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  1. Purified ingredient-based high-fat diet is superior to chow-based equivalent in the induction of metabolic syndrome
    Cheng HS, Phang SCW, Ton SH, Abdul Kadir K, Tan JBL
    J Food Biochem, 2019 02;43(2):e12717.
    PMID: 31353646 DOI: 10.1111/jfbc.12717
    The present study aimed to outline the physiological and metabolic disparity between chow- and purified ingredient-based high-fat diets and their efficacy in the induction of metabolic syndrome (MetS). Male, 3-week-old Sprague Dawley rats were randomly assigned to chow-based control diet, chow-based high-fat diet, purified control diet, and purified high-fat diet for 12 weeks. Physical and biochemical changes were documented. Chow-based diets, irrespective of the lipid content, resulted in significantly lower weight gain and organ weight compared to purified ingredient-based diets. Circulating insulin, total proteins, albumin, and certain lipid components like the triglycerides, total cholesterol, and high-density lipoprotein-cholesterol were also lower in the chow-based diet groups. Both chow- and purified high-fat diets induced central obesity, hypertension, and hyperglycaemia, but the latter was associated with earlier onset of the metabolic aberrations and additionally, dyslipidaemia. In conclusion, purified high-fat diet is a better diet for MetS induction in rats. PRACTICAL APPLICATIONS: Modeling metabolic syndrome is commonly accomplished with the use of chow- or purified ingredient diets enriched with carbohydrates and/or lipids, but the differences and associated drawbacks are unclear. This study highlights that chow- or modified chow-based diets have a tendency to introduce unwanted metabolic changes which are inconsistent with the progression of metabolic syndrome. Thus, the use of these diets in metabolic disease study should be avoided. On the other hand, purified high-fat diet which can effectively induce the features of metabolic syndrome is highly recommended.
    Matched MeSH terms: Rats, Sprague-Dawley
  2. Leptin enhances N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced tumour growth in gastric mucosa of male Sprague-Dawley rats
    Isyraqiah F, Kutty MK, Durairajanayagam D, Singh HJ
    Mol Biol Rep, 2019 Dec;46(6):5967-5975.
    PMID: 31444698 DOI: 10.1007/s11033-019-05030-z
    Individuals who are obese are at a greater risk of developing gastric cancer. They are however also hyperleptinaemic. Chronic leptin treatment has been shown to upregulate numerous cancer-causing genes in the stomach of male Sprague-Dawley rats. It is however unclear if leptin enhances the effect of gastric carcinogens in vivo. This study was therefore done to investigate the effect of leptin on gastric carcinogenesis in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Twenty-four, 6-week old male Sprague-Dawley rats were divided equally into three groups: G1 served as age-matched controls; G2 was treated with MNNG in drinking water ad libitum (200 mg L-1); G3 was given leptin and MNNG. Rats were euthanized after 40 weeks of treatment and their stomachs were removed for histopathology, microarray, and RT-qPCR analysis. Fisher's exact test and one-way ANOVA were used to analyse the data. Fifty percent of the MNNG-treated rats developed gastric hyperplasia (p 
    Matched MeSH terms: Rats, Sprague-Dawley
  3. Fulltext The differential roles of caspase family members in mediating PF4-induced breast cancer apoptosis
    Tengku Din TADAA, Abdul Jalal MI, Seeni A, Shamsuddin S, Jaafar H
    Malays J Pathol, 2018 Dec;40(3):303-312.
    PMID: 30580361
    INTRODUCTION: This study focused on PF4 effects on caspase-3,-6, -7, -8 and -9 which regulate the apopotosis process in breast cancer.

    MATERIALS AND METHODS: Breast tumours were induced in forty 21-day-old female Sprague Dawley rats (SDRs) using MNU until tumour size reached 14.5 mm (SD: 0.5 mm). The rats were then divided into two groups: Group 1 (control injected with 0.9% saline; n = 20), and Group 2 (platelet factor 4 (PF4); n = 20). PF4 was administered through focal intralesional injection at 20 μg/lesion dose. Following 5-day treatment, the SDRs were sacrificed. Subsequently, representative sections from the tumour were obtained for haematoxylin and eosin (H&E) staining. The expressions of caspase-3, -6, -7, -8 and -9 were evaluated using immunohistochemistry (IHC) staining.

    RESULTS: The majority of breast tumour specimens were of aggressive types [ncontrol = 13 (65%); nPF4 = 12 (60%)]. Invasive ductal carcinoma not otherwise specified (IDC-NOS) was the most commonly observed breast tumour histology for control and PF4 groups (n = 8 (40%) in respective groups). PF4-treated group exhibited significant differences in the caspase-3, -6 and -8 expression levels compared to the control group (all p < 0.001). There were no significant differences in caspase-7 (p = 0.347) and caspase-9 (p = 0.373) expression levels between both groups.

    CONCLUSION: This study found that PF4 acts via the caspase-mediated extrinsic apoptosis pathway without the involvement of the intrinsic pathway.
    Matched MeSH terms: Rats, Sprague-Dawley
  4. Marantodes pumilum (Blume) Kuntze (Kacip Fatimah) stimulates uterine contraction in rats in post-partum period
    Wan Omar WFN, Giribabu N, Karim K, Salleh N
    J Ethnopharmacol, 2019 Dec 05;245:112175.
    PMID: 31442621 DOI: 10.1016/j.jep.2019.112175
    ETHNOPHARMACOLOGICAL RELEVANCE: Marantodes pumilum (Blume) Kuntze has traditionally been used to firm the uterus after delivery, however scientific evidences behind this claim is still lacking.

    AIMS OF STUDY: To demonstrate Marantodes pumilum leaves aqueous extract (MPE) has an effect on uterine contraction after delivery and to elucidate the molecular mechanisms involved.

    METHODS: Day-1 post-delivery female rats were given MPE (100, 250 and 500 mg/kg/day) orally for seven consecutive days. A day after the last treatment (day-8), rats were sacrificed and uteri were harvested and subjected for ex-vivo contraction study using organ bath followed by protein expression and distribution study by Western blotting and immunohistochemistry techniques, respectively. The proteins of interest include calmodulin-CaM, myosin light chain kinase-MLCK, sarcoplasmic reticulum Ca2+-ATPase (SERCA), G-protein α and β (Gα and Gβ), inositol-triphosphate 3-kinase (IP3K), oxytocin receptor-OTR, prostaglandin (PGF)2α receptor-PGFR, muscarinic receptor-MAChR and estrogen receptor (ER) isoforms α and β. Levels of estradiol and progesterone in serum were determined by enzyme-linked immunoassay (ELISA).

    RESULTS: Ex-vivo contraction study revealed the force of uterine contraction increased with increasing doses of MPE. In addition, expression of CaM, MLCK, SERCA, Gα, Gβ, IP3K, OTR, PGF2α, MAChR, Erα and ERβ in the uterus increased with increasing doses of MPE. Serum analysis indicate that estradiol levels decreased while progesterone levels remained low at day-8 post-partum in rats receiving 250 and 500 mg/kg/day MPE.

    CONCLUSIONS: These findings support the claims that MPE help to firm the uterus and pave the way for its use as a uterotonic agent after delivery.

    Matched MeSH terms: Rats, Sprague-Dawley
  5. Determining weight-bearing tissue condition using peak reactive hyperemia response trend and ultrasonographic features: Implications for pressure ulcer prevention
    Yapp JH, Raja Ahmad RMK, Mahmud R, Mohtarrudin N, Mohamad Yusof L, Abdul Rahim E, et al.
    Wound Repair Regen, 2019 05;27(3):225-234.
    PMID: 30667138 DOI: 10.1111/wrr.12698
    Frequent repositioning is important to prevent pressure ulcer (PU) development, by relieving pressure and recovering damages on skin areas induced by repetitive loading. Although repositioning is the gold standard to prevent PU, there is currently no strategy for determining tissue condition under preventive approaches. In this study, the peak reactive hyperemia (RH) trends and ultrasonographic (US) features are compared with the tissue condition under histopathological examination to determine the potential use of these features in determining the tissue condition noninvasively. Twenty-one male Sprague-Dawley rats (seven per group), with body weight of 385-485 g, were categorized into three groups and subjected to different recovery times, each with three repetitive loading cycles at skin tissues above of right trochanter area. The first, second, and third groups were subjected to short (3 minutes), moderate (10 minutes), and prolonged (40 minutes) recovery, respectively, while applying fixed loading time and pressure (10 minutes and 50 mmHg, respectively), to provide different degree of recovery and tissue conditions (tissue damage and tissue recovery). Peak RH was measured in the three cycles to determine RH trend (increasing, decreasing, and inconsistent). All rat tissues were evaluated using ultrasound at pre- and post-experiment and rated by two raters to categorize the severity of tissue changes (no, mild, moderate, and severe). The tissue condition was also evaluated using histopathological examination to distinguish between normal and abnormal tissues. Most of the samples with increasing RH trend is related to abnormal tissue (71%); while inconsistent RH trends is more related to normal tissue (82%). There is no relationship between the tissue conditions evaluated under ultrasonographic and histopathological examination. Peak RH trend over repetitive loading may serve as a new feature for determining the tissue condition that leading to pressure ulcer.
    Matched MeSH terms: Rats, Sprague-Dawley
  6. Histopathological changes in placenta and liver of pregnant rats administered with aqueous extract of Dioscorea hispida var. daemona (Roxb) Prain & Burkill
    Muhammad H, Maslan SF, Md Saad WM, Thani NSIA, Ibnu Rasid EN, Mahomoodally MF, et al.
    Food Chem Toxicol, 2019 Sep;131:110538.
    PMID: 31152790 DOI: 10.1016/j.fct.2019.05.046
    Dioscorea hispida var. daemona (Roxb) Prain & Burkill (DH), also known a tropical yam or intoxicating yam is a bitter wild tuber which is consumed as a staple food and traditionally used as a remedy in Malaysia. However, DH is also notorious for its intoxicating effects and there is currently a dearth of study of possible effects of DH on liver and placental tissues and hence its safe consumption warrants in-depth investigation. This study was therefore designed to investigate into the effect of DH on liver and placenta of pregnant rat via histopathological examination. Thirty pregnant Sprague-Dawley rats were randomly divided into five groups consisting of a control (distilled water) and four DH aqueous extract groups (250, 500, 1000 and 2000 mg/kg body weight). The extracts were administered via oral gavage daily throughout the study and animals were sacrificed on day 21. Paraffin-embedded, hematoxylin and eosin stained sections of placenta and liver were examined. Significant changes (p 
    Matched MeSH terms: Rats, Sprague-Dawley
  7. Fulltext Exposure to High-Fat Style Diet Induced Renal and Liver Structural Changes, Lipid Accumulation and Inflammation in Intact and Ovariectomized Female Rats
    Sucedaram Y, Johns EJ, Husain R, Abdul Sattar M, H Abdulla M, Nelli G, et al.
    J Inflamm Res, 2021;14:689-710.
    PMID: 33716510 DOI: 10.2147/JIR.S299083
    Purpose: We hypothesized that low estrogen levels aggravate obesity-related complications. Diet-induced obesity can cause distinct pathologies, including impaired glucose tolerance, inflammation, and organ injury that leads to fatty liver and chronic kidney diseases. To test this hypothesis, ovariectomized (OVX) rats were fed a high-fat style diet (HFSD), and we examined structural changes and inflammatory response in the kidney and liver.

    Methods: Sprague-Dawley female rats were ovariectomized or sham-operated and divided into four groups: sham-operated rats fed a normal diet (ND); ovariectomized rats fed a normal diet (OVX-ND); sham-operated rats fed a HFSD; ovariectomized rats fed a high-fat style diet (OVX-HFSD). Mean blood pressure and fasting blood glucose were measured on weeks 0 and 10. The rats were sacrificed 10 weeks after initiation of ND or HFSD, the kidney and liver were harvested for histological, immunohistochemical and immunofluorescence studies.

    Results: HFSD-fed rats presented a significantly greater adiposity index compared to their ND counterparts. Liver index, fasting blood glucose and mean blood pressure was increased in OVX-HFSD rats compared to HFSD rats at study terminal. Histological and morphometric studies showed focal interstitial mononuclear cell infiltration in the kidney of HFSD rats with mesangial expansion being greater in the OVX-HFSD rats. Both HFSD fed groups showed increased expressions of renal inflammatory markers, namely TNF-alpha, IL-6 and MCP-1, and infiltrating M1 macrophages with some influence of ovarian hormonal status. HFSD-feeding also caused hepatocellular steatosis which was aggravated in ovariectomized rats fed the same diet. Furthermore, hepatocellular ballooning was observed only in the OVX-HFSD rats. Similarly, HFSD-fed rats showed increased expressions of the inflammatory markers and M1 macrophage infiltration in the liver; however, only IL-6 expression was magnified in the OVX-HFSD.

    Conclusion: Our data suggest that some of the structural changes and inflammatory response in the kidney and liver of rats fed a HFSD are exacerbated by ovariectomy.

    Matched MeSH terms: Rats, Sprague-Dawley
  8. Fulltext Pharmacokinetics and Metabolism of Liposome-Encapsulated 2,4,6-Trihydroxygeranylacetophenone in Rats Using High-Resolution Orbitrap Liquid Chromatography Mass Spectrometry
    Alkhateeb Y, Jarrar QB, Abas F, Rukayadi Y, Tham CL, Hay YK, et al.
    Molecules, 2020 Jul 06;25(13).
    PMID: 32640512 DOI: 10.3390/molecules25133069
    2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is a bioactive compound that shows excellent anti-inflammatory properties. However, its pharmacokinetics and metabolism have yet to be evaluated. In this study, a sensitive LC-HRMS method was developed and validated to quantify tHGA in rat plasma. The method showed good linearity (0.5-80 ng/mL). The accuracy and precision were within 10%. Pharmacokinetic investigations were performed on three groups of six rats. The first two groups were given oral administrations of unformulated and liposome-encapsulated tHGA, respectively, while the third group received intraperitoneal administration of liposome-encapsulated tHGA. The maximum concentration (Cmax), the time required to reach Cmax (tmax), elimination half-life (t1/2) and area under curve (AUC0-24) values for intraperitoneal administration were 54.6 ng/mL, 1.5 h, 6.7 h, and 193.9 ng/mL·h, respectively. For the oral administration of unformulated and formulated tHGA, Cmax values were 5.4 and 14.5 ng/mL, tmax values were 0.25 h for both, t1/2 values were 6.9 and 6.6 h, and AUC0-24 values were 17.6 and 40.7 ng/mL·h, respectively. The liposomal formulation improved the relative oral bioavailability of tHGA from 9.1% to 21.0% which was a 2.3-fold increment. Further, a total of 12 metabolites were detected and structurally characterized. The metabolites were mainly products of oxidation and glucuronide conjugation.
    Matched MeSH terms: Rats, Sprague-Dawley
  9. Synergistic effect of quercetin and quinic acid by alleviating structural degeneration in the liver, kidney and pancreas tissues of STZ-induced diabetic rats: a mechanistic study
    Arya A, Al-Obaidi MM, Shahid N, Bin Noordin MI, Looi CY, Wong WF, et al.
    Food Chem Toxicol, 2014 Sep;71:183-96.
    PMID: 24953551 DOI: 10.1016/j.fct.2014.06.010
    The aim of this study was to investigate the synergistic effects of quercetin (QE) and quinic acid (QA) on a STZ-induced diabetic rat model to determine their potential role in alleviating diabetes and its associated complications. In our study design, diabetic rats were treated with single and combined doses of QE and QA for 45days to analyse their effects on liver, kidney and pancreas tissues. The study result showed that QE and QA treated groups down-regulated hyperglycaemia and oxidative stress by up-regulating insulin and C-peptide levels. Moreover, histological observations of the liver, kidney and pancreas of diabetic rats treated with single and combined doses of QE and QA showed a significant improvement in the structural degeneration. Interestingly, the combination dose of QE and QA (50 mg/kg) exhibited maximum inhibition of the pro-apoptotic protein Bax expression and demonstrate enhancement of the anti-apoptotic protein Bcl-2 expression in the kidney tissues, suggesting a protective role in the kidneys of diabetic rats. Taken together, these results indicates the synergistic effects of QE and QA in ameliorating hyperglycaemia, hyperlipidemia and insulin resistance in diabetic rats and therefore, open a new window of research on the combinatorial therapy of flavonoids.
    Matched MeSH terms: Rats, Sprague-Dawley
  10. Total isoflavones from soybean and tempeh reversed scopolamine-induced amnesia, improved cholinergic activities and reduced neuroinflammation in brain
    Ahmad A, Ramasamy K, Jaafar SM, Majeed AB, Mani V
    Food Chem Toxicol, 2014 Mar;65:120-8.
    PMID: 24373829 DOI: 10.1016/j.fct.2013.12.025
    The present study was undertaken to compare the neuroprotective effects between total isoflavones from soybean and tempeh against scopolamine-induced cognitive dysfunction. Total isoflavones (10, 20 and 40mg/kg) from soybean (SI) and tempeh (TI) were administered orally to different groups of rats (n=6) for 15days. Piracetam (400mg/kg, p.o.) was used as a standard drug while scopolamine (1mg/kg, i.p.) was used to induce amnesia in the animals. Radial arm and elevated plus mazes served as exteroceptive behavioural models to measure memory. Brain cholinergic activities (acetylcholine and acetylcholinesterase) and neuroinflammatory activities (COX-1, COX-2, IL-1β and IL10) were also assessed. Treatment with SI and TI significantly reversed the scopolamine effect and improved memory with TI group at 40mg/kg, p.o. exhibiting the best improvement (p<0.001) in rats. The TI (10, 20 and 40mg/kg, p.o.) significantly increased (p<0.001) acetylcholine and reduced acetylcholinesterase levels. Meanwhile, only a high dose (40mg/kg, p.o.) of SI showed significant improvement (p<0.05) in the cholinergic activities. Neuroinflammation study also showed that TI (40mg/kg, p.o.) was able to reduce inflammation better than SI. The TI ameliorates scopolamine-induced memory in rats through the cholinergic neuronal pathway and by prevention of neuroinflammation.
    Matched MeSH terms: Rats, Sprague-Dawley
  11. Analysis of urinary andrographolides and antioxidant status after oral administration of Andrographis paniculata leaf extract in rats
    Akowuah GA, Zhari I, Mariam A
    Food Chem Toxicol, 2008 Dec;46(12):3616-20.
    PMID: 18824206 DOI: 10.1016/j.fct.2008.09.008
    A simple high-performance liquid chromatography (HPLC) method was developed to determine the content of andrographolide (AP) and 14-deoxy-11,12-dideoxyandrographolide (DIAP) in a pooled urine of rat obtained within 24h after an oral dose of Andrographis paniculata leaf extract at 1g/kg body weight. Cumulative urinary excretion of AP and DIAP in 24h after oral administration of the extract was 0.88% and 1.61% of oral dose administered, respectively. The extract showed significant reduction (p<0.05) of MDA levels and elevation of total antioxidant status in rat urine samples collected in 24 after oral administration.
    Matched MeSH terms: Rats, Sprague-Dawley
  12. Toxicology study of vanillin on rats via oral and intra-peritoneal administration
    Ho K, Yazan LS, Ismail N, Ismail M
    Food Chem Toxicol, 2011 Jan;49(1):25-30.
    PMID: 20807560 DOI: 10.1016/j.fct.2010.08.023
    Vanillin is useful as anti-sickle cell anemia, anti-mutagen and anti-bacteria agent. However, vanillin must be administered at high concentration and cannot be oxidized by the upper gastrointestinal track of patients to be medically effective. In this study, we assessed the toxic effect of vanillin when administered in an un-oxidized form at high concentrations (150 and 300 mg/kg) via oral and intra-peritoneal injection. It was found that 300 mg/kg vanillin injection caused the rats to be unconscious without exerting any toxic effect on blood cells, kidney and liver. Besides, it showed blood protective property. Further analysis with GenomeLab GeXP genetic system on brain tissues showed that the expression of most xenobiotic metabolism, cell progression, tumor suppressor, DNA damage and inflammation genes were maintained at normal level. However, the expression of a few xenobiotic metabolism, cell cycle arrest and apoptosis genes were up-regulated by 5% ethanol injection. Nevertheless, when 5% ethanol was injected with the presence of vanillin, the expression was back to normal level. It is postulated that vanillin might have neuro-protective property. In conclusion, vanillin is not toxic at high concentration in both oral and intra-peritoneal injection and could provide blood and brain protective properties.
    Matched MeSH terms: Rats, Sprague-Dawley
  13. Antioxidant, anti-inflammatory and synergistic anti-hyperglycemic effects of Malaysian propolis and metformin in streptozotocin-induced diabetic rats
    Nna VU, Abu Bakar AB, Md Lazin MRML, Mohamed M
    Food Chem Toxicol, 2018 Oct;120:305-320.
    PMID: 30026088 DOI: 10.1016/j.fct.2018.07.028
    Diabetes mellitus is characterized by hyperglycemia which causes oxidative stress. Propolis has been reported to have antihyperglycemic and antioxidant potentials. The present study therefore examined the anti-hyperglycemic, antioxidant and anti-inflammatory activities of Malaysian propolis (MP) using streptozotocin-induced diabetic rats. Ethanol extract of MP showed in vitro antioxidant (DPPH, FRAP and H2O2 radical scavenging) and α-glucosidase inhibition activities. Male Sprague Dawley rats were either treated with distilled water (normal control and diabetic control), MP (300 mg/kg b. w.), metformin (Met) (300 mg/kg b. w.) or both. After four weeks, fasting blood glucose decreased, while body weight change and serum insulin level increased significantly in MP, Met and MP + Met treated diabetic groups compared to diabetic control (DC) group. Furthermore, pancreatic antioxidant enzymes, total antioxidant capacity, interleukin (IL)-10 and proliferating cell nuclear antigen increased, while malondialdehyde, nuclear factor-kappa B (p65), tumor necrosis factor alpha, IL-1β and cleaved caspase-3 decreased significantly in the treated diabetic groups compared to DC group. Histopathology of the pancreas showed increased islet area and number of beta cells in the treated groups, compared to DC group, with D + MP + Met group comparable to normal control. We conclude that MP has anti-hyperglycemic, antioxidant, anti-inflammatory and antiapoptotic potentials, and exhibits synergistic effect with metformin.
    Matched MeSH terms: Rats, Sprague-Dawley
  14. Fulltext Hepatoprotective and antioxidant activities of Dicranopteris linearis leaf extract against paracetamol-induced liver intoxication in rats
    Zakaria ZA, Kamisan FH, Kek TL, Salleh MZ
    Pharm Biol, 2020 Dec;58(1):478-489.
    PMID: 32476526 DOI: 10.1080/13880209.2020.1764058
    Context:Dicranopteris linearis L. (Gleicheniaceae) leaves have been reported to exert hepatoprotective activity.Objective: The hepatoprotective and antioxidant effects of ethyl acetate partition of D. linearis (EADL) are investigated.Materials and methods: EADL was subjected to antioxidant and anti-inflammatory studies, and phytochemical analyses. In vivo study involved six groups (n = 6) of overnight fasted Sprague Dawley rats. The test solutions [10% DMSO (normal), 10% DMSO (negative), 200 mg/kg silymarin (positive) or EADL (50, 250 or 500 mg/kg)] were administered orally once daily for 7 consecutive days followed by oral vehicle (only for normal) or hepatotoxic induction using 3 g/kg paracetamol (PCM).Results: EADL exerted ≈ 90% radical scavenging effects based on the DPPH and superoxide anion radical scavenging assays, high antioxidant capacity in the oxygen radical absorbance capacity assay (≈ 555,000 units), high total phenolic content (≈ 350 mg GAE/100 g extract) (p 
    Matched MeSH terms: Rats, Sprague-Dawley
  15. Extracellular calcium modulates insulin's action on enzymes controlling cyclic AMP metabolism in intact hepatocytes
    Irvine F, Wallace AV, Sarawak SR, Houslay MD
    Biochem. J., 1993 Jul 01;293 ( Pt 1):249-53.
    PMID: 8392336
    Absence of physiological concentrations of extracellular Ca2+ in the Krebs-Henseleit incubation buffer did not affect the ability of 10 nM glucagon (< 5%) to increase hepatocyte intracellular cyclic AMP concentrations, but severely ablated (by approximately 70%) the ability of 10 nM insulin to decrease these elevated concentrations. Cyclic AMP metabolism is determined by production by adenylate cyclase and degradation by cyclic AMP phosphodiesterase (PDE). In the absence of added extracellular Ca2+ (2.5 mM), insulin's ability to activate PDE activity was selectively compromised, showing a failure of insulin to activate two of the three insulin-stimulated activities, namely the 'dense-vesicle' and peripheral plasma-membrane (PPM) PDEs. In the absence of added Ca2+, insulin's ability to inhibit adenylate cyclase activity in intact hepatocytes was decreased dramatically. Vasopressin and adrenaline (+ propranolol) failed to elicit the activation of either the 'dense-vesicle' or the PPM-PDEs. The presence of physiological concentrations of extracellular Ca2+ in the incubation medium is shown to be important for the appropriate generation of insulin's actions on cyclic AMP metabolism.
    Matched MeSH terms: Rats, Sprague-Dawley
  16. The effects of chronic mitragynine (Kratom) exposure on the EEG in rats
    Suhaimi FW, Hassan Z, Mansor SM, Müller CP
    Neurosci Lett, 2021 02 06;745:135632.
    PMID: 33444671 DOI: 10.1016/j.neulet.2021.135632
    Mitragynine is the main alkaloid isolated from the leaves of Mitragyna speciosa Korth (Kratom). Kratom has been widely used to relieve pain and opioid withdrawal symptoms in humans but may also cause memory deficits. Here we investigated the changes in brain electroencephalogram (EEG) activity after acute and chronic exposure to mitragynine in freely moving rats. Vehicle, morphine (5 mg/kg) or mitragynine (1, 5 and 10 mg/kg) were administered for 28 days, and EEG activity was repeatedly recorded from the frontal cortex, neocortex and hippocampus. Repeated exposure to mitragynine increased delta, but decreased alpha powers in both cortical regions. It further decreased delta power in the hippocampus. These findings suggest that acute and chronic mitragynine can have profound effects on EEG activity, which may underlie effects on behavioral activity and cognition, particularly learning and memory function.
    Matched MeSH terms: Rats, Sprague-Dawley
  17. Effects of EBN on embryo implantation, plasma concentrations of reproductive hormones, and uterine expressions of genes of PCNA, steroids, growth factors and their receptors in rats
    Albishtue AA, Yimer N, Zakaria MZA, Haron AW, Babji AS, Abubakar AA, et al.
    Theriogenology, 2019 Mar 01;126:310-319.
    PMID: 30605790 DOI: 10.1016/j.theriogenology.2018.12.026
    This study was conducted to determine the effect of edible bird's nest (EBN) supplement on uterine function and embryo-implantation rate. A total of 24 adult female rats, divided equally into four groups, were treated with different doses of EBN for 8 weeks. In the last week of treatment, intact fertile male rats were introduced into each group (three per group) for overnight for mating. On day 7 post-mating (post-implantation), blood samples were collected from the hearts of anaesthetised rats that were later sacrificed. The uteri were removed for assessment of embryo implantation rate, histological and electron microscopic examination, and immunohistochemical analyses. Results showed that as the concentration of EBN supplemented increased, the pregnancy and embryo implantation rates were also increased in the treated groups; significantly at G3 and G4. Although histological evaluation did not show much difference among the groups, scanning electron microscopic examination showed enhanced development of elongated microvilli and pinopods in G4. Results also revealed up-regulated expressions of epidermal growth factor (EGF), EGF receptor (EGFR), vascular endothelial growth factor (VEGF), proliferating cell nulear antigen (PCNA), and progesterone and estrogen receptors (P4R, E2R) in the uteri of treated groups. Moreover, plasma E2, P4, growth hormone (GH) and prolactin (P) levels were higher (p 
    Matched MeSH terms: Rats, Sprague-Dawley
  18. Fulltext Philanthotoxin-343 attenuates retinal and optic nerve injury, and protects visual function in rats with N-methyl-D-aspartate-induced excitotoxicity
    Fazel MF, Abu IF, Mohamad MHN, Agarwal R, Iezhitsa I, Bakar NS, et al.
    PLoS One, 2020;15(7):e0236450.
    PMID: 32706792 DOI: 10.1371/journal.pone.0236450
    Retinal ganglion cell (RGC) loss and optic neuropathy, both hallmarks of glaucoma, have been shown to involve N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity. This study investigated the neuroprotective effects of Philanthotoxin (PhTX)-343 in NMDA-induced retinal injury to alleviate ensuing visual impairments. Sprague-Dawley rats were divided into three; Group I was intravitreally injected with phosphate buffer saline as the control, Group II was injected with NMDA (160 nM) to induce retinal excitotoxic injury, while Group III was injected with PhTX-343 (160 nM) 24 h prior to excitotoxicity induction with NMDA. Rats were subjected to visual behaviour tests seven days post-treatment and subsequently euthanized. Rat retinas and optic nerves were subjected to H&E and toluidine blue staining, respectively. Histological assessments showed that NMDA exposure resulted in significant loss of retinal cell nuclei and thinning of ganglion cell layer (GCL). PhTX-343 pre-treatment prevented NMDA-induced changes where the RGC layer morphology is similar to the control. The numbers of nuclei in the NMDA group were markedly lower compared to the control (p<0.05). PhTX-343 group had significantly higher numbers of nuclei within 100 μm length and 100 μm2 area of GCL (2.9- and 1.7-fold, respectively) compared to NMDA group (p<0.05). PhTX-343 group also displayed lesser optic nerve fibres degeneration compared to NMDA group which showed vacuolation in all sections. In the visual behaviour test, the NMDA group recorded higher total distance travelled, and lower total immobile time and episodes compared to the control and PhTX-343 groups (p<0.05). Object recognition tests showed that the rats in PhTX-343 group could recognize objects better, whereas the same objects were identified as novel by NMDA rats despite multiple exposures (p<0.05). Visual performances in the PhTX-343 group were all comparable with the control (p>0.05). These findings suggested that PhTX-343 inhibit retinal cell loss, optic nerve damage, and visual impairments in NMDA-induced rats.
    Matched MeSH terms: Rats, Sprague-Dawley
  19. Effects of age on feeding response: Focus on the rostral C1 neuron and its glucoregulatory proteins
    Ramlan H, Damanhuri HA
    Exp Gerontol, 2020 01;129:110779.
    PMID: 31705967 DOI: 10.1016/j.exger.2019.110779
    BACKGROUND: Older people are likely to develop anorexia of aging. Rostral C1 (rC1) catecholaminergic neurons in rostral ventrolateral medulla (RVLM) are recently discovered its role in food intake control. It is well established that these neurons regulate cardiovascular function.

    OBJECTIVE: This study aims to determine the effect of age on the function of rostral C1 (rC1) neurons in mediating feeding response.

    METHOD: Male Sprague Dawley rats at 3-months (n = 22) and 24-months (n = 22) old were used and further divided into two subgroups; 1) treatment group with 2-deoxy-d-glucose (2DG) and 2) vehicle group. Feeding hormones such as cholecystokinin (CCK), ghrelin and leptin were analysed using enzyme-linked immunosorbent assay (ELISA). Rat brain was carefully dissected to obtain the brainstem RVLM region. Further analysis was carried out to determine the level of proteins and genes in RVLM that were associated with feeding pathway. Protein expression of tyrosine hydroxylase (TH), phosphorylated TH at Serine40 (pSer40TH), AMP-activated protein kinase (AMPK), phosphorylated AMPK (phospho AMPK) and neuropeptide Y Y5 receptor (NPY5R) were determined by western blot. Expression of TH, AMPK and NPY genes were determined by real-time PCR.

    RESULTS: This study showed that blood glucose level was elevated in young and old rats following 2DG administration. Plasma CCK-8 concentration was higher in the aged rats at basal and increased with 2DG administration in young rats, but the leptin and ghrelin showed no changes. Old rats showed higher TH and lower AMPK mRNA levels. Glucoprivation decreased AMPK mRNA level in young rats and decreased TH mRNA in old rats. Aged rC1 neurons showed higher NPY5R protein level. Following glucoprivation, rC1 neurons produced distinct molecular changes across age in which, in young rats, AMPK phosphorylation level was increased and in old rats, TH phosphorylation level was increased.

    CONCLUSION: These findings suggest that glucose-counterregulatory responses by rC1 neurons at least, contribute to the ability of young and old rats in coping glucoprivation. Age-induced molecular changes within rC1 neurons may attenuate the glucoprivic responses. This situation may explain the impairment of feeding response in the elderly.

    Matched MeSH terms: Rats, Sprague-Dawley
  20. Dermal exposure to the herbicide-paraquat results in genotoxic and cytotoxic damage to germ cells in the male rat
    D'Souza UJ, Narayana K, Zain A, Raju S, Nizam HM, Noriah O
    Folia Morphol (Warsz), 2006 Feb;65(1):6-10.
    PMID: 16783728
    The effects of exposure to low doses of paraquat, a herbicide, via the dermal route were studied on the spermatozoa of Sprague-Dawley rats. Paraquat (1, 1'-dimethyl-4, 4'-bipyridinium dichloride) was administered once a day for five days, at intervals of 24 h at 0, 6, 15 and 30 mg/kg, and the rats were sacrificed on days 7, 14, 28, and 42 after the last exposure. The sperm suspensions were obtained by mincing the caudae epididymes and ductus deferens for the purpose of performing a sperm morphology test, sperm count and analysis of sperm mortality and sperm motility, as per the standard procedures. The sperm count was decreased (p < 0.05) only on days 7 and 14 but sperm abnormalities increased on all days (p < 0.05). Sperm mortality increased at higher dose-levels (p < 0.05) except on day 42, and motility was affected by 30 mg/kg only on day 42. In conclusion, paraquat is a genotoxic and cytotoxic agent to germ cells in the male rat.
    Matched MeSH terms: Rats, Sprague-Dawley
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