and methods. Virtual bioscreening of compound AZ-383 was carried out using Swiss Target Prediction programs. The identified biotargets were promising for the pharmacocorrection of a complex of metabolic disorders, which was confirmed in an experiment conducted on male Wistar rats. In vivo, the levels of glucose, total cholesterol, triglycer-ides, ALT, AST, and total bilirubin in the blood were studied; the microarchitecture of the rat liver was assessed after pharmacocorrection of simulated metabolic disorders with the compound AZ-383. Results. The presence of hypogly-cemic, hypolipidemic, hepatoprotective activity, and a positive effect on body weight in the compound AZ-383 was revealed. The glucose level reached 7.9±0.4 mmol/l. The body weight of rats after application of AZ-383 was at the level of 378±12 g. Under the influence of AZ-383, an increase in the number of hepatocytes was noted by 17.8%, a decrease in the size of hepatocytes by 7%, a decrease in the area of the cytoplasm and nuclei of hepatocytes by 5.2 and 18.7%, respectively, relative to the control group of animals. Conclusion. An in vivo experiment confirmed the presence of hypoglycemic, hypolipidemic, and hepatoprotective properties in compound AZ-383, which corresponds to the biotargets determined in silico for this 1,4-dihydropyridine derivative.

In Vivo Evaluation of The Hepatotoxic Disorders of Tributyltin Low Doses in Male Rats

Tributyltin (TBT) has been used widely for over 60 years as a pesticidal, preservation, rodent repellent, water-repellant coating, corrosion inhibitor, flame-resistant polyester, and household product. Previous research has demonstrated the toxicity of high doses of TBT, but there is insufficient data on the effects of relevant levels of TBT on at low doses. The main goal of this thesis is to recognize the hepatotoxicity of Sublethal doses of TBT chloride (10-2000 µg/Kg body weight) in male rats for 45 days. TBT induced hepatic induction of oxidative stress as indicated by increasing levels of TBARS and 8-OHdG, induction of hepatic inflammation as indicated by the elevated NF-B levels; inhibition of hepatic expression of PGC-1α and impairment of mitochondrial biogenesis, induction of SREBP-1c and induce hepatic lipogenesis and fatty liver, and distortion of hepatic structure at histological level in a dose-dependent manner significantly at doses higher than 250 µg/kg. In conclusion: the TBT at low doses can induce hepatotoxicity at different levels.

ALLEVIATION OF ARSENIC INDUCED THYROID DYSFUNCTION AND BODY WEIGHT ALTERATIONS BY CURCUMIN

Background: Arsenic is notorious for being used in many homicidal cases. This study was designed to observe the toxic effects of low dose of arsenic on thyroid gland and body weight and its amelioration by curcumin. Method: Thirty healthy female Sprague Dawley rats (body weight ~230 g) were procured from The National Institute of Health Islamabad. After one week of acclimatization, animals were randomly divided into three groups (n=10 each), e.g., Control group (C), Experimental group-1 (E1) and Experimental group-2 (E2). The duration of the experiment was one month. Weight of the animals was checked before and at the end of experiment. All the animals were continued on standard diet and distilled water during experimental period. E1 was given 10 µg/10 mL of arsenic by oral gavage daily. E2 was given 10 µg/10 mL of arsenic along with Curcumin (50 mg/Kg body weight/day). At the end of experiment, the rats were euthanized to draw the blood and removal of thyroid gland. Serum Triiodothyronine, Tetraiodothyronine and Thyroid Stimulating Hormone were measured by ELISA. Histological changes were observed after haematoxylin and eosin staining. Statistical analysis was done on SPSS-22 and p?0.05 was considered significant. Results: The histological findings of thyroid gland, body weight and serum T3, T4 and TSH in E1 exhibited abnormal results. E2 group showed the protecting role of curcumin suggesting protective role of curcumin. Conclusion: Curcumin has protective effects against arsenic induced thyroid disruption and body weight alterations. Pak J Physiol 2024;20(3): DOI: https://doi.org/10.69656/pjp.v20i3.1686

Effects of the aqueous extract of Hibiscus sabdariffa on male fertility and reproductive performance in the rat model

Hibiscus sabdariffa is a popular herb and has long been widely utilised for ethnomedicinal purposes. Despite its benefits, there is very scarce information available on the reproductive toxicity of this plant. The present study aimed to investigate the potential effects of the aqueous extract of H. sabdariffa (AEHS) on the male reproductive system of Sprague Dawley rats. A total of forty males were administered with AEHS at the different dosages of 250, 500, 1000 mg/kg/day or distilled water (control), by oral gavage daily throughout the 60-day treatment periods, which comprised three phases: pre-mating, mating, and post-mating. Results obtained demonstrated that the effects of AEHS on the reproductive system of male rats were slightly significant for certain doses. No mortality and any signs of physical and behavioural toxicity were observed. The mating performance was also not affected. Similarly, the mean body weight of rats was statistically not affected. However, the reproductive organ weights were found to be considerably different. Furthermore, AEHS increased the testosterone levels and sperm counts of the 250 and 1000 mg/kg dose groups, while the 500 mg/kg dose group showed considerably low levels for both parameters. The 500 mg/kg dose group was detected to exhibit inconsistent data for several parameters when compared to other groups, which might be caused by confounding factors instead of AEHS. Therefore, the current data suggest that AEHS should be consumed with caution particularly when the daily dose exceeds 250 mg/kg of body weight.

Utilizing Cinnamomum verum (a culinary spice), as a functional food ingredient ameliorating hypercholesterolemia: In-vivo, in-vitro, and in-silico multi-model analysis

Hypercholesterolemia involves elevated levels of total cholesterol (T.C.), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and reduced high-density lipoprotein (HDL), linked to sedentary lifestyles, irregular eating habits, high-fat diets, type 2 diabetes, and various hereditary and environmental factors. It poses significant health risks, including high blood pressure, atherosclerosis, fatty liver, and cardiovascular disease. This study aimed to evaluate the lipid-lowering effects of ethanolic extract of Cinnamon in hypercholesterolemia-induced rats using in-vivo, in-vitro, and in-silico approaches. In the present work, thirty female Albino rats were divided into six groups: Group I (basal diet), Group II (high-fat diet), Group III (statin treatment), and Groups IV-VI (high-fat diet with different doses of cinnamon extract). Serum lipid profiles were measured after four weeks of treatment. In-vitro HMG-CoA reductase inhibition was assessed. In-silico studies, including molecular docking, ADME analysis, toxicity prediction, and molecular dynamics (M.D.) simulations, were conducted. DFT studies with MESP/HOMO/LUMO analysis provided electronic property insights. High-fat diet increased body weight and serum lipid levels in rats. Cinnamon extract significantly reduces body weight and serum LDL, VLDL, and triglycerides while increasing HDL levels. Histopathology showed reduced fat accumulation and normal liver morphology in cinnamon-treated groups. In-vitro analysis revealed significant HMG-CoA reductase inhibition by cinnamon extract. In-silico docking confirmed strong binding affinities of cinnamon compounds to HMG-CoA reductase. ADME analysis and toxicity prediction indicated favorable pharmacokinetics. MD simulations showed stable ligand-protein complexes, and DFT studies highlighted the electronic properties of active compounds. To conclude, the cinnamon ethanolic extract demonstrated effective lipid-lowering properties in hypercholesterolemic rats, supported by in-vitro and in-silico analyses, suggesting its potential as a therapeutic agent for hypercholesterolemia. Further research is needed to explore underlying mechanisms and clinical outcomes.