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Fulltext The protective effect of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes

Mohamed J, Shing SW, Idris MH, Budin SB, Zainalabidin S

Clinics (Sao Paulo), 2013 Oct;68(10):1358-63.
PMID: 24212844 DOI: 10.6061/clinics/2013(10)11

OBJECTIVES: The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell (RBC) membrane oxidative stress in rats with streptozotocin-induced diabetes.
METHODS: Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each): control group (N), roselle-treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-feeding with aqueous extracts of roselle (100 mg/kg body weight) for 28 days.
RESULTS: The results demonstrated that the malondialdehyde levels of the red blood cell membranes in the diabetic group were significantly higher than the levels in the roselle-treated control and roselle-treated diabetic groups. The protein carbonyl level was significantly higher in the roselle-treated diabetic group than in the roselle-treated control group but lower than that in the diabetic group. A significant increase in the red blood cell membrane superoxide dismutase enzyme was found in roselle-treated diabetic rats compared with roselle-treated control rats and diabetic rats. The total protein level of the red blood cell membrane, osmotic fragility, and red blood cell morphology were maintained.
CONCLUSION: The present study demonstrates that aqueous extracts of roselle possess a protective effect against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. These data suggest that roselle can be used as a natural antioxidative supplement in the prevention of oxidative damage in diabetic patients.

Matched MeSH terms: Rats, Sprague-Dawley; Rats
Fulltext Impact of prolonged nicotine administration on myocardial function and susceptibility to ischaemia-reperfusion injury in rats

Ramalingam A, Mohd Fauzi N, Budin SB, Zainalabidin S

Basic Clin Pharmacol Toxicol, 2021 Feb;128(2):322-333.
PMID: 32991780 DOI: 10.1111/bcpt.13500

This study investigated the impact of prolonged nicotine administration on myocardial susceptibility to ischaemia-reperfusion (I/R) injury in a rat model and determined whether nicotine affects mitochondrial reactive oxygen species (ROS) production and permeability transition in rat hearts. Sprague-Dawley rats were administered 0.6 or 1.2 mg/kg nicotine for 28 days, and their hearts were isolated at end-point for assessment of myocardial susceptibility to I/R injury ex vivo. Rat heart mitochondria were also isolated from a subset of rats for analysis of mitochondrial ROS production and permeability transition. Compared to the vehicle controls, rat hearts isolated from nicotine-administered rats exhibited poorer left ventricular function that worsened over the course of I/R. Coronary flow rate was also severely impaired in the nicotine groups at baseline and this worsened after I/R. Nicotine administration significantly increased mitochondrial ROS production and permeability transition relative to the vehicle controls. Interestingly, pre-incubation of isolated mitochondria with ROS scavengers (superoxide dismutase and mitoTEMPO) significantly abolished nicotine-induced increase in mitochondria permeability transition in isolated rat heart mitochondria. Overall, our data showed that prolonged nicotine administration enhances myocardial susceptibility to I/R injury in rats and this is associated with mitochondrial ROS-driven increase in mitochondrial permeability transition.

Matched MeSH terms: Rats, Sprague-Dawley; Rats
Fulltext The pyramid counteracts chronic prenatal restraint-stress effects on the milestones, anthropometry, and body, brain and adrenal gland weights of pups in rats

George, Mitchel Constance, Murthy, Krishna Dilip, Zainal Arifin Mustapha

Borneo Journal of Medical Sciences, 2018;12(1):49-56.
MyJurnal

Prenatal exposure to chronic stress during critical periods of foetal development produces depression, attention and learning deficits, hormonal imbalances and affects the brain. The effect of prenatal restraint-stress on the postnatal developmental milestones, anthropometric measurements, and the body, brain and adrenal gland weights of the pups were examined and compared with the unrestrained control and the restrained group under the pyramid at postnatal day 10 and 21. Pregnant rats were restrained (9h/day) from gestation day 7 until parturition. Results showed significant delay in the milestones by one day in the restraint control (RC) compared to the unrestrained normal control (NC), while pups of the restrained pyramid (RP) group did not show the delay. Significant decreases in the anthropometric measurements, body and brain weights in RC group were observed at both postnatal days, while the RP group results matched with the NC group. Significant increase in the adrenal weights was found in the RC group compared to NC group and not the RP group. Results suggest prenatal restraint-stress definitely hampers the developmental milestones, anthropometric measurements, and body and brain weights of the young offspring. Results suggest, pyramid environment counteracts and protects the deleterious effects of chronic prenatal stress.

Matched MeSH terms: Rats
Fulltext Antihyperglycemic activity of oil palm elaeis guineensis fruit extract on streptozotocin-induced diabetic rats

Faez Sharif, Muhajir Hamid, Amin Ismail, Zainah Adam

Jurnal Sains Kesihatan Malaysia, 2015;13(2):37-43.
MyJurnal

Hypoglycaemic and antihyperglycemic activity of oil palm Elaeis guineensis fruit extract on normal and Streptozotocininduced
diabetic rats was studied. The oil palm fruit extract (OPF) were administered orally at different concentrations (100,
200 and 500 mg kg-1 b.w.) in fasting and post-prandial rats. Hypoglycaemia was not observed in the group of normal rats
treated with OPF. In fasting rats, OPF (500 mg kg-1 b.w.) has caused the blood glucose level (BGL) to reduce significantly.
For post-prandial diabetic rats, the antihyperglycemic activity was observed after OPF treatment at concentrations 200
and 500 mg kg-1. Chronic OPF treatments (for 28 days) had increased the diabetic rat’s body weight and reduced BGL as
well as improved plasma insulin secretion. The result of this study suggests E. guineensis palm fruit extract show evidence
of antihyperglycemic properties from the reduction of the BGL in diabetic rats.

Matched MeSH terms: Rats
Fulltext Tualang honey exerts antioxidant and antidepressant-like effects in stress-exposed rats

Khairunnuur Fairuz Azman, Rahimah Zakaria, Che Badariah Abdul Aziz, Zahiruddin Othman

Malaysian Journal of Applied Sciences, 2019;4(1):15-25.
MyJurnal

Recent evidence has exhibited dietary influence on the manifestation of depressive-like behaviour induced by stressor tasks. The present study examined the effects of Tualang honey supplement administered with the goal of preventing or attenuating the occurrence of depressive-like behaviour in male rats subjected to noise stress. Forty-eight adult male rats were randomly divided into the following groups: i) nonstressed with placebo, ii) nonstressed with honey, iii) stressed with placebo, and iv) stressed with honey. Tualang honey (200 mg/kg body weight) was administered for 28 days. Stressed rats were subjected to loud noise 100 dB(A) 4 hours daily for 14 days. Forced swimming test was performed to evaluate depressive-like behaviour. Stressed control rats displayed significant increase in depressive-like behaviour, serum adrenocorticotropic hormone (ACTH), corticosterone, and brain oxidative stress markers levels, with significant decrease in antioxidant enzymes activities and total antioxidant status. Honey supplementation successfully counteracted the stress effects whereby the honey treated rats exhibited significant decrease in depressive-like behaviour and levels of ACTH, corticosterone, and oxidative stress markers, with significant increase in antioxidant enzymes activities and total antioxidant status. In conclusion, Tualang honey mediated antidepressant-like effects in stressed rats, possibly acting via restoration of hypothalamic-pituitary-adrenal axis through its antioxidant properties.

Matched MeSH terms: Rats
Bone regeneration performance of surface-treated porous titanium

Amin Yavari S, van der Stok J, Chai YC, Wauthle R, Tahmasebi Birgani Z, Habibovic P, et al.

Biomaterials, 2014 Aug;35(24):6172-81.
PMID: 24811260 DOI: 10.1016/j.biomaterials.2014.04.054

The large surface area of highly porous titanium structures produced by additive manufacturing can be modified using biofunctionalizing surface treatments to improve the bone regeneration performance of these otherwise bioinert biomaterials. In this longitudinal study, we applied and compared three types of biofunctionalizing surface treatments, namely acid-alkali (AcAl), alkali-acid-heat treatment (AlAcH), and anodizing-heat treatment (AnH). The effects of treatments on apatite forming ability, cell attachment, cell proliferation, osteogenic gene expression, bone regeneration, biomechanical stability, and bone-biomaterial contact were evaluated using apatite forming ability test, cell culture assays, and animal experiments. It was found that AcAl and AnH work through completely different routes. While AcAl improved the apatite forming ability of as-manufactured (AsM) specimens, it did not have any positive effect on cell attachment, cell proliferation, and osteogenic gene expression. In contrast, AnH did not improve the apatite forming ability of AsM specimens but showed significantly better cell attachment, cell proliferation, and expression of osteogenic markers. The performance of AlAcH in terms of apatite forming ability and cell response was in between both extremes of AnH and AsM. AcAl resulted in significantly larger volumes of newly formed bone within the pores of the scaffold as compared to AnH. Interestingly, larger volumes of regenerated bone did not translate into improved biomechanical stability as AnH exhibited significantly better biomechanical stability as compared to AcAl suggesting that the beneficial effects of cell-nanotopography modulations somehow surpassed the benefits of improved apatite forming ability. In conclusion, the applied surface treatments have considerable effects on apatite forming ability, cell attachment, cell proliferation, and bone ingrowth of the studied biomaterials. The relationship between these properties and the bone-implant biomechanics is, however, not trivial.

Matched MeSH terms: Rats, Wistar
Fulltext Palm vitamin E reduces locomotor dysfunction and morphological changes induced by spinal cord injury and protects against oxidative damage

Zadeh-Ardabili PM, Rad SK, Rad SK, Khazaài H, Sanusi J, Zadeh MH

Sci Rep, 2017 10 30;7(1):14365.
PMID: 29085045 DOI: 10.1038/s41598-017-14765-3

Spinal cord injury (SCI) occurs following different types of crushes. External and internal outcomes of SCI are including paralysis, cavity, and cyst formation. Effects of dietary derived antioxidants, such as palm vitamin E on central nervous system (CNS) encourage researchers to focus on the potential therapeutic benefits of antioxidant supplements. In the present study, experiments were carried out to evaluate the neuro-protective effect of the palm vitamin E on locomotor function and morphological damages induced SCI. Seventy-two male rats (Sprague-Dawley) were randomly divided into four groups: sham (laminectomy); control (supplemented with the palm vitamin E at a dose of 100 mg/kg/day); untreated-SCI (partial crush, 30-33% for 20 sec); treated-SCI (partial crush, 30-33% for 20 sec supplemented with the palm vitamin E at a dose of 100 mg/kg/day). The treatment with the palm vitamin E significantly improved the hind limb locomotor function, reduced the histopathological changes and the morphological damage in the spinal cord. Also, the palm vitamin E indicated a statistically significant decrease in the oxidative damage indicators, malondialdehyde (MDA) level and glutathione peroxidase (GPx) activity in the treated-SCI compared to the untreated-SCI.

Matched MeSH terms: Rats, Sprague-Dawley; Rats
Histological and histometrical study of the protective role of α-tocopherol against sodium arsenite toxicity in rat ovaries

Dezfouli MG, Eissazadeh S, Zade SM

Microsc Microanal, 2014 Aug;20(4):1167-79.
PMID: 24735566 DOI: 10.1017/S1431927614000701

This study examines histometrical changes induced by sodium arsenite (SA), as an environmental pollutant, and investigates the protective effect of α-tocopherol on ovaries of SA-treated rats during the prenatal stage until sexual maturity. Rats were classified into groups: control, SA (8 ppm/day), α-tocopherol (100 ppm/day), and SA+α-tocopherol. Treatment was performed from pregnancy until maturation when the rats and ovaries were weighed. The Cavalieri method was used to estimate volume of the ovaries, cortex, medulla, and corpus luteum. The mean diameter of oocytes, granulosa cells, and nuclei were measured and volume was estimated using the Nucleator method. The number of oocytes and thickness of the zona pellucida (ZP) were determined using an optical dissector and orthogonal intercept method, respectively. SA reduced the body and ovary weight, the number of secondary, antral and Graafian oocytes, volume of the ovaries, cortex, medulla and corpus luteum, mean diameter and volume of oocytes in primordial and primary follicles, mean diameter and volume of oocyte nuclei in all types of follicles, and mean thickness of the ZP in secondary and antral follicles. Also, the mean diameter and volume of granulosa cells and their nuclei in antral and Graafian follicles decreased significantly. Vacuolization and vascular congestion in the corpus luteum and an increase in the number of atretic oocytes were seen in the SA group. Most of these parameters were unchanged from the control level in the SA+α-tocopherol group. It was concluded that α-tocopherol supplementation reduced the toxic effects of SA exposure on ovarian tissue in rats.

Matched MeSH terms: Rats
Fulltext Edible Bird's Nest Prevents High Fat Diet-Induced Insulin Resistance in Rats

Yida Z, Imam MU, Ismail M, Ooi DJ, Sarega N, Azmi NH, et al.

J Diabetes Res, 2015;2015:760535.
PMID: 26273674 DOI: 10.1155/2015/760535

Edible bird's nest (EBN) is used traditionally in many parts of Asia to improve wellbeing, but there are limited studies on its efficacy. We explored the potential use of EBN for prevention of high fat diet- (HFD-) induced insulin resistance in rats. HFD was given to rats with or without simvastatin or EBN for 12 weeks. During the intervention period, weight measurements were recorded weekly. Blood samples were collected at the end of the intervention and oral glucose tolerance test conducted, after which the rats were sacrificed and their liver and adipose tissues collected for further studies. Serum adiponectin, leptin, F2-isoprostane, insulin, and lipid profile were estimated, and homeostatic model assessment of insulin resistance computed. Effects of the different interventions on transcriptional regulation of insulin signaling genes were also evaluated. The results showed that HFD worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. Additionally, simvastatin was able to prevent hypercholesterolemia but promoted insulin resistance similar to HFD. EBN, on the other hand, prevented the worsening of metabolic indices and transcriptional changes in insulin signaling genes due to HFD. The results suggest that EBN may be used as functional food to prevent insulin resistance.

Matched MeSH terms: Rats, Sprague-Dawley; Rats
Anti-angiogenic quassinoid-rich fraction from Eurycoma longifolia modulates endothelial cell function

Al-Salahi OS, Kit-Lam C, Majid AM, Al-Suede FS, Mohammed Saghir SA, Abdullah WZ, et al.

Microvasc Res, 2013 Nov;90:30-9.
PMID: 23899415 DOI: 10.1016/j.mvr.2013.07.007

Targeting angiogenesis could be an excellent strategy to combat angiogenesis-dependent pathophysiological conditions such as cancer, rheumatoid arthritis, obesity, systemic lupus erythematosus, psoriasis, proliferative retinopathy and atherosclerosis. Recently a number of clinical investigations are being undertaken to assess the potential therapeutic application of various anti-angiogenic agents. Many of these angiogenesis inhibitors are directed against the functions of endothelial cells, which are considered as the building blocks of blood vessels. Similarly, roots of a traditional medicinal plant, Eurycoma longifolia, can be used as an alternative treatment to prevent and treat the angiogenesis-related diseases. In the present study, antiangiogenic potential of partially purified quassinoid-rich fraction (TAF273) of E. longifolia root extract was evaluated using ex vivo and in vivo angiogenesis models and the anti-angiogenic efficacy of TAF273 was investigated in human umbilical vein endothelial cells (HUVEC). TAF273 caused significant suppression in sprouting of microvessels in rat aorta with IC50 11.5μg/ml. TAF273 (50μg/ml) showed remarkable inhibition (63.13%) of neovascularization in chorioallantoic membrane of chick embryo. Tumor histology also revealed marked reduction in extent of vascularization. In vitro, TAF273 significantly inhibited the major angiogenesis steps such as proliferation, migration and differentiation of HUVECs. Phytochemical analysis revealed high content of quassinoids in TAF273. Specially, HPLC characterization showed that TAF273 is enriched with eurycomanone, 13α(21)-epoxyeurycomanone and eurycomanol. These results demonstrated that the antiangiogenic activity of TAF273 may be due to its inhibitory effect on endothelial cell proliferation, differentiation and migration which could be attributed to the high content of quassinoids in E. longifolia.

Matched MeSH terms: Rats, Sprague-Dawley; Rats
Fulltext Gelam honey scavenges peroxynitrite during the immune response

Kassim M, Mansor M, Suhaimi A, Ong G, Yusoff KM

Int J Mol Sci, 2012;13(9):12113-29.
PMID: 23109904 DOI: 10.3390/ijms130912113

Monocytes and macrophages are part of the first-line defense against bacterial, fungal, and viral infections during host immune responses; they express high levels of proinflammatory cytokines and cytotoxic molecules, including nitric oxide, reactive oxygen species, and their reaction product peroxynitrite. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death. Honey, in addition to its well-known sweetening properties, is a natural antioxidant that has been used since ancient times in traditional medicine. We examined the ability of Gelam honey, derived from the Gelam tree (Melaleuca spp.), to scavenge peroxynitrite during immune responses mounted in the murine macrophage cell line RAW 264.7 when stimulated with lipopolysaccharide/interferon-γ (LPS/IFN-γ) and in LPS-treated rats. Gelam honey significantly improved the viability of LPS/IFN-γ-treated RAW 264.7 cells and inhibited nitric oxide production-similar to the effects observed with an inhibitor of inducible nitric oxide synthase (1400W). Furthermore, honey, but not 1400W, inhibited peroxynitrite production from the synthetic substrate 3-morpholinosydnonimine (SIN-1) and prevented the peroxynitrite-mediated conversion of dihydrorhodamine 123 to its fluorescent oxidation product rhodamine 123. Honey inhibited peroxynitrite synthesis in LPS-treated rats. Thus, honey may attenuate inflammatory responses that lead to cell damage and death, suggesting its therapeutic uses for several inflammatory disorders.

Matched MeSH terms: Rats, Sprague-Dawley; Rats
The inhibitory effects of Gelam honey and its extracts on nitric oxide and prostaglandin E(2) in inflammatory tissues

Kassim M, Achoui M, Mansor M, Yusoff KM

Fitoterapia, 2010 Dec;81(8):1196-201.
PMID: 20708657 DOI: 10.1016/j.fitote.2010.07.024

We investigated the effects of honey and its methanol and ethyl acetate extracts on inflammation in animal models. Rats' paws were induced with carrageenan in the non-immune inflammatory and nociceptive model, and lipopolysaccharide (LPS) in the immune inflammatory model. Honey and its extracts were able to inhibit edema and pain in inflammatory tissues as well as showing potent inhibitory activities against NO and PGE(2) in both models. The decrease in edema and pain correlates with the inhibition of NO and PGE(2). Phenolic compounds have been implicated in the inhibitory activities. Honey is potentially useful in the treatment of inflammatory conditions.

Matched MeSH terms: Rats, Sprague-Dawley; Rats
Fulltext The Efficacy of Gelam Honey Dressing towards Excisional Wound Healing

Tan MK, Hasan Adli DS, Tumiran MA, Abdulla MA, Yusoff KM

Evid Based Complement Alternat Med, 2012;2012:805932.
PMID: 22536292 DOI: 10.1155/2012/805932

Honey is one of the oldest substances used in wound management. Efficacy of Gelam honey in wound healing was evaluated in this paper. Sprague-Dawley rats were randomly divided into four groups of 24 rats each (untreated group, saline group, Intrasite Gel group, and Gelam honey group) with 2 cm by 2 cm full thickness, excisional wound created on neck area. Wounds were dressed topically according to groups. Rats were sacrificed on days 1, 5, 10, and 15 of treatments. Wounds were then processed for macroscopic and histological observations. Gelam-honey-dressed wounds healed earlier (day 13) than untreated and saline treated groups, as did wounds treated with Intrasite Gel. Honey-treated wounds exhibited less scab and only thin scar formations. Histological features demonstrated positive effects of Gelam honey on the wounds. This paper showed that Gelam honey dressing on excisional wound accelerated the process of wound healing.

Matched MeSH terms: Rats, Sprague-Dawley; Rats
Fulltext Effect of the combination of gelam honey and ginger on oxidative stress and metabolic profile in streptozotocin-induced diabetic Sprague-Dawley rats

Sani NF, Belani LK, Sin CP, Rahman SN, Das S, Chi TZ, et al.

Biomed Res Int, 2014;2014:160695.
PMID: 24822178 DOI: 10.1155/2014/160695

Diabetic complications occur as a result of increased reactive oxygen species (ROS) due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight). Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight), ginger (60 mg/kg body weight), and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH): oxidized glutathione (GSSG), and malondialdehyde (MDA). The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P < 0.05) SOD and CAT activities as well as MDA level, while GSH level and GSH/GSSG ratio were significantly elevated (P < 0.05) in STZ-induced diabetic rats compared to diabetic control rats.

Matched MeSH terms: Rats, Sprague-Dawley; Rats
Ginger extract (Zingiber officinale) has anti-cancer and anti-inflammatory effects on ethionine-induced hepatoma rats

Habib SH, Makpol S, Abdul Hamid NA, Das S, Ngah WZ, Yusof YA

Clinics (Sao Paulo), 2008 Dec;63(6):807-13.
PMID: 19061005

OBJECTIVE: To evaluate the effect of ginger extract on the expression of NFkappaB and TNF-alpha in liver cancer-induced rats.
METHODS: Male Wistar rats were randomly divided into 5 groups based on diet: i) control (given normal rat chow), ii) olive oil, iii) ginger extract (100mg/kg body weight), iv) choline-deficient diet + 0.1% ethionine to induce liver cancer and v) choline-deficient diet + ginger extract (100mg/kg body weight). Tissue samples obtained at eight weeks were fixed with formalin and embedded in paraffin wax, followed by immunohistochemistry staining for NFkappaB and TNF-alpha.
RESULTS: The expression of NFkappaB was detected in the choline-deficient diet group, with 88.3 +/- 1.83% of samples showing positive staining, while in the choline-deficient diet supplemented with ginger group, the expression of NFkappaB was significantly reduced, to 32.35 +/- 1.34% (p<0.05). In the choline-deficient diet group, 83.3 +/- 4.52% of samples showed positive staining of TNF-alpha, which was significantly reduced to 7.94 +/- 1.32% (p<0.05) when treated with ginger. There was a significant correlation demonstrated between NFkappaB and TNF-alpha in the choline-deficient diet group but not in the choline-deficient diet treated with ginger extract group.
CONCLUSION: In conclusion, ginger extract significantly reduced the elevated expression of NFkappaB and TNF-alpha in rats with liver cancer. Ginger may act as an anti-cancer and anti-inflammatory agent by inactivating NFkappaB through the suppression of the pro-inflammatory TNF-alpha.

Matched MeSH terms: Rats, Wistar; Rats
Changes in blood-brain barrier permeability and ultrastructure, and protein expression in a rat model of cerebral hypoperfusion

Sekaran H, Gan CY, A Latiff A, Harvey TM, Mohd Nazri L, Hanapi NA, et al.

Brain Res Bull, 2019 10;152:63-73.
PMID: 31301381 DOI: 10.1016/j.brainresbull.2019.07.010

Cerebral hypoperfusion involved a reduction in cerebral blood flow, leading to neuronal dysfunction, microglial activation and white matter degeneration. The effects on the blood-brain barrier (BBB) however, have not been well-documented. Here, two-vessel occlusion model was adopted to mimic the condition of cerebral hypoperfusion in Sprague-Dawley rats. The BBB permeability to high and low molecular weight exogenous tracers i.e. Evans blue dye and sodium fluorescein respectively, showed marked extravasation of the Evans blue dye in the frontal cortex, posterior cortex and thalamus-midbrain at day 1 following induction of cerebral hypoperfusion. Transmission electron microscopy revealed brain endothelial cell and astrocyte damages including increased pinocytotic vesicles and formation of membrane invaginations in the endothelial cells, and swelling of the astrocytes' end-feet. Investigation on brain microvessel protein expressions using two-dimensional (2D) gel electrophoresis coupled with LC-MS/MS showed that proteins involved in mitochondrial energy metabolism, transcription regulation, cytoskeleton maintenance and signaling pathways were differently expressed. The expression of aconitate hydratase, heterogeneous nuclear ribonucleoprotein, enoyl Co-A hydratase and beta-synuclein were downregulated, while the opposite observed for calreticulin and enhancer of rudimentary homolog. These findings provide insights into the BBB molecular responses to cerebral hypoperfusion, which may assist development of future therapeutic strategies.

Matched MeSH terms: Rats, Sprague-Dawley; Rats
Fulltext NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy

Rothan HA, Amini E, Faraj FL, Golpich M, Teoh TC, Gholami K, et al.

Sci Rep, 2017 03 30;7:45540.
PMID: 28358047 DOI: 10.1038/srep45540

N-methyl-D-aspartate receptors (NMDAR) play a central role in epileptogensis and NMDAR antagonists have been shown to have antiepileptic effects in animals and humans. Despite significant progress in the development of antiepileptic therapies over the previous 3 decades, a need still exists for novel therapies. We screened an in-house library of small molecules targeting the NMDA receptor. A novel indolyl compound, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, (DDBM) showed the best binding with the NMDA receptor and computational docking data showed that DDBM antagonised the binding sites of the NMDA receptor at lower docking energies compared to other molecules. Using a rat electroconvulsive shock (ECS) model of epilepsy we showed that DDBM decreased seizure duration and improved the histological outcomes. Our data show for the first time that indolyls like DDBM have robust anticonvulsive activity and have the potential to be developed as novel anticonvulsants.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext Antibiofilm activity, compound characterization, and acute toxicity of extract from a novel bacterial species of paenibacillus

Alasil SM, Omar R, Ismail S, Yusof MY

Int J Microbiol, 2014;2014:649420.
PMID: 24790603 DOI: 10.1155/2014/649420

The effectiveness of many antimicrobial agents is currently decreasing; therefore, it is important to search for alternative therapeutics. Our study was carried out to assess the in vitro antibiofilm activity using microtiter plate assay, to characterize the bioactive compounds using Ultra Performance Liquid Chromatography-Diode Array Detection and Liquid Chromatography-Mass Spectrometry and to test the oral acute toxicity on Sprague Dawley rats of extract derived from a novel bacterial species of Paenibacillus strain 139SI. Our results indicate that the crude extract and its three identified compounds exhibit strong antibiofilm activity against a broad range of clinically important pathogens. Three potential compounds were identified including an amino acid antibiotic C8H20N3O4P (MW 253.237), phospholipase A2 inhibitor C21H36O5 (MW 368.512), and an antibacterial agent C14H11N3O2 (MW 253.260). The acute toxicity test indicates that the mortality rate among all rats was low and that the biochemical parameters, hematological profile, and histopathology examination of liver and kidneys showed no significant differences between experimental groups (P > 0.05). Overall, our findings suggest that the extract and its purified compounds derived from novel Paenibacillus sp. are nontoxic exhibiting strong antibiofilm activity against Gram-positive and Gram-negative pathogens that can be useful towards new therapeutic management of biofilm-associated infections.

Matched MeSH terms: Rats, Sprague-Dawley; Rats
Effect of bradykinin and its antagonist on survival time after coronary artery occlusion in rats

Atif Abbas S, Sharma JN, Pauzi A, Yusof M

Gen. Pharmacol., 1999 Sep;33(3):243-7.
PMID: 10480657

The present study was conducted to examine the effect of bradykinin and bradykinin 2 receptor antagonist on survival time in rats with coronary artery ligation for 15 min and continuously. We also evaluated the heart rate and blood pressure responses in the presence and absence of bradykinin and its antagonist. Bradykinin treatment (4 microg and 8 microg/kg IV) significantly (p < 0.05) increased the survival time of rats compared with saline-treated rats with coronary artery ligation for 15 min and continuously. The heart rate and blood pressure responses were significantly (p < 0.001) altered in the presence of coronary artery ligation. Bradykinin antagonist treatment (4 microg/kg IV) abolished the effect of bradykinin and thus reduced the survival time of rats with coronary artery ligation. The mean value of survival time between saline-treated and bradykinin antagonist- plus bradykinin-treated rats did not differ significantly (p > 0.05).

Matched MeSH terms: Rats, Inbred WKY; Rats
Fulltext Antidiabetic properties and mechanism of action of Gynura procumbens water extract in streptozotocin-induced diabetic rats

Hassan Z, Yam MF, Ahmad M, Yusof AP

Molecules, 2010;15(12):9008-23.
PMID: 21150821 DOI: 10.3390/molecules15129008

Gynura procumbens (Lour.) Merr (family Compositae) is cultivated in Southeast Asia, especially Indonesia, Malaysia and Thailand, for medicinal purposes. This study evaluated the in vivo hypoglycemic properties of the water extract of G. procumbens following 14 days of treatment and in vitro in RIN-5F cells. Glucose absorption from the intestines and its glucose uptake in abdominal skeletal muscle were assessed. The antidiabetic effect of water extract of G. procumbens leaves was investigated in streptozotocin-induced diabetic rats. The intraperitoneal glucose tolerance test (IPGTT) was performed in diabetic rats treated with G. procumbens water extract for 14 days. In the IPGTT, blood was collected for insulin and blood glucose measurement. After the IPGTT, the pancreases were collected for immunohistochemical study of β-cells of the islets of Langerhans. The possible antidiabetic mechanisms of G. procumbens were assessed through in vitro RIN-5F cell study, intestinal glucose absorption and glucose uptake by muscle. The results showed that G. procumbens significantly decreased blood glucose levels after 14 days of treatment and improved outcome of the IPGTT. However, G. procumbens did not show a significant effect on insulin level either in the in vivo test or the in vitro RIN-5F cell culture study. G. procumbens also showed minimal effects on β-cells of the islets of Langerhans in the pancreas. However, G. procumbens only significantly increased glucose uptake by muscle tissues. From the findings we can conclude that G. procumbens water extract exerted its hypoglycemic effect by promoting glucose uptake by muscles.

Matched MeSH terms: Rats, Sprague-Dawley; Rats

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