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  1. Khoo LW, Audrey Kow SF, Maulidiani M, Lee MT, Tan CP, Shaari K, et al.
    J Pharm Biomed Anal, 2018 Sep 05;158:438-450.
    PMID: 29957507 DOI: 10.1016/j.jpba.2018.06.038
    The present study sought to identify the key biomarkers and pathways involved in the induction of allergic sensitization to ovalbumin and to elucidate the potential anti-anaphylaxis property of Clinacanthus nutans (Burm. f.) Lindau water leaf extract, a Southeast Asia herb in an in vivo ovalbumin-induced active systemic anaphylaxis model evaluated by 1H-NMR metabolomics. The results revealed that carbohydrate metabolism (glucose, myo-inositol, galactarate) and lipid metabolism (glycerol, choline, sn-glycero-3-phosphocholine) are the key requisites for the induction of anaphylaxis reaction. Sensitized rats treated with 2000 mg/kg bw C. nutans extract before ovalbumin challenge showed a positive correlation with the normal group and was negatively related to the induced group. Further 1H-NMR analysis in complement with Kyoto Encyclopedia of Genes and Genomes (KEGG) reveals the protective effect of C. nutans extract against ovalbumin-induced anaphylaxis through the down-regulation of lipid metabolism (choline, sn-glycero-3-phosphocholine), carbohydrate and signal transduction system (glucose, myo-inositol, galactarate) and up-regulation of citrate cycle intermediates (citrate, 2-oxoglutarate, succinate), propanoate metabolism (1,2-propanediol), amino acid metabolism (betaine, N,N-dimethylglycine, methylguanidine, valine) and nucleotide metabolism (malonate, allantoin). In summary, this study reports for the first time, C. nutans water extract is a potential anti-anaphylactic agent and 1H-NMR metabolomics is a great alternative analytical tool to explicate the mechanism of action of anaphylaxis.
    Matched MeSH terms: Disease Models, Animal
  2. Gooda Sahib Jambocus N, Saari N, Ismail A, Khatib A, Mahomoodally MF, Abdul Hamid A
    J Diabetes Res, 2016;2016:2391592.
    PMID: 26798649 DOI: 10.1155/2016/2391592
    The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60). After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a (1)H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline metabolism (betaine), creatinine metabolism (creatinine), and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline). Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment.
    Matched MeSH terms: Disease Models, Animal
  3. Zakaria ZA, Abdul Rahim MH, Roosli RAJ, Mohd Sani MH, Omar MH, Mohd Tohid SF, et al.
    Pain Res Manag, 2018;2018:9536406.
    PMID: 29686743 DOI: 10.1155/2018/9536406
    Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been proven to possess antinociceptive activity that works via the opioid and NO-dependent/cGMP-independent pathways. In the present study, we aimed to further determine the possible mechanisms of antinociception of MECN using various nociceptive assays. The antinociceptive activity of MECN was (i) tested against capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged against selective antagonist of opioid receptor subtypes (β-funaltrexamine, naltrindole, and nor-binaltorphimine); (iii) prechallenged against antagonist of nonopioid systems, namely, α2-noradrenergic (yohimbine), β-adrenergic (pindolol), adenosinergic (caffeine), dopaminergic (haloperidol), and cholinergic (atropine) receptors; (iv) prechallenged with inhibitors of various potassium channels (glibenclamide, apamin, charybdotoxin, and tetraethylammonium chloride). The results demonstrated that the orally administered MECN (100, 250, and 500 mg/kg) significantly (p < 0.05) reversed the nociceptive effect of all models in a dose-dependent manner. Moreover, the antinociceptive activity of 500 mg/kg MECN was significantly (p < 0.05) inhibited by (i) antagonists of μ-, δ-, and κ-opioid receptors; (ii) antagonists of α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and (iii) blockers of different K+ channels (voltage-activated-, Ca2+-activated, and ATP-sensitive-K+ channels, resp.). In conclusion, MECN-induced antinociception involves modulation of protein kinase C-, bradykinin-, TRVP1 receptors-, and glutamatergic-signaling pathways; opioidergic, α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and nonopioidergic receptors as well as the opening of various K+ channels. The antinociceptive activity could be associated with the presence of several flavonoid-based bioactive compounds and their synergistic action with nonvolatile bioactive compounds.
    Matched MeSH terms: Disease Models, Animal
  4. Mani V, Parle M, Ramasamy K, Abdul Majeed AB
    J Sci Food Agric, 2011 Jan 15;91(1):186-92.
    PMID: 20848667 DOI: 10.1002/jsfa.4171
    Coriandrum sativum L., commonly known as coriander and belonging to the family Apiaceae (Umbelliferae), is cultivated throughout the world for its nutritional value. The present study was undertaken to investigate the effects of fresh Coriandrum sativum leaves (CSL) on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. In this study, CSL (5, 10 and 15% w/w of diet) was fed orally with a specially prepared diet for 45 days consecutively to experimental animals. Elevated plus-maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam, scopolamine and ageing-induced amnesia served as the interoceptive behavioral models.
    Matched MeSH terms: Disease Models, Animal
  5. Mani V, Ramasamy K, Abdul Majeed AB
    Food Funct, 2013 Apr 25;4(4):557-67.
    PMID: 23360913 DOI: 10.1039/c3fo30356j
    The fresh leaves of Murraya koenigii are often added to various dishes in Asian countries due to the delicious taste and flavour that they impart. In the present study, the effect of the total alkaloidal extract from Murraya koenigii leaves (MKA) with respect to anti-inflammatory, analgesic and anti-ulcerogenic effects were evaluated using different experimental animal models. Oral supplementation of MKA at 10, 20 and 40 mg kg(-1) body weight successfully and dose-dependently reduced the formation of oedema induced by carrageenan, histamine and serotonin as well as formaldehyde-induced arthritis. In addition, the extract (10, 20 and 40 mg kg(-1), p.o.) attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and late phase of pain response induced by a subplantar injection of formalin in mice. MKA at higher doses (20 and 40 mg kg(-1), p.o) reduced the early phase response induced by formalin as well as reaction time on hot plate models. Interestingly, there was no ulcer score with the ulcerogenic effect of MKA. Moreover, all the doses of MKA (10, 20 and 40 mg kg(-1), p.o) showed promising anti-ulcerogenic activity with protection against acute gastric ulcers induced by ethanol plus hydrochloric acid and aspirin models in a dose dependent manner.
    Matched MeSH terms: Disease Models, Animal
  6. Hajrezaie M, Hassandarvish P, Moghadamtousi SZ, Gwaram NS, Golbabapour S, Najihussien A, et al.
    PLoS One, 2014;9(3):e91246.
    PMID: 24618844 DOI: 10.1371/journal.pone.0091246
    Based on the potential of Schiff base compounds to act as sources for the development of cancer chemotherapeutic agents, this in vivo study was performed to investigate the inhibitory properties of the synthetic Schiff base compound Cu(BrHAP)2 on colonic aberrant crypt foci (ACF).
    Matched MeSH terms: Disease Models, Animal
  7. Nordin N, Salama SM, Golbabapour S, Hajrezaie M, Hassandarvish P, Kamalidehghan B, et al.
    PLoS One, 2014;9(11):e111925.
    PMID: 25379712 DOI: 10.1371/journal.pone.0111925
    A natural source of medicine, Enicosanthellum pulchrum is a tropical plant which belongs to the family Annonaceae. In this study, methanol extract from the leaves and stems of this species was evaluated for its gastroprotective potential against mucosal lesions induced by ethanol in rats. Seven groups of rats were assigned, groups 1 and 2 were given Tween 20 (10% v/v) orally. Group 3 was administered omeprazole 20 mg/kg (10% Tween 20) whilst the remaining groups received the leaf and stem extracts at doses of 150 and 300 mg/kg, respectively. After an additional hour, the rats in groups 2-7 received ethanol (95% v/v; 8 mL/kg) orally while group 1 received Tween 20 (10% v/v) instead. Rats were sacrificed after 1 h and their stomachs subjected to further studies. Macroscopically and histologically, group 2 rats showed extremely severe disruption of the gastric mucosa compared to rats pre-treated with the E. pulchrum extracts based on the ulcer index, where remarkable protection was noticed. Meanwhile, a significant percentage of inhibition was shown with the stem extract at 62% (150 mg/kg) and 65% (300 mg/kg), whilst the percentage with the leaf extract at doses of 150 and 300 mg/kg was 63% and 75%, respectively. An increase in mucus content, nitric oxide, glutathione, prostaglandin E2, superoxide dismutase, protein and catalase, and a decrease in malondialdehyde level compared to group 2 were also obtained. Furthermore, immunohistochemical staining of groups 4-7 exhibited down-regulation of Bax and up-regulation of Hsp70 proteins. The methanol extract from the leaves and the stems showed notable gastroprotective potential against ethanol.
    Matched MeSH terms: Disease Models, Animal
  8. Zakaria ZA, Abdul Ghani ZD, Raden Mohd Nor RN, Gopalan HK, Sulaiman MR, Abdullah FC
    Yakugaku Zasshi, 2006 Nov;126(11):1197-203.
    PMID: 17077622
    The present study was carried out to establish the antinociceptive and anti-inflammatory properties of Dicranopteris linearis leaves chloroform extract in experimental animals. The antinociceptive activity was measured using the abdominal constriction, formalin and hot plate tests, while the anti-inflammatory activity was measured using the carrageenan-induced paw edema. The extract, obtained after 72 h soaking of the air-dried leaves in chloroform followed by evaporation under vacuo (40 degrees C) to dryness, was dissolved in dimethyl sulfoxide to the doses of 20, 100 and 200 mg/kg and administered subcutaneously 30 min prior to subjection to the above mentioned assays. The extract, at all doses used, was found to exhibit significant (p<0.05) antinociceptive activity in a dose-dependent manner. However, the significant (p<0.05) anti-inflammatory activity observed occur in a dose-independent manner. As a conclusion, the chloroform extract of D. linearis possesses antinociceptive and anti-inflammatory activity and thus justify its traditional uses by the Malays to treat various ailments.
    Matched MeSH terms: Disease Models, Animal
  9. Islam MR, Abdullah JM
    Malays J Med Sci, 2014 Dec;21(Spec Issue):34-40.
    PMID: 25941461 MyJurnal
    Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are a prognostic genetic model of absence epilepsy. This model displays the electro-clinical, behavioural, and pharmacological features of absence seizures. Although GAERS share typical characteristics, including spike-and-wave discharges (SWDs) in the electroencephalography (EEG), age-dependent studies with these animals have not yet been reported. The aim of the present study is to perform a systematic comparison contrasting the SWDs of young and older GAERS, in terms of the number, duration, frequency, and waveform morphology of the discharges, as well as the pre-SWD EEG characteristics, using identical measurement and analysis techniques. The number, cumulative total duration and mean duration of SWDs were significantly higher in young GAERS (4 to 6 months) compared to older GAERS (12 to 14 months). Furthermore, the SWD spectra and average SWD waveforms indicated that a single cycle of the SWD contains more energy in faster components, such as increased spikes and higher power, in the SWDs of the young GAERS. Additionally, older GAERS showed weak amplitude spikes in SWDs and higher power pre-SWDs. These clear morphological differences in the EEGs of young and older GAERS rats should be further examined in future studies that explore new dimensions of genetic absence epilepsy.
    Matched MeSH terms: Disease Models, Animal
  10. Albaayit SF, Abba Y, Rasedee A, Abdullah N
    Drug Des Devel Ther, 2015;9:3507-18.
    PMID: 26203223 DOI: 10.2147/DDDT.S84770
    Clausena excavata is a well-known plant used in folkloric medicine for the treatment of different ailments. This study aimed to determine the in vitro cytoxicity of its leaf solvent extracts as well as the in vivo wound healing and antioxidant activities of the methanolic extracts of C. excavata (MECE). HaCaT (keratocyte) and Vero cell lines were used for evaluation of the in vitro cytotoxic effects, while the in vivo wound healing and antioxidant activities were determined in skin wounds inflicted on rats. Twenty adult male Sprague-Dawley rats were divided into five groups of four animals each. Approximately 3.14 cm(2) excisional wound was inflicted on the nape of each rat following anesthesia. The treatment groups received topical application of MECE at 50 mg/mL (MECE-LD [low dose]), 100 mg/mL (MECE-MD [medium dose]), and 200 mg/mL (MECE-HD [high dose]), while the negative control group was treated with gum acacia in normal saline and the positive control group with intrasite gel. Wound contraction was evaluated on days 5, 10, and 15 after wound infliction, and tissue from wound area was collected at day 15 post-wound infliction for antioxidant enzyme evaluation and histopathological analyses. Generally, Vero cells were more resistant to the cytotoxic effects of the solvent extracts as compared with HaCaT cells. Chloroform (CH) and ethyl acetate (EA) extracts of C. excavata were toxic to HaCaT cells at 200 and 400 µg/mL, but the same concentrations showed higher (P<0.05) viability in Vero cells. There was significantly (P<0.01) greater wound contraction at days 10 and 15 post-wound infliction in all the treatment groups than in the control groups. Histopathologically, the MECE-HD-treated wound showed significantly (P<0.05) lesser inflammatory cell proliferation, degeneration, and distribution of granulation tissue than other groups. Similarly, the degree of collagen maturation, angiogenesis, and collagen distribution were significantly (P<0.05) lower in MECE-HD than in other groups. The MECE-HD, MECE-MD, and intrasite treatment groups showed a significantly (P<0.05) higher number of VEGF-positive and TGF-β1-positive cells in the skin wound than the control groups. The activities of superoxide dismutase and catalase were significantly (P<0.01) higher in the MECE-HD and intrasite treatment groups than in the other groups. Lipid peroxidase activity of the treated groups was significantly (P<0.01) lower than that in the control group. The study showed that MECE is a potent wound healing agent through anti-inflammatory and antioxidant effects that enhanced the rate of wound contraction, re-epithelialization, and collagen deposition. The effect of MECE is suggested to be due to its high polyphenolic compound content.
    Matched MeSH terms: Disease Models, Animal
  11. Mayakrishnan V, Kannappan P, Shanmugasundaram K, Abdullah N
    Pak J Pharm Sci, 2014 Nov;27(6):1911-7.
    PMID: 25362615
    Cyathula prostrata (Linn) Blume herbs are commonly used for the treatment of inflammatory and pain in Nigeria. The objective of the present study was to assess the antitumor and antioxidant activity of Cyathula prostrata (Linn) Blume in mice model. The treatment of Dalton's lymphoma ascites cells induced tumor by the methanolic extract of Cyathula prostrata was determined at concentration of 100 mg/ kg body weight given orally for 11 days, antitumor activity was assessed by monitoring the mean survival time, body weight, effect on hematological parameters, antioxidant enzyme levels and histopathological evidence. The results showed that the methanolic extract of Cyathula prostrata increased the survival period of animals, decreased the body weight and also altered many hematological markers and also restored the antioxidant enzymes when compared to the mice of the DLA control group. These findings indicate that the methanolic extract of C. prostrata has anti-tumor activity by preventing the lipid peroxidation and thereby promoting the antioxidant systems in Dalton's lymphoma ascites induced mice. So, these extract could be a natural anticancer agent for human health.
    Matched MeSH terms: Disease Models, Animal
  12. Mohd-Lila MA, Yee LK, Cen LS, Bala JA, Balakrishnan KN, Allaudin ZN, et al.
    Microb Pathog, 2019 Sep;134:103572.
    PMID: 31163251 DOI: 10.1016/j.micpath.2019.103572
    The common physical and chemical methods for controlling rat pest are less than satisfactory and inhumane. Immunocontraception approach has been considered more humane and it can be accomplished by inducing the relevant host immune response that block further development of reproductive gametes. ZP3 proteins are known to play very important role during sperm-ovum fertilization. It is a self-antigen and only localized in female ovaries. Therefore, an immunization with ZP3 protein elsewhere will induce a generalize host immune response against ZP3 protein. This study employed rat ZP3 (rZP3) gene prepared from its cDNA of Rattus rattus diardii. It was delivered and expressed in vivo by naked plamid DNA (DrZP3) or recombinant ZP3-Adenovirus (Ad-rZP3). Expression studies in vitro with DrZP3 or Ad-ZP3 showed rZP3 proteins were successfully expressed in Vero cells. Hyperimmune serum against rZP3 that were prepared by immunizing several rats with purified rZP3-pichia yeast fusion protein showed it blocked sperms from binding DrZP3-transfected Vero cells. Female Sprague Dawley rats immunized with DrZP3 demonstrated a long-term effect for significant reduction of fertility up to 92.6%. Ovaries from rats immunized with DrZP3 were severely atrophied with disappearance of primordial follicles from ovarian cortex with an increased in the amount of oocyte-free cell clusters. Female rats immunized with Ad-rZP3 demonstrated 27% reduction of fertility. The infertility induced by Ad-rZP3 is comparatively low and ineffective. This could be due to a strong host immune response that suppresses the recombinant virus itself resulted in minimum rZP3 protein presentation to the host immune system. As a result, low antibody titers produced against rZP3 is insufficient to block oocytes from maturity and fertilization. Therefore, immunization with DrZP3 for immunocontraception is more effective than Ad-rZP3 recombinant adenovirus. It is proposed to explore further on the use of adenovirus or other alternative viruses to deliver ZP3 protein and for the development of enhanced expression of rZP3 in target host.
    Matched MeSH terms: Disease Models, Animal
  13. Othman H, Rahman H, Mohan S, Aziz S, Marif H, Ford D, et al.
    PMID: 32922508 DOI: 10.1155/2020/8764096
    This study investigated the in vivo antileukemic activity of palladium nanoparticles (Pd@W.tea-NPs) mediated by white tea extract in a murine model. The cell viability effect of Pd@W.tea-NPs, "blank" Pd nanoparticles, and white tea extract alone was determined in murine leukemia WEHI-3B cells and normal mouse fibroblasts (3T3 cells). Apoptotic and cell cycle arrest effects of Pd@W.tea-NPs in WEHI-3B cells were evaluated. The effects of Pd@W.tea-NPs administered orally to leukemic mice at 50 and 100 mg/kg daily over 28 days were evaluated. Pd@W.tea-NPs reduced the viability of WHEI-3B cells with IC50 7.55 μg/ml at 72 h. Blank Pd nanoparticles and white tea extract alone had smaller effects on WHEI-3B viability and on normal fibroblasts. Pd@W.tea-NPs increased the proportion of Annexin V-positive WHEI-3B cells and induced G2/M cell cycle arrest. Leukemic cells in the spleen were reduced by Pd@W.tea-NPs with an increase in Bax/Bcl-2 and cytochrome-C protein and mRNA levels indicating the activation of the mitochondrial apoptotic pathway. These effects replicated the effects of ATRA and were not observed using blank Pd nanoparticles. Pd@W.tea-NPs afford therapeutic efficacy against leukemia likely to pivot on activation of the mitochondrial pathway of apoptotic signaling and hence appear attractive potential candidates for development as a novel anticancer agent.
    Matched MeSH terms: Disease Models, Animal
  14. 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: Disease Models, Animal
  15. Abubakar K, Mailafiya MM, Chiroma SM, Danmaigoro A, Zyoud TYT, Abdul Rahim E, et al.
    J Biochem Mol Toxicol, 2020 Jun;34(6):e22483.
    PMID: 32125074 DOI: 10.1002/jbt.22483
    INTRODUCTION: Lead (Pb) is a ubiquitous toxic heavy metal that inflicts numerous clinical consequences on humans. Curcumin is the principal component of turmeric, which is reported to have antioxidative properties. This study aimed at evaluating the ameliorative effects of curcumin on Pb-induced hepatorenal toxicity in a rat model.

    METHODS: Thirty-six male Sprague-Dawley rats were randomly assigned into five groups with 12 rats in the control (normal saline) and six rats each for the lead-treated group (LTG) (50 mg/kg lead acetate [Pb acetate] for 4 weeks), recovery group (50 mg/kg Pb acetate for 4 weeks and left with no treatment for another 4 weeks), treatment group 1 (Cur100) (50 mg/kg Pb acetate for 4 weeks, followed by 100 mg/kg curcumin for 4 weeks), and treatment group 2 (Cur200) (50 mg/kg Pb acetate for 4 weeks, followed by 200 mg/kg curcumin for 4 weeks). All the experimental groups received oral treatments via orogastric-tube on alternate days. Pb concentration in the liver and kidney of the rats were evaluated using inductive-coupled plasma mass spectrometry techniques.

    RESULTS: Pb-administered rats revealed significant alteration in oxidative status and increased Pb concentration in their liver and kidney with obvious reduction of hemogram and increased in leukogram as well as aberration in histological architecture of the liver and kidney. However, treatment with curcumin reduces the tissue Pb concentrations and ameliorates the above mention alterations.

    CONCLUSIONS: The results in this study suggested that curcumin attenuates Pb-induced hepatorenal toxicity via chelating activity and inhibition of oxidative stress.

    Matched MeSH terms: Disease Models, Animal
  16. García Mde L, Borrero R, Lanio ME, Tirado Y, Alvarez N, Puig A, et al.
    Biomed Res Int, 2014;2014:273129.
    PMID: 25548767 DOI: 10.1155/2014/273129
    A more effective vaccine against tuberculosis (TB) is urgently needed. Based on its high genetic homology with Mycobacterium tuberculosis (Mtb), the nonpathogenic mycobacteria, Mycobacterium smegmatis (Ms), could be an attractive source of potential antigens to be included in such a vaccine. We evaluated the capability of lipid-based preparations obtained from Ms to provide a protective response in Balb/c mice after challenge with Mtb H37Rv strain. The intratracheal model of progressive pulmonary TB was used to assess the level of protection in terms of bacterial load as well as the pathological changes in the lungs of immunized Balb/c mice following challenge with Mtb. Mice immunized with the lipid-based preparation from Ms either adjuvanted with Alum (LMs-AL) or nonadjuvanted (LMs) showed significant reductions in bacterial load (P < 0.01) compared to the negative control group (animals immunized with phosphate buffered saline (PBS)). Both lipid formulations showed the same level of protection as Bacille Calmette and Guerin (BCG). Regarding the pathologic changes in the lungs, mice immunized with both lipid formulations showed less pneumonic area when compared with the PBS group (P < 0.01) and showed similar results compared with the BCG group. These findings suggest the potential of LMs as a promising vaccine candidate against TB.
    Matched MeSH terms: Disease Models, Animal
  17. Tirado Y, Puig A, Alvarez N, Borrero R, Aguilar A, Camacho F, et al.
    Tuberculosis (Edinb), 2016 12;101:44-48.
    PMID: 27865396 DOI: 10.1016/j.tube.2016.07.017
    Tuberculosis (TB) remains an important cause of mortality and morbidity. The TB vaccine, BCG, is not fully protective against the adult form of the disease and is unable to prevent its transmission although it is still useful against severe childhood TB. Hence, the search for new vaccines is of great interest. In a previous study, we have shown that proteoliposomes obtained from Mycobacterium smegmatis (PLMs) induced cross reactive humoral and cellular response against Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the protective capability of PLMs, a murine model of progressive pulmonary TB was used. Animals immunized with PLMs with and without alum (PLMs/PLMsAL respectively) showed protection compared to non-immunized animals. Mice immunized with PLMsAL induced similar protection as that of BCG. Animals immunized with BCG, PLMs and PLMsAL showed a significant decrease in tissue damage (percentage of pneumonic area/lung) compared to non-immunized animals, with a more prominent effect in BCG vaccinated mice. The protective effect of the administration of PLMs in mice supports its future evaluation as experimental vaccine candidate against Mtb.
    Matched MeSH terms: Disease Models, Animal
  18. Mat Nor N, Guo CX, Rupenthal ID, Chen YS, Green CR, Acosta ML
    Invest Ophthalmol Vis Sci, 2018 07 02;59(8):3682-3693.
    PMID: 30029255 DOI: 10.1167/iovs.17-22829
    Purpose: To evaluate the long-term effect on inflammation and inflammasome activation of intravitreally delivered connexin43 mimetic peptide (Cx43MP) in saline or incorporated within nanoparticles (NPs) for the treatment of the light-damaged rat eye.

    Methods: Light-induced damage to the retina was created by exposure of adult albino Sprague-Dawley rats to intense light for 24 hours. A single dose of Cx43MP, Cx43MP-NPs, or saline was injected intravitreally at 2 hours after onset of light damage. Fluorescein isothiocyanate (FITC)-labelled Cx43MP-NPs were intravitreally injected to confirm delivery into the retina. Electroretinogram (ERG) recordings were performed at 24 hours, 1 week, and 2 weeks post cessation of light damage. The retinal and choroidal layers were analyzed in vivo using optical coherence tomography (OCT) and immunohistochemistry was performed on harvested tissues using glial fibrillary acidic protein (GFAP), leukocyte common antigen (CD45), and Cx43 antibodies.

    Results: FITC was visualized 30 minutes after injection in the ganglion cell layer and in the choroid. Cx43MP and Cx43MP-NP treatments improved a-wave and b-wave function of the ERG compared with saline-injected eyes at 1 week and 2 weeks post treatment, and prevented photoreceptor loss by 2 weeks post treatment. Inflammation was also reduced and this was in parallel with downregulation of Cx43 expression.

    Conclusions: The slow release of Cx43MP incorporated into NPs is more effective at treating retinal injury than a single dose of native Cx43MP in solution by reducing inflammation and maintaining both retinal structure and function. This NP preparation has clinical relevance as it reduces possible ocular complications associated with repeated intravitreal injections.

    Matched MeSH terms: Disease Models, Animal
  19. Mat Nor MN, Rupenthal ID, Green CR, Acosta ML
    Neurotherapeutics, 2020 Jan;17(1):371-387.
    PMID: 31637594 DOI: 10.1007/s13311-019-00786-5
    Increased Connexin43 hemichannel opening is associated with inflammasome pathway activation and inflammation in a range of pathologies including ocular disorders, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). In this study, the effect on retinal function and morphology of clinically safe doses of orally delivered tonabersat, a small molecule connexin hemichannel blocker, was investigated in the light-damaged retina animal model of dry AMD and in a spontaneous rat model of DR. Clinical parameters (fundus imaging, optical coherence tomography (OCT), and electroretinography) and inflammatory markers (immunohistochemistry for Iba-1 microglial marker, astrocyte marker glial fibrillary acidic protein, and Connexin43 protein expression) were assessed. Tonabersat treatment reduced inflammation in the retina in parallel with preservation of retinal photoreceptor function when assessed up to 3 months post light damage in the dry AMD model. In the DR model, clinical signs, including the presence of aneurysms confirmed using Evans blue dye perfusion, were reduced after daily tonabersat treatment for 2 weeks. Inflammation was also reduced and retinal electrical function restored. Tonabersat regulates assembly of the inflammasome (NLRP3) through Connexin43 hemichannel block, with the potential to reduce inflammation, restore vascular integrity and improve anatomical along with some functional outcomes in retinal disease.
    Matched MeSH terms: Disease Models, Animal
  20. Sulaiman MR, Zakaria ZA, Mohamad AS, Ismail M, Hidayat MT, Israf DA, et al.
    Pharm Biol, 2010 Aug;48(8):861-8.
    PMID: 20673172 DOI: 10.3109/13880200903302820
    Alpinia conchigera Griff. (Zingiberaceae), locally known to the Malays as "lengkuas ranting", is native to Peninsular Malaysia. The Malays traditionally used it to treat infection and rashes, and as a health drink. This study evaluated the analgesic and anti-inflammatory activities of the ethanol extract of A. conchigera rhizomes in mice and rats, respectively. The analgesic activity was elucidated using the acetic acid-induced writhing test, hot plate test, and formalin test, while the anti-inflammatory activity was determined using carrageenan-induced paw edema. The extract (30, 100, and 300 mg/kg) given intraperitoneally (i.p.) exhibited antinociceptive and anti-inflammatory activities in all tests used. The range of percentage of analgesia obtained for all doses of extract in the writhing test was 50-92%, and in the early and late phases of the formalin test was 25-62% and 63-98%, respectively. In addition, naloxone (5 mg/kg) given subcutaneously (s.c.) was found to reverse the extract (300 mg/kg)-induced antinociceptive activity in the writhing, hot plate, and formalin tests. Based on the results obtained, it can be concluded that the ethanol extract of A. conchigera rhizomes possessed a peripheral and central antinociceptive activity that was mediated, in part, via the opioid receptor, as well as anti-inflammatory activity.
    Matched MeSH terms: Disease Models, Animal*
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