Female Rat Model Research Articles

Isoprenaline induced Takotsubo syndrome: Histopathological analyses of female rat hearts.

BackgroundTakotsubo syndrome (TTS) is a stress-induced disorder affecting mostly postmenopausal women. The aim of the study was to evaluate isoprenaline (ISO) dependent female rat model and histopathological characteristics in TTS.MethodsForty-nine Sprague Dawley female rats, 12 weeks old, were injected intraperitoneally with a single dose of ISO at doses 50 (n = 8), 75 (n = 6), 100 (n = 3), 150 (n = 27) and 200 (n = 5) mg/kg body weight (bw). The control group (n = 6) was injected with physiological saline. The echocardiographic examination to assess wall motion abnormalities took place 24, 48, 72 h, and 7 days post-ISO. Histopathological analysis was performed on the basis of hematoxylin-eosin staining.ResultsThe total mortality rate was 3/49 (6.12%). The optimum dose of ISO to induce TTS was 150 mg/kg bw and 21/27 (77.77%) rats showed apical ballooning. Histopathological analysis revealed focal necrosis/apoptosis of cardiomyocytes with inflammatory and fibroblast-like cell infiltration. Foci were the most numerous in the central muscle layer with apical-basal gradient 24, 48, 72 h post-ISO (p < 0.05). Significant differences were noted 48 h post-ISO in the central layer in apical vs basal segments (p = 0.0032), in the endocardial layer in apical vs basal segments (0.00024) and in mid-cavital vs. basal segments (p = 0.0483). The number of foci in endocardium of apical region differ 48 h post-ISO in rats with a dose of 150 vs. 200 mg/kg bw (p = 0.0084).ConclusionsThe ISO female rat model of TTS is associated with higher optimum dose and lower mortality in comparison with the male TTS model. TTS presents as a singles cardiomyocyte disorder, foci concerned mainly central muscle layer with apical-basal gradient.

Puerarin mitigates symptoms of depression in ovariectomized female rats by regulating hippocampal cAMP-CREB-BDNF signaling pathway

Purpose: To investigate the effect of puerarin on the symptoms of depression in ovariectomized female rat model, and the mechanism of action involved.&#x0D; Methods: Ninety healthy female Sprague Dawley (SD) rats were assigned to five groups: sham, model, low-dose puerarin, medium-dose puerarin, and high-dose puerarin groups, with 18 rats per group. Changes in the levels of dopamine (DA), norepinephrine (NA), 5-hydroxytryptamine (5-HT), and apoptosis-related proteins were determined and compared.&#x0D; Results: Compared with the sham group, vertical and horizontal scores, and levels of DA, NA, 5-HT, Bcl-2, p-CREB and BDNF in the model group were significantly decreased. On the other hand, duration of immobility in forced swimming was prolonged, while the concentrations of caspase-1 and ASC increased significantly (p &lt; 0.05). Compared with the model group, with increase in pueraria dose, vertical and horizontal scores, and expression levels of DA, NA, 5-HT, Bcl-2, p-CREB and BDNF of rats were gradually increased, duration of immobility in forced swimming was gradually shortened, and the expression levels of Caspase-1 and ASC w decreased gradually, relative to model group (p &lt; 0.05).&#x0D; Conclusion: Puerarin mitigates depression-like behavior of ovariectomized-depression rats by activating cAMP-CREB-BDNF signaling pathway. Thus, this compound is a potential new lead in the development of drugs for the treatment of depression in ovariectomized women.

Functional and histopathological kidney injury in hyperandrogenic female rats - a polycystic ovary animal model

Background. Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in premenopausal women. This syndrome is also associated with many metabolic and cardiovascular complications. These complications are major risk factors for renal injury and kidney disease. Therefore, this study aimed to investigate the types of functional and structural kidney injuries in a hyperandrogenic female rat model. Methods. Female Sprague-Dawley rats were randomly divided into three groups (n=10 each): control, sham, and dehydroepiandrosterone (DHEA). Plasma total testosterone and kidney functional indices were measured using enzyme-linked immunosorbent assay (ELISA) and colorimetric techniques. Ovarian and renal histological changes were also evaluated qualitatively and quantitatively by Hematoxylin-Eosin (H&amp;E) staining. Results. Plasma total testosterone in the DHEA group increased about 9-fold compared to the control and sham groups. There was also a significant increase in Cr, BUN, and absolute excretion of sodium ion. Insignificant increases in glomerular filtration rate (GFR), urine flow rate (V0), and absolute excretion of potassium ion were observed in DHEA group compared to other groups. However, significant damages were observed in the glomerular and tubular parts of the kidneys and the follicular parts of the ovaries in DHEA-receiving rats. Conclusion. Hyperandrogenemia is likely to cause systemic abnormalities through a variety of mechanisms, followed by obvious destruction of kidney and ovarian tissues. Accordingly, DHEA administration provides a useful animal model for studying the mechanism of PCOS-mediated renal injury. Practical Implications. The present study Findings can be helpful in identifying the mechanism of PCOS-induced renal injury, especially in younger women.

Therapeutic effects of silver nanoparticles on Escherichia coli-induced endometritis in rats

Background Silver nanoparticles (AgO-NPs) have shown antimicrobial effects against a broad spectrum of microorganisms.Objectives To assess the antimicrobial effects of AgO-NPs prepared using an eco-friendly green method against multidrug-resistant Escherichia coli in vivo after inducing endometritis in rats.Materials and methods In female mice, LD50 of AgO-NPs was determined, followed by a chronic toxicity in female rats by oral administration of 0, 20, 30, and 40 mg of AgO-NPs daily for 4 weeks. The induced endometritis model in female rats was performed by inoculating two doses of E. coli (100 μl of 10×105 CFU) intravaginally. Seven days later, vaginal swabs were stained with Wright stain to confirm the development of endometritis and used to re-isolate the inoculated microorganism. Two doses of 100 μl containing 10 mg AgO-NPs were inoculated intravaginally. Estradiol, progesterone, liver and kidney functions, oxidants and antioxidants, and zinc were measured in collected blood samples of chronic toxicity and induced endometritis model.Results and conclusion LD50 of AgO-NPs was 800 mg/kg body weight (BW). The use of 40 (1 : 20 LD50), 30 (1 : 26.67 LD50), and 20 (1 : 40 LD50) mg/kg BW during the chronic toxicity experiment was safe as indicated by blood biochemical analyses. The chronic toxicity experiment resulted in normal liver and kidney functions, oxidant–antioxidant status, acute-phase proteins, and ovarian hormones. The green method-synthesized AgO-NPs showed efficacy against E. coli-induced endometritis, and rats responded to the treatment as indicated by the uterine cytology and the clinical analysis with mild adverse effects on both liver and kidney. In conclusion, AgO-NPs showed treatment of experimental uterine infections induced by E. coli in rats and were safe for longer administration in concentrations lower than 50 mg/kg BW.

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

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

Antitumor and Antibacterial Efficacy of Gallium Nanoparticles Coated by Ellagic Acid.

Cancer is a mortality contributor worldwide, and breast cancer is the most common among women. Despite the numerous breast cancer therapeutic strategies, they either have limitations or sometimes are resisted by cancer, so new approaches are needed to tackle those restrictions. Nanotechnology offers exciting leaps in the diagnosis and treatment of cancer, especially breast cancer. The main objective of this study was to investigate the effect of the newly synthesized gallium nanoparticles coated by Ellagic acid (EA-GaNPs) on the induced mammary gland carcinogenesis in female rats and their antibacterial activities comparison with standard antibiotics (Ketoconazole (100 μg/ml) and Gentamycin (4 μg/ml)) by disc diffusion method using eight different microbial species. The antitumor efficacy of EA-GaNPs was conducted both in vitro and in in vivo. The result of antimicrobial activity of EA-Ga NPs (1 mg/1 mL) revealed moderate toxicity behavior against Gram-positive {Staphylococcus aureus, Bacillus subtilis, Bacillus cereus) and Gram-negative pathogenic bacteria {Escherichia coli, Proteus vulgarfs) also, antifungal activity was detected against {Aspergillus terreus). In vitro study showed that EA-GaNPs inhibited human breast cancer cell line (MCF-7) proliferation with IC50 of 2.86 μg/ml. Although in vivo; the administration of EA-GaNPs to DMBA-treated rats ameliorated the hyperplastic state of mammary gland carcinogenesis induced by DMBA. Additionally, EA-GaNPs administration significantly modulated the activities of ALT and AST, as well as the levels of urea and creatinine in serum. Also, EA-GaNPs administration improved the antioxidant state by increasing Superoxide dismutase activity and GSH content, and decreasing malondialdehyde content in the mammary tissue, besides enhancing the apoptotic activity through elevating the levels of caspase-3 and decreasing the protein intensities of protein kinase B & phosphatidyl inositide 3-kinases. Furthermore, a significant decrease in serum Total iron-binding capacity accompanied by a significant increase in the level of calcium was noted. So, it can be concluded that the newly synthesized nanoparticles EA-GaNPs have an efficient antitumor activity that was manifested by reduction of the viability on the human breast cancer cell line (MCF-7) in vitro. Also, in vivo against the chemically induced mammary gland carcinogenesis in a female rat model. Histopathological findings were in harmony with biochemical and molecular results showing the effectiveness of EA-GaNPs against mammary carcinogenesis. Therefore, EA-GaNPs could be a promising, potent anti-cancer compound.

The Effect of the Angiotensin-Converting Enzyme Inhibitor on Bone Health in Castrated Hypertensive Rats Is Mediated via the Kinin-Kallikrein System

Background In previous studies, angiotensin-converting enzyme inhibitor (ACEI) use was associated with increased bone loss, while an angiotensin II type I receptor blocker had no effect on bone loss in elder subjects, which suggested that the effect of ACEI on bone loss was not mediated through the classical renin-angiotensin system. In this study, we set to investigate whether the effect of ACEI on bone deterioration was mediated via the kinin-kallikrein system. Methods Six-month-old male and female spontaneously hypertensive rats were used. The effect of captopril on blood pressure, serum Ang II, and bradykinin concentration was measured in intact rats. Ovariectomy and orchidectomy were performed to establish an osteoporosis model in female and male rats, respectively. Captopril and the bradykinin receptor blocker icatibant (HOE140) were administered after operation for 12 weeks. Serum Ang II and bradykinin concentration, bone turnover markers, bone mineral density (BMD), and bone microarchitecture were evaluated. Femur samples were subjected to a mechanical test. Results Captopril decreased blood pressure and serum Ang II concentration and increased serum bradykinin concentration in intact rats (P < 0.05). After castration, captopril decreased serum Ang II concentration (P < 0.05); in female rats, icatibant increased serum Ang II concentration (P < 0.05). Captopril increased serum bradykinin concentration (P < 0.05); in male rats, icatibant decreased serum bradykinin concentration (P < 0.05). Captopril increased the rat urine deoxypyridinoline-creatinine ratio (DPD/Cr) and serum osteocalcin concentration (P < 0.05). Icatibant decreased urine DPD/Cr in male rats (P < 0.05) and increased osteocalcin concentration in female rats (P < 0.05). Captopril increased cancellous BMD in castrated hypertensive rats (P < 0.05), and icatibant further increased cancellous BMD (P < 0.05), which was due to the increased trabecular bone number. In mechanical testing, ACEI increased bone strength (P < 0.05), and icatibant further improved it (P < 0.05). Conclusion ACEI decreased bone deterioration in both male and female hypertensive rats, and the bradykinin receptor blocker further decreased bone deterioration.

The Therapeutic Effect of Methanolic Extract Bryonia dioica Jacq. in a Female Rat Model of Polycystic Ovary Syndrome

Objective: Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases that affects 5%–10% of women of childbearing age. Several factors contribute to the development of PCOS such as dysfunction of the hypothalamic–pituitary axis and ovarian function, as well as increased insulin levels. The manifestations of the disorder include a wide range of symptoms, including menstrual disorders, acne, infertility, and increased body fat. Currently, the most well-known treatments for PCOS are clomiphene, metformin, letrozole, and tamoxifen. Due to their side effects, the identification of substitute drugs is essential. One of the traditional medicines, which is usually used in different parts of the world, particularly in Western Europe, is Bryonia dioica Jacq. (B. dioica). This plant is used in the treatment of disease due to its active ingredients like polyphenols. Materials and Methods: Induction PCOS in a female rat (3 weeks old) was performed through subcutaneous injection of testosterone enanthate (1 mg/100g) daily for 35 days. The effects of B. dioica (30 and 60 mg/kg) root methanolic extract on PCOS-induced was evaluated after 28-day treatment. On the last day, the serum levels of follicle-stimulating hormone (FSH), glucose, low-density lipoprotein/high-density lipoprotein (LDL/HDL), luteinizing hormone (LH), and testosterone and histological studies (hematoxylin and eosin [H&amp;E] staining) were measured. Results: Results showed that FSH and LH levels (P &lt; 0.05) as well as glucose (P &lt; 0.001) in the B. dioica groups normalized significantly compared to the PCOS group. LDL levels decreased in rats and the LDL/HDL ratio decreased in all treatment groups. In histologic assay, metformin and B. dioica restricted the effects of testosterone in the ovaries of rats. Conclusion: The data indicate that methanolic extract of B. dioica recovers hormonal factors in PCOS.

A Model in Female Rats With Phenotypic Features Similar to Interstitial Cystitis/Bladder Pain Syndrome.

This report describes methodological and exploratory investigations of the zymosan-induced neonatal bladder inflammation (NBI) model of interstitial cystitis/bladder pain syndrome (IC/BPS) in female rats. These results validate and extend the currently employed model by evaluating critical timepoints for obtaining treatment effects and identified that a second insult as an adult including repeat intravesical zymosan, intravesical lipopolysaccharide, acute footshock stress, neuropathic nociception (facial) or somatic inflammation (hindpaw) all resulted in magnified visceromotor responses to urinary bladder distension (UBD) in rats which had experienced NBI when compared with their controls. NBI also resulted in increased tone and reactivity of pelvic floor musculature to UBD, as well as increased responsiveness to intravesical potassium chloride solutions, abnormal anxiety measures (elevated plus maze) and an increased number of submucosal petechial hemorrhages following 30 min of hydrodistension of the bladder. These phenotypic findings have correlates to the clinical features of IC/BPS in humans and so support use of this model system to examine mechanisms of and treatments for IC/BPS.

Treatment with sodium (S)-2-hydroxyglutarate prevents liver injury in an ischemia-reperfusion model in female Wistar rats

BackgroundIschemia-reperfusion (IR) injury is one of the leading causes of early graft dysfunction in liver transplantation. Techniques such as ischemic preconditioning protect the graft through the activation of the hypoxia-inducible factors (HIF), which are downregulated by the EGLN family of prolyl-4-hydroxylases, a potential biological target for the development of strategies based on pharmacological preconditioning. For that reason, this study aims to evaluate the effect of the EGLN inhibitor sodium (S)-2-hydroxyglutarate [(S)-2HG] on liver IR injury in Wistar rats.MethodsTwenty-eight female Wistar rats were divided into the following groups: sham (SH, n = 7), non-toxicity (HGTox, n = 7, 25 mg/kg of (S)-2HG, twice per day for two days), IR (n = 7, total liver ischemia: 20 minutes, reperfusion: 60 minutes), and (S)-2HG+IR (HGIR, n = 7, 25 mg/kg of (S)-2HG, twice per day for two days, total liver ischemia as the IR group). Serum ALT, AST, LDH, ALP, glucose, and total bilirubin were assessed. The concentrations of IL-1β, IL-6, TNF, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured in liver tissue, as well as the expression of Hmox1, Vegfa, and Pdk1, determined by RT-qPCR. Sections of liver tissue were evaluated histologically, assessing the severity of necrosis, sinusoidal congestion, and cytoplasmatic vacuolization.ResultsThe administration of (S)-2HG did not cause any alteration in the assessed biochemical markers compared to SH. Preconditioning with (S)-2HG significantly ameliorated IR injury in the HGIR group, decreasing the serum activities of ALT, AST, and LDH, and the tissue concentrations of IL-1β and IL-6 compared to the IR group. IR injury decreased serum glucose compared to SH. There were no differences in the other biomarkers assessed. The treatment with (S)-2HG tended to decrease the severity of hepatocyte necrosis and sinusoidal congestion compared to the IR group. The administration of (S)-2HG did not affect the expression of Hmox1 but decreased the expression of both Vegfa and Pdk1 compared to the SH group, suggesting that the HIF-1 pathway is not involved in its mechanism of hepatoprotection. In conclusion, (S)-2HG showed a hepatoprotective effect, decreasing the levels of liver injury and inflammation biomarkers, without evidence of the involvement of the HIF-1 pathway. No hepatotoxic effect was observed at the tested dose.

Truncated Milk Fat Globule-EGF-like Factor 8 Ameliorates Liver Fibrosis via Inhibition of Integrin-TGFβ Receptor Interaction

Milk fat globule-EGF factor 8 (MFG-E8) protein is known as an immunomodulator in various diseases, and we previously demonstrated the anti-fibrotic role of MFG-E8 in liver disease. Here, we present a truncated form of MFG-E8 that provides an advanced therapeutic benefit in treating liver fibrosis. The enhanced therapeutic potential of the modified MFG-E8 was demonstrated in various liver fibrosis animal models, and the efficacy was further confirmed in human hepatic stellate cells and a liver spheroid model. In the subsequent analysis, we found that the modified MFG-E8 more efficiently suppressed transforming growth factor β (TGF-β) signaling than the original form of MFG-E8, and it deactivated the proliferation of hepatic stellate cells in the liver disease environment through interfering with the interactions between integrins (αvβ3 & αvβ5) and TGF-βRI. Furthermore, the protein preferentially delivered in the liver after administration, and the safety profiles of the protein were demonstrated in male and female rat models. Therefore, in conclusion, this modified MFG-E8 provides a promising new therapeutic strategy for treating fibrotic diseases.

7: Reduced trabecular bone growth in an adolescent female cystic fibrosis rat model

7: Reduced trabecular bone growth in an adolescent female cystic fibrosis rat model

Basolateral amygdala corticotropin-releasing factor receptor type 1 regulates context-cocaine memory strength during reconsolidation in a sex-dependent manner

The basolateral amygdala (BLA) is a critical brain region for cocaine-memory reconsolidation. Corticotropin-releasing factor receptor type 1 (CRFR1) is densely expressed in the BLA, and CRFR1 stimulation can activate intra-cellular signaling cascades that mediate memory reconsolidation. Hence, we tested the hypothesis that BLA CRFR1 stimulation is necessary and sufficient for cocaine-memory reconsolidation. Using an instrumental model of drug relapse, male and female Sprague-Dawley rats received cocaine self-administration training in a distinct environmental context over 10 days followed by extinction training in a different context over 7 days. Next, rats were re-exposed to the cocaine-paired context for 15 min to initiate cocaine-memory retrieval and destabilization. Immediately or 6 h after this session, the rats received bilateral vehicle, antalarmin (CRFR1 antagonist; 500 ng/hemisphere), or corticotropin-releasing factor (CRF; 0.2, 30 or 500 ng/hemisphere) infusions into the BLA. Resulting changes in drug context-induced cocaine seeking (index of context-cocaine memory strength) were assessed three days later. Female rats self-administered more cocaine infusions and exhibited more extinction responding than males. Intra-BLA antalarmin treatment immediately after memory retrieval (i.e., when cocaine memories were labile), but not 6 h later (i.e., after memory reconsolidation), attenuated drug context-induced cocaine seeking at test independent of sex, relative to vehicle. Conversely, intra-BLA CRF treatment increased this behavior selectively in females, in a U-shaped dose-dependent fashion. In control experiments, a high (behaviorally ineffective) dose of CRF treatment did not reduce BLA CRFR1 cell-surface expression in females. Thus, BLA CRFR1 signaling is necessary and sufficient, in a sex-dependent manner, for regulating cocaine-memory strength.

Unveiling antioxidant and anti-cancer potentials of characterized Annona reticulata leaf extract in 1,2-dimethylhydrazine-induced colorectal cancer in Wistar rats

BackgroundColorectal cancer (CC) is the third most common cancer in the world. Annona reticulata (AR) also known as bullock's heart, is a traditional herb. AR leaf extract was initially investigated for its anti-bacterial, anti-inflammatory, anti-malarial, anti-helminthic, anti-stress, and wound healing properties. Only a few in vitro cancer studies have been conducted on AR. Although few studies have linked AR leaf extract to many cancers, comprehensive studies addressing regulation, biological functions, and molecular mechanisms leading to CC pathogenesis are clearly lacking. ObjectivesThe present study aimed to explore the antioxidant and anti-cancer potentials of AR leaf extract in CC. Materials and methodsThe MTT assay was used to test the anti-proliferative activity of AR leaf extract in vitro on the HCT116 cell line. Qualitative and quantitative phytochemical characterization was carried out using gas chromatography: mass spectrometry (GC–MS). 1,2-dimethylhydrazine (DMH) was used to establish CC model in female Wistar rats. The acute toxicity of AR leaf extract was tested in accordance with OECD guidelines. Aberrant Crypt Foci (ACF) count, organ index, and hematological estimations were used to screen for in vivo anti-cancer potential. The antioxidant activity of colon homogenate was determined. ResultsThe alcoholic leaf extract (IC50, 0.55 μg/ml) was found to be more potent than the aqueous extract. Using GC–MS, a total of 108 compounds were quantified in the alcoholic leaf extract. The LD 50 value was found to be safe at a dose of 98.11 mg/kg of body weight. AR alcoholic leaf extract significantly (p < 0.05) decreased ACF count and normalized colon length/weight ratio. AR leaf extract increased RBC, hemoglobin and platelets levels. The AR alcoholic leaf extract reduced the DMH-induced tumors and significantly (p < 0.05) increased the activity of endogenous antioxidant enzymes such as catalase, reduced glutathione, superoxide dismutase, and decreased the lipid peroxidase activity. AR leaf extract reduced the inflammation caused by DMH and helped to repair the colon's damaged muscle layers. ConclusionBased on the findings from the present study, it can be concluded that the alcoholic leaf extract of AR has antioxidant and anti-proliferative properties and can aid in the prevention of CC development and dysplasia caused by DMH.

Development and Evaluation of Curcumin Encapsulated Self-assembled Nanoparticles as Potential Remedial Treatment for PCOS in a Female Rat Model.

PurposePolycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women of reproductive age and leads to metabolic disorders and infertility. The present study was conducted to investigate the therapeutic effects of curcumin (Cur) encapsulated arginine (Arg) and N-acetyl histidine (NAcHis) modified chitosan (Arg-CS-NAcHis/Cur) nanoparticles (NPs).MethodsIn this study, amphiphilic chitosan (CS) conjugate was developed by modification with hydrophilic arginine (Arg) and hydrophobic N-acetyl histidine (NAcHis) group (Arg-CS-NAcHis). The synthesized conjugate was well characterized by FTIR and NMR studies. Self-assembled nanoparticles based on the synthesized conjugate were developed by simple sonication method and characterized for the physicochemical properties of zeta potential, particle size and drug encapsulation. Next, in vitro drug release, cytotoxicity, and cellular uptake studies of the NPs were evaluated. Finally, the developed nanoparticles were examined for their therapeutic potential against estradiol valerate (EV) induced PCOS rats by evaluating hormone level changes and ovarian morphology.ResultsThe results showed that zeta potential of the nanoparticles was 39.8±2.52 mV and the average size was 200 nm. The in vitro drug release profile showed sustained release pattern. Cytotoxicity and cellular uptake studies also showed preferential effectiveness than free curcumin. Both the biochemical and histopathological studies showed positive effects in reverting the symptoms of PCOS rats to normalcy.ConclusionCurcumin encapsulated arginine and N-acetyl histidine modified chitosan (Arg-CS-NAcHis/Cur) nanoparticles have been successfully developed. The present study suggested that treatment of the nanoparticles might reverse many of the PCOS symptoms. Therefore, these nanoparticles might be used as promising new candidate for delivery of curcumin to treat PCOS.

Carotenoid-Enriched Fractions From Spondias mombin Demonstrate HER2 ATP Kinase Domain Inhibition: Computational and In Vivo Animal Model of Breast Carcinoma Studies.

Human epidermal growth factor 2 (HER2) is overexpressed in about 20% of breast cancer and is associated with a poor prognosis. We report in this study that carotenoid-enriched fractions from Spondias mombin demonstrate HER2 ATP kinase domain inhibition. HER2 breast carcinoma was modeled in female Wistar rats and authenticated via immunohistochemical studies. Inhibition of HER2 ATP kinase domain by the carotenoid-enriched fractions was investigated by molecular docking, atomistic simulation, and the expression of HER2 mRNA in HER2-positive breast carcinoma model in female Wistar rats. The therapeutic efficacy of the treatments (carotenoid-rich fractions) was determined by biochemical, tumor volume, and histopathological analysis. Immunohistochemical analysis revealed 7,12-dimethylbenz[a]anthracene (DMBA)-induced HER2-positive breast carcinoma. Phytoconstituents of the carotenoid-enriched fractions astaxanthin, 7,7′,8,8′-tetrahydro-β,β-carotene, beta-carotene-15,15′-epoxide, and lapatinib (standard drug) demonstrate inhibition of HER2 with docking scores of −3.0, −8.5, −11.5, and −10.6 kcal/mol, respectively; and during atomistic simulation, the compounds ruptured the canonical active-state K753/E770 salt-bridge interaction. The treatment similarly downregulated HER2 mRNA expression significantly at p < 0.05. It also upregulated the expression of p53 and p27 mRNAs significantly at p < 0.05 and reduced creatinine and urea concentrations in the serum at p < 0.05. The tumor volume was also significantly reduced when compared with that of the untreated group. Carotenoid-enriched fractions from S. mombin demonstrate anti-HER2 positive breast carcinoma potentials via HER2 ATP kinase domain inhibition.

Adolescent female rats prone to the activity based anorexia (ABA) paradigm have altered hedonic responses and cortical astrocyte density compared to resistant animals

ObjectiveAnhedonia, which in part involves the lack of pleasure in consuming palatable food, is a long-lasting symptom observed in patients both when acutely ill and when long term recovered from Anorexia Nervosa. The neurocircuitry underlying this phenomenon is not well understood. Here we use the preclinical activity-based anorexia (ABA) model in adolescent female rats to assess the impact of excessive exercise, limited food intake and acute weight loss, on adolescent female rat orofacial responding to intraoral sucrose, as measured by the taste reactivity test (TRT). Animals were identified as either prone or resistant to this paradigm based on a weight loss criterion. Measures of food intake, running wheel activity, taste reactivity and medial prefrontal cortex astrocyte expression were compared across groups. MethodsAdolescent female rats implanted with an intraoral catheter were given a TRT using 1 M (M) sucrose at baseline, max weight loss (25% weight loss from start of ABA or 7 full days on the paradigm) or 10 days recovered from the ABA paradigm. Animals were sacrificed after the final TRT and astrocyte density was measured via immunohistochemistry. ResultsAnimals resistant to the ABA paradigm ran less than prone animals during the ABA period. Additionally, we found that resistant animals displayed more cumulative ‘liking’ responses to sucrose compared to prone animals at maximum weight loss. Finally, we found prone animals 10-days recovered from ABA had reduced medial prefrontal cortex astrocyte density compared to levels in resistant animals. DiscussionRats presented with the physiological challenge of the ABA paradigm either adapt their behavior to stabilize their body weight (i.e. resistant), or rapidly lose weight (i.e. prone). Furthermore, we found that prone animals have reduced orofacial responding to 1 M sucrose at maximum weight loss compared to responses in resistant animals, and this anhedonia-like behavior may be a result of reduced astrocyte density that affects cortical function.

Long Term Effects of Streptozotocin Induced Diabetes Mellitus on Hepatic, Nephrotic and Cardiac Physiology of Female Wistar Rats

Background: Diabetes mellitus is a metabolic disorder which leads to complications that affect the heart, kidney, liver and other vital organs. Most reports on diabetes have focused on diabetes induction using male rat models in short term studies.Objective: Here, we described the induction of diabetes in female rat and the complications of diabetes following long term hyperglycemia in female Wistar rats.Method: Rats were assigned into two groups: control (n=10) and diabetic (n=10). The latter was administered a single (50mg/Kg body weight) intraperitoneal injection of streptozotocin. Bodyweight and blood glucose were assessed for 14 weeks, after which the animals were sacrificed and biochemical and morphology parameters of the liver, kidney and heart were determined.Results: Diabetic rats showed continuous emaciation post STZ induction. The glycated haemoglobin, protein level, lipid profile, liver and kidney function markers were significantly different (p&lt;0.05) from the control. Catalase, superoxide dismutase and glutathione-s-transferase activities were also significantly reduced in the heart, liver and kidney, and a concomitant increase in malondialdehyde concentration was observed. Focal tubular necrosis, pulmonary congestion and mild hyperplasia of kupffer cells were observed in the tissues and all tissues showed negative CD79a expression.Conclusion: This study provides data that could be useful for modelling long-term diabetes mellitus studies in female experimental rat models.

Impact of selenium on cerebellar injury and mRNA expression in offspring of rat exposed to methylmercury

During the fetal development stage, the Central Nervous System (CNS) is particularly sensitive to methylmercury (MeHg). However, the mechanism underlying the antagonistic effect of selenium (Se) on MeHg toxicity is still not fully understood. In this study, female rat models with MeHg and Se co-exposure were developed. Pathological changes in the cerebellum and differential mRNA expression profiles in offspring rats were studied. In the MeHg-exposed group, a large number of Purkinje cells showed pathological changes and mitochondria were significantly swollen; co-exposure with Se significantly improved the structure and organization of the cerebellum. In total, 378 differentially expressed genes (DEGs) (including 284 up-regulated genes and 94 down-regulated genes) in the cerebellum of the MeHg-exposed group and 210 DEGs (including 84 up-regulated genes and 126 down-regulated genes) in the cerebellum of the MeHg+Se co-exposed group were identified. The genes involved in neurotransmitter synthesis and release and calcium ion balance in the cerebellum were significantly up-regulated in the MeHg-exposed group. These genes in the MeHg+Se co-exposed group were not changed or down-regulated. These findings demonstrate that the neurotoxicity caused by MeHg exposure is related to the up-regulation of multiple genes in the nerve signal transduction and calcium ion signal pathways, which are closely related to impairments in cell apoptosis and learning and memory. Supplementation with Se can mitigate the changes to related genes and protect neurons in the mammalian brain (especially the developing cerebellum) from MeHg toxicity. Se provides a potential intervention strategy for MeHg toxicity.

Heterogeneity in patterns of pain development after nerve injury in rats and the influence of sex

The genesis of neuropathic pain is complex, as sensory abnormalities may differ between patients with different or similar etiologies, suggesting mechanistic heterogeneity, a concept that is largely unexplored. Yet, data are usually grouped for analysis based on the assumption that they share the same underlying pathogenesis. Sex is a factor that may contribute to differences in pain responses. Neuropathic pain is more prevalent in female patients, but pre-clinical studies that can examine pain development in a controlled environment have typically failed to include female subjects. This study explored patterns of development of hyperalgesia-like behavior (HLB) induced by noxious mechanical stimulation in a neuropathic pain model (spared nerve injury, SNI) in both male and female rats, and autonomic dysfunction that is associated with chronic pain. HLB was analyzed across time, using both discrete mixture modeling and rules-based longitudinal clustering. Both methods identified similar groupings of hyperalgesia trajectories after SNI that were not evident when data were combined into groups by sex only. Within the same hyperalgesia development group, mixed models showed that development of HLB in females was delayed relative to males and reached a magnitude similar to or higher than males. The data also indicate that sympathetic tone (as indicated by heart rate variability) drops below pre-SNI level before or at the onset of development of HLB. This study classifies heterogeneity in individual development of HLB and identifies sexual dimorphism in the time course of development of neuropathic pain after nerve injury. Future studies addressing mechanisms underlying these differences could facilitate appropriate pain treatments.