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Fulltext Histopathological changes of acetaminophen-induced liver injury and subsequent liver regeneration in BALB/C and ICR mice

Muhammad-Azam F, Nur-Fazila SH, Ain-Fatin R, Mustapha Noordin M, Yimer N

Vet World, 2019 Nov;12(11):1682-1688.
PMID: 32009746 DOI: 10.14202/vetworld.2019.1682-1688

Background and Aim: Laboratory mice are widely used as a research model to provide insights into toxicological studies of various xenobiotic. Acetaminophen (APAP) is an antipyretic and analgesic drug that is commonly known as paracetamol, an ideal hepatotoxicant to exhibit centrilobular necrosis in laboratory mice to resemble humans. However, assessment of histopathological changes between mouse strains is important to decide the optimal mouse model used in APAP toxicity study. Therefore, we aim to assess the histomorphological features of APAP-induced liver injury (AILI) in BALB/C and Institute of Cancer Research (ICR) mice.
Materials and Methods: Twenty-five ICR mice and 20 BALB/C mice were used where five animals as control and the rest were randomly divided into four time points at 5, 10, 24 and 48 hours post-dosing (hpd). They were induced with 500 mg/kg APAP intraperitoneally. Liver sections were processed for hematoxylin-eosin staining and histopathological changes were scored based on grading methods.
Results: Intense centrilobular damage was observed as early as 5 hpd in BALB/C as compared to ICR mice, which was observed at 10 hpd. The difference of liver injury between ICR and BALB/C mice is due to dissimilarity in the genetic line-up that related to different elimination pathways of APAP toxicity. However, at 24 hpd, the damage was markedly subsided and liver regeneration had taken place for both ICR and BALB/C groups with evidence of mitotic figures. This study showed that normal liver architecture was restored after the clearance of toxic insult.
Conclusion: AILI was exhibited earlier in BALB/C than ICR mice but both underwent liver recovery at later time points.
Experimental Brachiaria decumbens toxicity in cattle

Noordin MM, Salam Abdullah A, Rajion MA

Vet Res Commun, 1989;13(6):491-4.
PMID: 2631385

Although Brachiaria decumbens was not toxic when fed to cattle, the infusion of rumen liquor from B. decumbens intoxicated sheep into the rumen of cattle produced evidence suggesting hepatic and renal dysfunction. Several biochemical changes were observed including increases in serum aspartate amino transferase, serum creatinine and blood urea nitrogen and a marked reduction in the plasma bromosulphthalein clearance.
The concentration of selected minerals and phytate in Malaysian Brachiaria decumbens

Noordin MM, Zhang SS, Rahman SO, Haron J

Vet Hum Toxicol, 2000 Oct;42(5):276-9.
PMID: 11003117

Samples of Brachiaria decumbens collected from 5 farms representing the Peninsular Malaysia were subjected to selected trace mineral and phytate analyses to explain the pathogenesis of B decumbens intoxication. Concentrations of Cu, Zn, Fe and Mo were comparable to other grasses while that of phytate was low. The molar ratios of Cu:Zn, Cu:Mo, and Cu:Fe warrant that Cu deficiency is involved in the toxicity of B decumbens. This might aggravate the development of photosensitization of unpigmented or lightly pigmented areas of affected animals. The Zn:phytate ratio could predispose to Zn deficiency during intoxication.
Effects of copper overload on hepatic lipid peroxidation and antioxidant defense in rats

Zhang SS, Noordin MM, Rahman SO, Haron J

Vet Hum Toxicol, 2000 Oct;42(5):261-4.
PMID: 11003114

The influence of copper (Cu) overload on hepatic lipid peroxidation and antioxidation defense capacity was studied by overloading rats with copper sulphate orally (500 mg Cu/kg bw) 5 d/w for 8 w. Malondialdehyde (MDA), Cu-Zn superoxide dismutase (SOD), and Se-glutathione peroxidase (GSH-Px) were measured in serum and liver homogenate at 2, 4 and 8 w of dosing. Liver Cu concentration and alanine aminotransferase (ALT) activity were also determined. As Cu loading progressed, there were multiparameter changes with significant ALT elevation, increased MDA concentrations in serum and liver homogenate, and dramatic declines of SOD and GSH-Px activities in erythrocytes and whole blood respectively, along with marked elevation of hepatic Cu in the Cu-dosed group. Excessive Cu accumulation in the liver depressed SOD and GSH-Px activities and resulted in high MDA in serum and liver homogenate due to the lipid peroxidation induced by the Cu overload.
The effect of zinc supplementation on antioxidant and lipid peroxidation status during Brachiaria decumbens intoxication in sheep

Zhang SS, Noordin MM, Rahman SO, Haron MJ

Vet Hum Toxicol, 2001 Apr;43(2):83-7.
PMID: 11308125

An attempt was made to clarify the association between zinc (Zn) and antioxidants due to Zn supplementation on lipid peroxidation occurring during Brachiaria decumbens intoxication. The concentration of Zn, copper, malondialdehyde (MDA), superoxide dismutase (SOD), and gluthathione peroxidase (GSH-Px) were determined in tissues. There was a gradual increment in the concentration of Zn and MDA in serum and hepatocytic SOD in groups given Zn + B decumbens. A decline in erythrocytic GSH-Px and SOD, and lower concentration of reduced glutathione in hepatocyte cytosols were also detected in these sheep. It is highly suggestive that Zn supplementation may depress antioxidant status and enhance lipid peroxidation during B decumbens intoxication.
Neurological disorders in sheep during signal grass (Brachiaria decumbens) toxicity

Abdullah AS, Noordin MM, Rajion MA

Vet Hum Toxicol, 1989 Apr;31(2):128-9.
PMID: 2929118

Severe neurological dysfunction was observed in sheep 4 weeks after grazing on Signal grass (Brachiaria decumbens). These neurological disorders included the stamping of forelegs, star-gazing, incoordination, head-pressing against the fence and circling movements. Histologically, numerous vacuolations of various sizes were observed in the white matter of the brain giving rise to a spongy appearance.
Toxoplasma gondii infection in native village chickens (Gallus domesticus) in Selangor and Melaka, Malaysia

Sabri AR, Hassan L, Sharma RSK, Noordin MM

Trop Biomed, 2019 Sep 01;36(3):604-609.
PMID: 33597482

Toxoplasmosis is a worldwide zoonosis caused by the protozoa Toxoplasma gondii which affects human and animals. Village chickens (Gallus domesticus) most commonly known as Ayam Kampung or free-range chickens, have been suggested to play a role in the epidemiology of toxoplasmosis. This study determines the presence of T. gondii in the village chicken populations in two states of Malaysia. A total of 50 serum samples from the chickens from Selangor (n=20) and Melaka (n=30) were collected and analysed using commercial serological kits. T. gondii antigen was detected in 20% (Selangor 30%; Melaka 13%) samples using ELISA test and anti-T. gondii antibody was detected in all positive ELISA samples using the indirect haemagglutination test (IHAT). Histopathological examination revealed tissue changes such as inflammation and degeneration in brain and liver of seropositive chickens. This is the first report of T. gondii infection in the village chickens in Malaysia.
DNA damage and adduct formation in immune organs of developing chicks by polycyclic aromatic hydrocarbons

Nisha AR, Hazilawati H, Mohd Azmi ML, Noordin MM

Toxicol. Mech. Methods, 2017 Mar;27(3):215-222.
PMID: 28030985 DOI: 10.1080/15376516.2016.1273432

Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants and chemically a class of structurally similar chemical compounds characterized by the presence of fused aromatic rings. This research was undertaken to find out immunotoxic effects produced by pyrene, phenanthrene and fluoranthene. These chemicals were injected into developing chicks at three dose levels (0.2, 2 and 20 mg per kg) through allantioc route to rule out possible mechanisms involved in immunotoxicity. DNA adduct produced by PAHs in immune organs were analyzed by DNA adduct enzyme-linked immunosorbent assay (ELISA) kit and DNA damage was assessed by comet assay. A significant increase in the DNA adduct levels was found in thymus and bursa in 2 mg and 20 mg dose levels of pyrene, fluoranthene and phenanthrene treated groups, whereas those in spleen simulated the value of controls. Comet assay indicated that PAHs especially pyrene, fluoranthene and phenanthrene were capable of inducing increased level of comet parameters in thymus at all the dose levels. Bursa of Fabricius and spleen also showed a gradual rise in comet parameters corresponding to all dose levels, but the increase was more marked as in thymus. Thus, it can be concluded that DNA adducts produced by PAHs lead to single-strand breaks and reduced DNA repair, which ultimately begin a carcinogenic process. Hence, this experiment can be considered as a strong evidence of genotoxic potential of PAHs like pyrene, phenanthrene and fluoranthene in developing chicks.
The induction of aryl hydrocarbon receptor (AHR) in immune organs of developing chicks by polycyclic aromatic hydrocarbons

Nisha AR, Hazilawati H, Mohd Azmi ML, Noordin MM

Toxicol. Mech. Methods, 2018 Jul;28(6):461-466.
PMID: 29606035 DOI: 10.1080/15376516.2018.1459992

Polycyclic aromatic hydrocarbons are pollutants which are persistent in nature. The aryl hydrocarbon receptor is a ligand-activated cytosolic transcription factor activated by xenobiotics. The objective was to isolate and identify AHR mRNA transcript in immune organs of developing chicks and to interpret the correlation between AHR induction and dose of PAHs. Specific pathogen free embryonated eggs on day nine were inoculated with solutions of pyrene, phenanthrene, and fluoranthene dissolved in tricaprylin (vehicle) through the allantoic route at three dose levels: 0.2 mg/kg, 2 mg/kg, and 20 mg/kg. A 650 base pair product was observed by RNA extraction and reverse transcription PCR from thymus, bursa of Fabricius and spleen on 21st day. When AHR concentration was analyzed by ELISA in these organs, pyrene showed maximum potency in inducing AHR in thymus. Fluoranthene made highest concentration of AHR in bursa of Fabricius. None of these chemicals caused an increase in AHR concentration in spleen.
Fulltext Quantitative analysis of electroplated nickel coating on hard metal

Wahab HA, Noordin MY, Izman S, Kurniawan D

ScientificWorldJournal, 2013;2013:631936.
PMID: 23997678 DOI: 10.1155/2013/631936

Electroplated nickel coating on cemented carbide is a potential pretreatment technique for providing an interlayer prior to diamond deposition on the hard metal substrate. The electroplated nickel coating is expected to be of high quality, for example, indicated by having adequate thickness and uniformity. Electroplating parameters should be set accordingly for this purpose. In this study, the gap distances between the electrodes and duration of electroplating process are the investigated variables. Their effect on the coating thickness and uniformity was analyzed and quantified using design of experiment. The nickel deposition was carried out by electroplating in a standard Watt's solution keeping other plating parameters (current: 0.1 Amp, electric potential: 1.0 V, and pH: 3.5) constant. The gap distance between anode and cathode varied at 5, 10, and 15 mm, while the plating time was 10, 20, and 30 minutes. Coating thickness was found to be proportional to the plating time and inversely proportional to the electrode gap distance, while the uniformity tends to improve at a large electrode gap. Empirical models of both coating thickness and uniformity were developed within the ranges of the gap distance and plating time settings, and an optimized solution was determined using these models.
Fulltext Neofusicoccum ribis Associated with Leaf Blight on Rubber (Hevea brasiliensis) in Peninsular Malaysia

Nyaka Ngobisa AI, Zainal Abidin MA, Wong MY, Wan Noordin MW

Plant Pathol J, 2013 Mar;29(1):10-6.
PMID: 25288924 DOI: 10.5423/PPJ.OA.07.2012.0110

Hevea brasiliensis is a natural source of rubber and an important plantation tree species in Malaysia. Leaf blight disease caused by Fusicoccum substantially reduces the growth and performance of H. brasiliensis. The aim of this study was to use a combination of both morphological characteristics and molecular data to clarify the taxonomic position of the fungus associated with leaf blight disease. Fusicoccum species were isolated from infected leaves collected from plantations at 3 widely separated locations - Selangor, Perak, and Johor states - in Peninsular Malaysia in 2010. All the isolates were identified according to their conidial patterns and DNA sequences generated from internal transcribed spacers (ITS1 and ITS2), the 5.8S rRNA, and an unknown locus (BotF15) containing microsatellite repeats. Based on taxonomic and sequence data, Neofusicoccum ribis was identified as the main cause of leaf blight disease in H. brasiliensis in commercial plantations in Malaysia. A pathogenicity trial on detached leaves further confirmed that N. ribis causes leaf blight disease. N. ribis is an important leaf pathogen, and its detection in Malaysia has important implications for future planting of H. brasiliensis.
Fulltext Portal biliopathy

Ho C, Gunn A, Noordin M

Med J Malaysia, 2014 Oct;69(5):236-7.
PMID: 25638241 MyJurnal

Portal biliopathy is a term to describe the spectrum of abnormalities of the entire biliary tract or gallbladder associated with portal hypertension. The most common cause of portal biliopathy is extra-hepatic portal vein obstruction (EHPVO). We report a case of patient with portal biliopathy presenting with bleeding varices.
Mineral and physichocemical characterization of cockle (Anadara granosa) shells as an alternative biomaterial for bone tissue engineering

Hazmi AJ, Zuki AB, Noordin MM, Jalila A, Norimah Y

Med J Malaysia, 2008 Jul;63 Suppl A:93-4.
PMID: 19025000

This study was conducted based on the hypothesis that mineral and physicochemical properties of cockle shells similarly resemble the properties of corals (Porites sp.). Hence, the mineral and physicochemical evaluations of cockle shells were conducted to support the aforementioned hypothesis. The results indicated that cockle shells and coral exoskeleton shared similar mineral and physicochemical properties.
Glycerol preserved bovine pericardium for abdominal wall reconstruction: experimental study in rat model

Hafeez YM, Zuki AB, Loqman MY, Yusof N, Asnah H, Noordin MM

Med J Malaysia, 2004 May;59 Suppl B:117-8.
PMID: 15468846

The aim of this study was to evaluate bovine pericardium surgical patch in rat model. Bovine pericardial sacs collected from local abattoir were cleaned, disinfected and cut into pieces of 3 by 2.5cm and preserved in 99.5% glycerol. Full thickness abdominal wall defects of 3 by 2.5 cm were created in 30 adult male Sprague Dawley rats and repaired with glycerol preserved pieces. The rats were serially sacrificed in a group of six rats at 1,3,6,9 and 18 weeks post-surgical intervals for morphological and tensometeric study. Macroscopically, no mortality or postoperative surgical complications was encountered except slight adhesions between implanted grafts and some visceral organs in 10% of the rats. Microscopically no calcification or foreign body giant cell formation was found in the explanted grafts. The implanted grafts were replaced gradually with recipient tissue, which made mainly of dense collagenous bundles. The healing strength between the implanted grafts and the recipient abdominal wall was gradually increased with time. The results of this study showed that glycerol preserved bovine pericardium act as scaffold for transformation into living tissue without clinical complications such as that associated with prostheses.
Chronic toxicity evaluation of Morinda citrifolia fruit and leaf in mice

Mohamad Shalan NAA, Mustapha NM, Mohamed S

Regul Toxicol Pharmacol, 2017 Feb;83:46-53.
PMID: 27871867 DOI: 10.1016/j.yrtph.2016.11.022

Noni (Morinda citrifolia) leaf and fruit are used as food and medicine. This report compares the chronic toxicity of Noni fruit and edible leaf water extracts (two doses each) in female mice. The 6 months study showed the fruit extract produced chronic toxicity effects at the high dose of 2 mg/ml drinking water, evidenced through deteriorated liver histology (hepatocyte necrosis), reduced liver length, increased liver injury marker AST (aspartate aminotransferase) and albumin reduction, injury symptoms (hypoactivity, excessive grooming, sunken eyes and hunched posture) and 40% mortality within 3 months. This hepatotoxicity results support the six liver injury reports in humans which were linked to chronic noni fruit juice consumption. Both doses of the leaf extracts demonstrated no observable toxicity. The hepatotoxicity effects of the M. citrifolia fruit extract in this study is unknown and may probably be due to the anthraquinones in the seeds and skin, which had potent quinone reductase inducer activity that reportedly was 40 times more effective than l-sulforaphane. This report will add to current data on the chronic toxicity cases of Morinda citrifolia fruit. No report on the chronic toxicity of Morinda citrifolia fruit in animal model is available for comparison.
Machining of bone: Analysis of cutting force and surface roughness by turning process

Noordin MY, Jiawkok N, Ndaruhadi PY, Kurniawan D

Proc Inst Mech Eng H, 2015 Nov;229(11):761-8.
PMID: 26399875 DOI: 10.1177/0954411915606169

There are millions of orthopedic surgeries and dental implantation procedures performed every year globally. Most of them involve machining of bones and cartilage. However, theoretical and analytical study on bone machining is lagging behind its practice and implementation. This study views bone machining as a machining process with bovine bone as the workpiece material. Turning process which makes the basis of the actually used drilling process was experimented. The focus is on evaluating the effects of three machining parameters, that is, cutting speed, feed, and depth of cut, to machining responses, that is, cutting forces and surface roughness resulted by the turning process. Response surface methodology was used to quantify the relation between the machining parameters and the machining responses. The turning process was done at various cutting speeds (29-156 m/min), depths of cut (0.03 -0.37 mm), and feeds (0.023-0.11 mm/rev). Empirical models of the resulted cutting force and surface roughness as the functions of cutting speed, depth of cut, and feed were developed. Observation using the developed empirical models found that within the range of machining parameters evaluated, the most influential machining parameter to the cutting force is depth of cut, followed by feed and cutting speed. The lowest cutting force was obtained at the lowest cutting speed, lowest depth of cut, and highest feed setting. For surface roughness, feed is the most significant machining condition, followed by cutting speed, and with depth of cut showed no effect. The finest surface finish was obtained at the lowest cutting speed and feed setting.
A review of evolution of electrospun tissue engineering scaffold: From two dimensions to three dimensions

Ngadiman NHA, Noordin MY, Idris A, Kurniawan D

Proc Inst Mech Eng H, 2017 Jul;231(7):597-616.
PMID: 28347262 DOI: 10.1177/0954411917699021

The potential of electrospinning process to fabricate ultrafine fibers as building blocks for tissue engineering scaffolds is well recognized. The scaffold construct produced by electrospinning process depends on the quality of the fibers. In electrospinning, material selection and parameter setting are among many factors that contribute to the quality of the ultrafine fibers, which eventually determine the performance of the tissue engineering scaffolds. The major challenge of conventional electrospun scaffolds is the nature of electrospinning process which can only produce two-dimensional electrospun mats, hence limiting their applications. Researchers have started to focus on overcoming this limitation by combining electrospinning with other techniques to fabricate three-dimensional scaffold constructs. This article reviews various polymeric materials and their composites/blends that have been successfully electrospun for tissue engineering scaffolds, their mechanical properties, and the various parameters settings that influence the fiber morphology. This review also highlights the secondary processes to electrospinning that have been used to develop three-dimensional tissue engineering scaffolds as well as the steps undertaken to overcome electrospinning limitations.
Fulltext Pulmonary modulation of benzo[a]pyrene-induced hemato- and hepatotoxicity in broilers

Latif IK, Karim AJ, Zuki AB, Zamri-Saad M, Niu JP, Noordin MM

Poult Sci, 2010 Jul;89(7):1379-88.
PMID: 20548065 DOI: 10.3382/ps.2009-00622

Aftermath in several air pollution episodes with high concentrations of polycyclic aromatic hydrocarbons did not significantly affect health and performance of broilers despite its renowned sensitivity to polycyclic aromatic hydrocarbons. The aim of the study was to elucidate the previous lack of response in birds exposed to such severe episodes of air pollution. Benzo[a]pyrene (BaP) was used to simulate the influence of air pollution on hematology, selected organ function, and oxidative stress in broilers. One-day-old chicks were assigned to 5 equal groups composed of a control group, tricaprylin group, and 3 groups treated with BaP (at 1.5 microg, 150 microg, or 15 mg/kg of BW). The BaP was intratracheally administered to 1-d-old chicks for 5 consecutive days. The hematology, liver and kidney function, P450 activity, and malondialdehyde level especially in the group receiving 15 mg of BaP/kg of BW demonstrated evidence of hemato- and hepatoxicity via BaP-induced oxidative stress. The deleterious effect of exposure to high concentration of BaP in broiler chickens was probably due to the anatomy of this species and the half-life of BaP. Although the effect of BaP may be transient or irreversible, pathogen challenges faced during the period of suppression may prove fatal.
Fulltext Chemopreventive Activity of Ferulago angulate against Breast Tumor in Rats and the Apoptotic Effect of Polycerasoidin in MCF7 Cells: A Bioassay-Guided Approach

Karimian H, Fadaeinasab M, Zorofchian Moghadamtousi S, Hajrezaei M, Razavi M, Safi SZ, et al.

PLoS One, 2015;10(5):e0127434.
PMID: 25996383 DOI: 10.1371/journal.pone.0127434

Ferulago angulata leaf hexane extract (FALHE) was found to be a potent inducer of MCF7 cell apoptosis. The aims of the present study were to investigate the in vivo chemopreventive effect of FALHE in rats, to identify the contributing anticancer compound in FALHE and to determine its potential mechanism of action against MCF7 cells. Thirty rats harboring LA7-induced breast tumors were divided into five groups: tumor control, low-dose FALHE, high-dose FALHE, treatment control (tamoxifen) and normal control. Breast tissues were then subjected to histopathological and immunohistochemical analyses. A bioassay-guided investigation on FALHE was performed to identify the cytotoxic compound and its mechanism of action through flow cytometry, real-time qPCR and western blotting analyses. An in vivo study showed that FALHE suppressed the expression of the tumor markers PCNA and Ki67. The tumor size was reduced from 2031 ± 281 mm3 to 432 ± 201 mm3 after FALHE treatment. FALHE administration induced apoptosis in breast tumor cells, and this was confirmed by high expression levels of Bax, p53 and caspase 3. Cell cycle arrest was suggested by the expression of p21 and p27. The in vitro experimental results resulted in the isolation of polycerasoidin as a bioactive ingredient of FALHE with an IC50 value of 3.16 ± 0.31 μg/ml against MCF7 cells. Polycerasoidin induced mitochondrial-dependent apoptosis in breast cancer cells via caspase activation and changes in the mRNA and protein expression of Bax and Bcl-2. In addition, flow cytometric analysis demonstrated that the treated MCF7 cells were arrested at the G1 phase, and this was associated with the up-regulation of p21 and p27 at both the mRNA and protein levels. The results of the present study reinforce further investigations scrutinizing the promising potential of the F. angulata chemical constituents as breast cancer chemopreventive agents.
Noni leaf and black tea enhance bone regeneration in estrogen-deficient rats

Shalan NA, Mustapha NM, Mohamed S

Nutrition, 2017 Jan;33:42-51.
PMID: 27908549 DOI: 10.1016/j.nut.2016.08.006

OBJECTIVE: Black tea and Nonileaf are among the dietary compounds that can benefit patients with bone resorption disorders. Their bone regeneration effects and their mechanisms were studied in estrogen-deficient rats.
METHODS: Noni leaves (three doses) and black tea water extracts were fed to ovariectomized rats for 4 mo, and their effects (analyzed via mechanical measurements, micro-computed tomography scan, and reverse transcriptase polymerase chain reaction mRNA) were compared with Remifemin (a commercial phytoestrogen product from black cohosh).
RESULTS: The water extracts (dose-dependently for noni leaves) increased bone regeneration biomarker (runt-related transcription factor 2, bone morphogenetic protein 2, osteoprotegerin, estrogen receptor 1 [ESR1], collagen type I alpha 1A) expressions and reduced the inflammatory biomarkers (interleukin-6, tumor necrosis factor-α, nuclear factor [NF]-κB, and receptor activator of NF-κB ligand) mRNA expressions/levels in the rats. The extracts also improved bone physical and mechanical properties. The extracts demonstrated bone regeneration through improving bone size and structure, bone mechanical properties (strength and flexibility), and bone mineralization and density.
CONCLUSIONS: The catechin-rich extract favored bone regeneration and suppressed bone resorption. The mechanisms involved enhancing osteoblast generation and survival, inhibiting osteoclast growth and activities, suppressing inflammation, improving bone collagen synthesis and upregulating ESR1 expression to augment phytoestrogenic effects. Estrogen deficiency bone loss and all extracts studied (best effect from Morinda leaf at 300 mg/kg body weight) mitigated the loss, indicating benefits for the aged and menopausal women.

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