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Neuroprotective effect of poly(lactic-co-glycolic acid) nanoparticle-bound brain-derived neurotrophic factor in a permanent middle cerebral artery occlusion model of ischemia in rats

Kamarudin SN, Iezhitsa I, Tripathy M, Alyautdin R, Ismail NM

Acta Neurobiol Exp (Wars), 2020;80(1):1-18.
PMID: 32214270

Poly (lactide‑co‑glycolide) (PLGA) nanoparticles (NPs) are biodegradable carriers that participate in the transport of neuroprotective drugs across the blood brain barrier (BBB). Targeted brain‑derived neurotrophic factor (BDNF) delivery across the BBB could provide neuroprotection in brain injury. We tested the neuroprotective effect of PLGA nanoparticle‑bound BDNF in a permanent middle cerebral artery occlusion (pMCAO) model of ischemia in rats. Sprague‑Dawley rats were subjected to pMCAO. Four hours after pMCAO, two groups were intravenously treated with BDNF and NP‑BDNF, respectively. Functional outcome was assessed at 2 and 24 h after pMCAO, using the modified neurologic severity score (mNSS) and rotarod performance tests. Following functional assessments, rats were euthanized blood was taken to assess levels of the neurobiomarkers neuron‑specific enolase and S100 calcium‑binding protein β (S100β), and the brain was evaluated to measure the infarct volume. The NP‑BDNF‑treated group showed significant improvement in mNSS compared with pMCAO and BDNF‑treated groups and showed improved rotarod performance. The infarct volume in rats treated with NP‑BDNFs was also significantly smaller. These results were further corroborated by correlating differences in estimated NSE and S100β. NP‑BDNFs exhibit a significant neuroprotective effect in the pMCAO model of ischemia in rats.
Taurine protects against NMDA-induced retinal damage by reducing retinal oxidative stress

Jafri AJA, Agarwal R, Iezhitsa I, Agarwal P, Ismail NM

Amino Acids, 2019 Apr;51(4):641-646.
PMID: 30656415 DOI: 10.1007/s00726-019-02696-4

This study aimed to evaluate effect of TAU on NMDA-induced changes in retinal redox status, retinal cell apoptosis and retinal morphology in Sprague-Dawley rats. Taurine was injected intravitreally as pre-, co- or post-treatment with NMDA and 7 days post-treatment retinae were processed for estimation of oxidative stress, retinal morphology using H&E staining and retinal cell apoptosis using TUNEL staining. Treatment with TAU, particularly pre-treatment, significantly increased retinal glutathione, superoxide dismutase and catalase levels compared to NMDA-treated rats; whereas, the levels of malondialdehyde reduced significantly. Reduction in retinal oxidative stress in TAU pre-treated group was associated with significantly greater fractional thickness of ganglion cell layer within inner retina and retinal cell density in inner retina. TUNEL staining showed significantly reduced apoptotic cell count in TAU pre-treated group compared to NMDA group. It could be concluded that TAU protects against NMDA-induced retinal injury in rats by reducing retinal oxidative stress.
The subcellular localisation and the time course of bismuth in the gastric mucosa of rats after short-term administration of colloidal bismuth subcitrate

Ismail NM, Mustapha MS, Megat R

Ann Acad Med Singap, 1997 Nov;26(6):754-7.
PMID: 9522974

The aim of this study was to investigate if colloidal bismuth subcitrate (CBS) can penetrate the gastric mucus barrier to reach the different sites of the antral mucosa and to estimate the time course for CBS to reach and remain in the mucosa. A single dose of CBS was administered orally to rats that were sacrificed at different time intervals post treatment. The control group received gum acacia without CBS. Colloidal bismuth subcitrate, visualised as electron dense precipitate (EDP), was seen in the gastric mucus layer, intercellular spaces and intracellularly after 30 minutes and disappeared after 6 hours. Scant amounts of EDP were observed in the gastric crypts, confined only to the upper parts of these structures. We concluded that CBS can penetrate the mucus and has a wide but uneven distribution in the gastric mucosa. Colloidal bismuth subcitrate, in the concentration given only penetrated the upper two-thirds of gastric pits and not the lower one-third. We also concluded that CBS has to be given 6 hourly to ensure its continuous presence in the gastric mucosa.
Fulltext Effects of captopril on factors affecting gastric mucosal integrity in aspirin-induced gastric lesions in Sprague-Dawley rats

Ismail NM, Ibrahim IA, Hashim NB, Jaarin K

Arch Med Sci, 2013 Dec 30;9(6):1132-7.
PMID: 24482662 DOI: 10.5114/aoms.2012.31252

INTRODUCTION: Captopril is an angiotensin-converting enzyme inhibitor, which is used as an antihypertensive agent and has shown antioxidant properties. This study aims at determining the effects of captopril on factors affecting gastric mucosal integrity in aspirin-induced gastric lesions.
MATERIAL AND METHODS: Eighteen male Sprague-Dawley (200-250 g) rats that were given aspirin (40 mg/100 g body weight) were divided into three groups: the control, captopril (1 mg/100 g body weight daily) and ranitidine (2.5 mg/100 g body weight twice daily) groups. Ranitidine and captopril were given orally for 28 days. Rats in all groups were sacrificed and the parameters measured.
RESULTS: Captopril reduced gastric acidity, and increased gastric glutathione (GSH) and prostaglandin E2 (PGE2) significantly in comparison to the control group. Captopril also reduced malondialdehyde (MDA) and gastric lesions insignificantly compared to the control group. Ranitidine healed the lesions significantly compared to the control group. There was no difference between ranitidine and captopril on the severity of lesions, gastric acidity, MDA and GSH. Captopril increased PGE2 compared to ranitidine (p < 0.05).
CONCLUSIONS: Captopril has desirable effects on the factors affecting gastric mucosal integrity (acidity, PGE2 and GSH) and is comparable to ranitidine in ulcer healing.
KEYWORDS: aspirin; captopril; gastric lesions; ranitidine
Palm vitamin E and the healing of ethanol-induced gastric lesions

Ismail NM, Jaarin K, Ahmad A, Marzuki A, Ng WK, Gapor MT

Asia Pac J Clin Nutr, 1999 Dec;8(4):258-62.
PMID: 24394225

The main focus of the study was to examine the effect of palm vitamin E (a tocotrienol-enriched fraction of palm oil) on the healing of ethanol-induced gastric mucosal lesions. The study was divided into three sections.Study 1 determined the gastric content of vitamin E after dietary supplementation with palm vitamin E for 3 weeks. Seven rats were fed a normal diet and another 7 were fed a palm vitamin E-enriched diet (150 mg/kg food). The gastric content of vitamin E levels were higher in rats fed with a palm vitamin E-enriched diet (p<0.01). Study 2 determined the time-dependent effects of palm vitamin E on gastric lesions and gastric acidity postethanol administration. Two groups of rats were fed either a normal rat diet or a palm vitamin E-enriched diet (150 mg/kg food). After 3 weeks, the control and a treated group received a single intragastric dose of 100% ethanol. Assessment of gastric lesions after 1 week showed a lower gastric lesion index in the palm vitamin E group compared with the controls (p<0.05) but there was no difference in the gastric acid content after 1 week between the two groups. Study 3 determined the effects of palm vitamin E on the gastric tissue content of malondialdehyde (MDA), PGE2 and gastric acidity without ethanol administration. The MDA content was lower in the palm vitamin E-treated group (p<0.05). However, the gastric acid and PGE2 content in both groups did not differ. The findings suggest that feeding with a palm vitamin E-enriched diet (150 mg/kg food) for 3 weeks resulted in a significant concentration of vitamin E in the gastric tissue. It was concluded that palm vitamin E may promote the healing of ethanol-induced gastric lesions through minimizing the lipid preoccupation process in the gastric mucous.
Fulltext Antiproliferative effect of Tualang honey on oral squamous cell carcinoma and osteosarcoma cell lines

Ghashm AA, Othman NH, Khattak MN, Ismail NM, Saini R

BMC Complement Altern Med, 2010;10:49.
PMID: 20840769 DOI: 10.1186/1472-6882-10-49

The treatment of oral squamous cell carcinomas (OSCC) and human osteosarcoma (HOS) includes surgery and/or radiotherapy which often lead to reduced quality of life. This study was aimed to study the antiproliferative activity of local honey (Tualang) on OSCC and HOS cell lines.
Fulltext Protective Effect of Palm Oil-Derived Tocotrienol-Rich Fraction Against Retinal Neurodegenerative Changes in Rats with Streptozotocin-Induced Diabetic Retinopathy

Sadikan MZ, Nasir NAA, Agarwal R, Ismail NM

Biomolecules, 2020 04 05;10(4).
PMID: 32260544 DOI: 10.3390/biom10040556

: Oxidative stress plays an important role in retinal neurodegeneration and angiogenesis associated with diabetes. In this study, we investigated the effect of the tocotrienol-rich fraction (TRF), a potent antioxidant, against diabetes-induced changes in retinal layer thickness (RLT), retinal cell count (RCC), retinal cell apoptosis, and retinal expression of vascular endothelial growth factor (VEGF) in rats. Additionally, the efficacy of TRF after administration by two different routes was compared. The diabetes was induced in Sprague-Dawley rats by intraperitoneal injection of streptozotocin. Subsequently, diabetic rats received either oral or topical treatment with vehicle or TRF. Additionally, a group of non-diabetic rats was included with either oral or topical treatment with a vehicle. After 12 weeks of the treatment period, rats were euthanized, and retinas were collected for measurement of RLT, RCC, retinal cell apoptosis, and VEGF expression. RLT and RCC in the ganglion cell layer were reduced in all diabetic groups compared to control groups (p < 0.01). However, at the end of the experimental period, oral TRF-treated rats showed a significantly greater RLT compared to topical TRF-treated rats. A similar observation was made for retinal cell apoptosis and VEGF expression. In conclusion, oral TRF supplementation protects against retinal degenerative changes and an increase in VEGF expression in rats with streptozotocin-induced diabetic retinopathy. Similar effects were not observed after topical administration of TRF.
Role of adenosine receptors in resveratrol-induced intraocular pressure lowering in rats with steroid-induced ocular hypertension

Razali N, Agarwal R, Agarwal P, Kumar S, Tripathy M, Vasudevan S, et al.

Clin Exp Ophthalmol, 2015 Jan-Feb;43(1):54-66.
PMID: 24995479 DOI: 10.1111/ceo.12375

BACKGROUND: Steroid-induced ocular hypertension is currently treated in the same way as primary open-angle glaucoma. However, the treatment is often suboptimal and is associated with adverse effects. We evaluated the oculohypotensive effects of topical trans-resveratrol in rats with steroid-induced ocular hypertension and involvement of adenosine receptors (AR) in intraocular pressure (IOP) lowering effect of trans-resveratrol.
METHODS: The oculohypotensive effect of unilateral single-drop application of various concentrations of trans-resveratrol was first studied in oculonormotensive rats. Concentration with maximum effect was similarly studied in rats with steroid-induced ocular hypertension. Involvement of AR was studied by observing the alterations of IOP in response to trans-resveratrol after pretreating animals with AR subtype-specific antagonists. Additionally, we used computational methods, including 3D modelling, 3D structure generation and protein-ligand interaction, to determine the AR-trans-resveratrol interaction.
RESULTS: All concentrations of trans-resveratrol produced significant IOP reduction in normotensive rat eyes. Maximum mean IOP reduction of 15.1% was achieved with trans-resveratrol 0.2%. In oculohypertensive rats, trans-resveratrol 0.2% produced peak IOP reduction of 25.2%. Pretreatment with A₁ antagonist abolished the oculohypotensive effect of trans-resveratrol. Pretreatment with A₃ and A₂A AR antagonists produced significant IOP reduction in both treated and control eyes, which was further augmented by trans-resveratrol application in treated eyes. Computational studies showed that trans-resveratrol has highest affinity for A₂B and A₁, followed by A2A and A₃ AR.
CONCLUSION: Topically applied trans-resveratrol reduces IOP in rats with steroid-induced ocular hypertension. Trans-resveratrol-induced oculohypotension involves its agonistic activity at the A₁ AR.
KEYWORDS: adenosine receptors; docking simulation; intraocular pressure; resveratrol; topical
Oral mucosal lesions in non oral habit diabetic patients and association of diabetes mellitus with oral precancerous lesions

Saini R, Al-Maweri SA, Saini D, Ismail NM, Ismail AR

Diabetes Res Clin Pract, 2010 Sep;89(3):320-6.
PMID: 20488573 DOI: 10.1016/j.diabres.2010.04.016

AIMS: This study was aimed to determine the prevalence of oral mucosal lesions (OML) in patients with diabetes mellitus (DM) and non-diabetic subjects without any oral habits and to investigate the association of DM with oral precancerous lesions.
METHODS: This cross-sectional study involved 420 diabetic and 420 non-diabetic control subjects without any oral habits. Detailed oral examination was performed based on international criteria.
RESULTS: A significantly greater proportion of subjects with DM (45%) had one or more OML in comparison to non-diabetics (38.3%). Patients with DM showed a significantly greater prevalence of geographic tongue, denture stomatitis and angular cheilitis than non-diabetics (p<0.05). The results also showed an association between occurrence of one or more OML and metabolic control of diabetic patients (p<0.05). For precancerous lesions, lichen planus was found in two diabetic patients while none of controls had any precancerous lesion (p>0.05).
CONCLUSIONS: Prevalence of OML was significantly higher in diabetic patients than non-diabetics and this prevalence was associated with the metabolic control of the patients. However, no association was observed between DM and oral precancerous lesions.
Liposomes in topical ophthalmic drug delivery: an update

Agarwal R, Iezhitsa I, Agarwal P, Abdul Nasir NA, Razali N, Alyautdin R, et al.

Drug Deliv, 2016 May;23(4):1075-91.
PMID: 25116511 DOI: 10.3109/10717544.2014.943336

Topical route of administration is the most commonly used method for the treatment of ophthalmic diseases. However, presence of several layers of permeation barriers starting from the tear film till the inner layers of cornea make it difficult to achieve the therapeutic concentrations in the target tissue within the eye. In order to circumvent these barriers and to provide sustained and targeted drug delivery, tremendous advances have been made in developing efficient and safe drug delivery systems. Liposomes due to their unique structure prove to be extremely beneficial drug carriers as they can entrap both the hydrophilic and hydrophobic drugs. The conventional liposomes had several drawbacks particularly their tendency to aggregate, the instability and leakage of entrapped drug and susceptibility to phagocytosis. Due to this reason, for a long time, liposomes as drug delivery systems did not attract much attention of researchers and clinicians. However, over recent years development of new generation liposomes has opened up new approaches for targeted and sustained drug delivery using liposomes and has rejuvenated the interest of researchers in this field. In this review we present a summary of current literature to understand the anatomical and physiological limitation in achieving adequate ocular bioavailability of topically applied drugs and utility of liposomes in overcoming these limitations. The recent developments related to new generation liposomes are discussed.
Fulltext Valorization of discarded face mask for bioactive compound synthesis and photodegradation of dye

Kiong TC, Nordin N, Ahmad Ruslan NAA, Kan SY, Ismail NM, Zakaria Z, et al.

Environ Res, 2022 Oct;213:113737.
PMID: 35752328 DOI: 10.1016/j.envres.2022.113737

To keep COVID-19 at bay, most countries have mandated the use of face masks in public places and imposed heavy penalties for those who fail to do so. This has inadvertently created a huge demand for disposable face masks and worsened the problem of littering, where a large number of used masks are constantly discarded into the environment. As such, an efficient and innovative waste management strategy for the discarded face mask is urgently needed. This study presents the transformation of discarded face mask into catalyst termed 'mask waste ash catalyst (MWAC)' to synthesise bisindolylmethanes (BIMs), alkaloids that possess antibacterial, antioxidant and antiviral properties. Using commercially available aldehydes and indole, an excellent yield of reaction (62-94%) was achieved using the MWAC in the presence of water as the sole solvent. On the other hand, the FT-IR spectrum of MWAC showed the absorption bands at 2337 cm-1, 1415 cm-1 and 871 cm-1, which correspond to the signals of calcium oxide. It is then proposed that the calcium oxides mainly present in MWAC can protonate oxygen atoms in the carbonyl molecule of the aldehyde group, thus facilitating the nucleophile attack by indole which consequently improved the product yield. Moreover, the MWAC is also observed to facilitate the photodegradation of methylene blue with an efficiency of up to 94.55%. Our results showed the potential applications of the MWAC derived from discarded face masks as a sustainable catalyst for bioactive compound synthesis and photodegradation of dye compounds.
Anterior and posterior segment changes in rat eyes with chronic steroid administration and their responsiveness to antiglaucoma drugs

Razali N, Agarwal R, Agarwal P, Kapitonova MY, Kannan Kutty M, Smirnov A, et al.

Eur J Pharmacol, 2015 Feb 15;749:73-80.
PMID: 25481859 DOI: 10.1016/j.ejphar.2014.11.029

Steroid-induced ocular hypertension (SIOH) is associated with topical and systemic use of steroids. However, SIOH-associated anterior and posterior segment morphological changes in rats have not been described widely. Here we describe the pattern of intraocular pressure (IOP) changes, quantitative assessment of trabecular meshwork (TM) and retinal morphological changes and changes in retinal redox status in response to chronic dexamethasone treatment in rats. We also evaluated the responsiveness of steroid-pretreated rat eyes to 5 different classes of antiglaucoma drugs that act by different mechanisms. Up to 80% of dexamethasone treated animals achieved significant and sustained IOP elevation. TM thickness was significantly increased and number of TM cells was significantly reduced in SIOH rats compared to the vehicle-treated rats. Quantitative assessment of retinal morphology showed significantly reduced thickness of ganglion cell layer (GCL) and inner retina (IR) in SIOH rats compared to vehicle-treated rats. Estimation of retinal antioxidants including catalase, superoxide dismutase and glutathione showed significantly increased retinal oxidative stress in SIOH animals. Furthermore, steroid-treated eyes showed significant IOP lowering in response to treatment with 5 different drug classes. This indicated the ability of SIOH eyes to respond to drugs acting by different mechanisms. In conclusion, SIOH was associated with significant morphological changes in TM and retina and retinal redox status. Additionally, SIOH eyes also showed IOP lowering in response to drugs that act by different mechanisms of action. Hence, SIOH rats appear to be an inexpensive and noninvasive model for studying the experimental antiglaucoma drugs for IOP lowering and neuroprotective effects.
IOP lowering effect of topical trans-resveratrol involves adenosine receptors and TGF-β2 signaling pathways

Razali N, Agarwal R, Agarwal P, Froemming GRA, Tripathy M, Ismail NM

Eur J Pharmacol, 2018 Nov 05;838:1-10.
PMID: 30171854 DOI: 10.1016/j.ejphar.2018.08.035

Trans-resveratrol was earlier shown to lower intraocular pressure (IOP) in rats; however, its mechanisms of action remain unclear. It has been shown to modulate adenosine receptor (AR) and TGF-β2 signaling, both of which play a role in regulating IOP. Hence, we investigated effects of trans-resveratrol on AR and TGF-β2 signaling. Steroid-induced ocular hypertensive (SIOH) rats were pretreated with A1AR, phospholipase C (PLC) and ERK1/2 inhibitors and were subsequently treated with single drop of trans-resveratrol. Metalloproteinases (MMP)-2 and -9 were measured in aqueous humor (AH). In another set of experiments, effect of trans-resveratrol on AH level of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) was determined after single and multiple drop administration in SIOH rats. Effect of trans-resveratrol on ARs expression, PLC and pERK1/2 activation and MMPs, tPA and uPA secretion was determined using human trabecular meshwork cells (HTMC). Further, effect of trans-resveratrol on TGF-β2 receptors, SMAD signaling molecules and uPA and tPA expression by HTMC was determined in the presence and absence of TGF-β2. Pretreatment with A1AR, PLC and ERK1/2 inhibitors antagonized the IOP lowering effect of trans-resveratrol and caused significant reduction in the AH level of MMP-2 in SIOH rats. Trans-resveratrol increased A1AR and A2AAR expression, cellular PLC, pERK1/2 levels and MMP-2, tPA and uPA secretion by HTMC. Additionally, it produced TGFβRI downregulation and SMAD 7 upregulation. In conclusion, IOP lowering effect of trans-resveratrol involves upregulation of A1AR expression, PLC and ERK1/2 activation and increased MMP-2 secretion. It downregulates TGFβRI and upregulates SMAD7 hence, inhibits TGF-β2 signaling.
Intraocular pressure-lowering effects of imidazo[1,2-a]- and pyrimido[1,2-a]benzimidazole compounds in rats with dexamethasone-induced ocular hypertension

Marcus AJ, Iezhitsa I, Agarwal R, Vassiliev P, Spasov A, Zhukovskaya O, et al.

Eur J Pharmacol, 2019 May 05;850:75-87.
PMID: 30716317 DOI: 10.1016/j.ejphar.2019.01.059

Ocular hypertension is believed to be involved in the etiology of primary open-angle glaucoma. Although many pharmaceutical agents have been shown to be effective for the reduction of intraocular pressure (IOP), a significant opportunity to improve glaucoma treatments remains. Thus, the aims of the present study were: (1) to evaluate the IOP-lowering effect of four compounds RU-551, RU-555, RU-839 (pyrimido[1,2-a]benzimidazole), and RU-615 (imidazo[1,2-a]benzimidazole) on steroid-induced ocular hypertension in rats after single drop and chronic applications; and (2) to test in silico and in vitro conventional rho-associated kinase (ROCK) inhibitory activity of the selected compound. This study demonstrated that RU-551, RU-555, RU-839, and RU-615 significantly reduced IOP in Sprague Dawley rats with dexamethasone (DEXA) induced ocular hypertension after single drop administration (0.1%), however RU-615 showed the best IOP lowering effect as indicated by maximum IOP reduction of 22.32% from baseline. Repeated dose topical application of RU-615 caused sustained reduction of IOP from baseline throughout the 3 weeks of treatment with maximum IOP reduction of 30.31% on day 15. This study also showed that the steroid-induced increase in IOP is associated with increased retinal oxidative stress and significant retinal ganglion cells (RGCs) loss. Prolonged treatment with RU-615 over 3 weeks results in normalization of IOP in DEXA-treated rats with partial restoration of retinal antioxidant status (catalase, glutathione and superoxide dismutase) and subsequent protective effect against RGC loss. Thus, IOP lowering activity of RU-615 together with antioxidant properties might be the factors that contribute to prevention of further RGC loss. In vitro part of this study explored the ROCK inhibitory activity of RU-615 using dexamethasone-treated human trabecular meshwork cells as a possible mechanism of action of its IOP lowering activity. However, this study didn't show conventional ROCK inhibition by RU-615 which was later confirmed by in silico consensus prediction. Therefore, in the future studies it is important to identify the upstream target receptors for RU-615 and then delineate the involved intracellular signalling pathways which are likely to be other than ROCK inhibition.
Topical trans-resveratrol ameliorates steroid-induced anterior and posterior segment changes in rats

Razali N, Agarwal R, Agarwal P, Tripathy M, Kapitonova MY, Kutty MK, et al.

Exp Eye Res, 2016 Feb;143:9-16.
PMID: 26424219 DOI: 10.1016/j.exer.2015.09.014

Steroid-induced hypertension and glaucoma is associated with increased extracellular meshwork (ECM) deposition in trabecular meshwork (TM). Previous studies have shown that single drop application of trans-resveratrol lowers IOP in steroid-induced ocular hypertensive (SIOH) rats. This IOP lowering is attributed to activation of adenosine A1 receptors, which may lead to increased matrix metalloproteinase (MMP)-2 activity. This study evaluated the effect of repeated topical application of trans-resveratrol for 21 days in SIOH animals on IOP, changes in MMP-2 level in aqueous humor, trabecular meshwork and retinal morphology and retinal redox status. We observed that treatment with trans-resveratrol results in significant and sustained IOP reduction in SIOH rats. This IOP reduction is associated with significantly higher aqueous humor total MMP-2 level; significantly reduced TM thickness and increased number of TM cells. Treatment with trans-resveratrol also significantly increased ganglion cell layer (GCL) thickness, the linear cell density in the GCL and inner retina thickness; and significantly reduced retinal oxidative stress compared to the SIOH vehicle-treated group. In conclusion, repeated dose topical application of trans-resveratrol produces sustained IOP lowering effect, which is associated with increased level of aqueous humor MMP-2, normalization of TM and retinal morphology and restoration of retinal redox status.
Magnesium acetyltaurate protects against endothelin-1 induced RGC loss by reducing neuroinflammation in Sprague dawley rats

Nor Arfuzir NN, Agarwal R, Iezhitsa I, Agarwal P, Ismail NM

Exp Eye Res, 2020 05;194:107996.
PMID: 32156652 DOI: 10.1016/j.exer.2020.107996

Endothelin-1 (ET-1), a potent vasoconstrictor, plays a significant role in the pathophysiology of ocular conditions like glaucoma. Glaucoma is characterized by apoptotic loss of retinal ganglion cells (RGCs) and loss of visual fields and is a leading cause of irreversible blindness. In glaucomatous eyes, retinal ischemia causes release of pro-inflammatory mediators such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α and promotes activation of transcription factors such as nuclear factor kappa B (NFKB) and c-Jun. Magnesium acetyltaurate (MgAT) has previously been shown to protect against ET-1 induced retinal and optic nerve damage. Current study investigated the mechanisms underlying these effects of MgAT, which so far remain unknown. Sprague dawley rats were intravitreally injected with ET-1 with or without pretreatment with MgAT. Seven days post-injection, retinal expression of IL-1β, IL-6, TNF-α, NFKB and c-Jun protein and genes was determined using multiplex assay, Western blot and PCR. Animals were subjected to retrograde labeling of RGCs to determine the extent of RGC survival. RGC survival was also examined using Brn3A staining. Furthermore, visual functions of rats were determined using Morris water maze. It was observed that pre-treatment with MgAT protects against ET-1 induced increase in the retinal expression of IL-1β, IL-6 and TNF-α proteins and genes. It also protected against ET-1 induced activation of NFKB and c-Jun. These effects of MgAT were associated with greater RGC survival and preservation of visual functions in rats. In conclusion, MgAT prevents ET-1 induced RGC loss and loss of visual functions by suppressing neuroinflammatory reaction in rat retinas.
Fulltext Protective effect of palm vitamin E and α-tocopherol against gastric lesions induced by water immersion restraint stress in Sprague-Dawley rats

Ibrahim IA, Yusof K, Ismail NM, Fahami NA

Indian J Pharmacol, 2008 Mar;40(2):73-7.
PMID: 21279170 DOI: 10.4103/0253-7613.41042

OBJECTIVE: Stress can lead to various changes in the gastrointestinal tract of rats. The present study was designed to compare the effect of palm vitamin E (PVE) and α-tocopherol (α-TF) supplementations on the gastric parameters important in maintaining gastric mucosal integrity in rats exposed to water immersion restraint stress (WRS). These parameters include gastric acidity, plasma gastrin level, gastric prostaglandin E(2) (PGE(2)), and gastric lesions.
MATERIALS AND METHODS: Sixty male Sprague-Dawley rats (200-250 g) were divided into three equal groups: a control group, which received a normal rat diet (RC), and two treatment groups, receiving oral supplementation of either PVE or α-TF at 60 mg/kg body weight for 28 days. Each group was further divided into two groups: the nonstress and stress groups. The stress groups were subjected to 3.5 h of WRS once at the end of the treatment period. Blood samples were then taken to measure the gastrin level, after which the rats were killed. Gastric juice was collected for measurement of gastric acidity and gastric tissue was taken for measurement of gastric mucosal lesions and PGE(2).
RESULTS: Exposure to stress resulted in the production of gastric lesions. PVE and α-TF lowered the lesion indices as compared to the stress control group. Stress reduced gastric acidity but pretreatment with PVE and α-TF prevented this reduction. The gastrin levels in the stress group were lower as compared to that in the nonstress control. However, following treatment with PVE and α-TF, gastrin levels increased and approached the normal level. There was also a significant reduction in the gastric PGE(2) content with stress exposure, but this reduction was blocked with treatment with both PVE and α-TF.
CONCLUSION: In conclusion, WRS leads to a reduction in the gastric acidity, gastrin level, and gastric PGE(2) level and there is increased formation of gastric lesions. Supplementation with either PVE or α-TF reduces the formation of gastric lesions, possibly by blocking the changes in the gastric acidity, gastrin, and gastric PGE(2) induced by stress. No significant difference between PVE and α-TF was observed.
Fulltext Integration of Islamic input in Medical Curriculum–Universiti Sains Islam Malaysia (USIM) experience

Jamilah J, Ahmad Najib A, Dzulkhairi MR, Ariff HO, Nasri Ismail NM

International Medical Journal Malaysia, 2014;13(2):73-77.
MyJurnal

Muslim doctors are those qualified doctors who practise their professional knowledge and skills in line with Islam and upholds the highest standards of ethical and professional behaviour. The medical curriculum of the Faculty of Medicine and Health Sciences of Universiti Sains Islam Malaysia (USIM) was designed with the integration of Islamic input which aims at producing doctors who are able to practise medicine that is integrated with Islamic, moral and ethical values. Halaqah Studies and Fundamental Islamic Knowledge (FIK) courses such as History of Medicine in Islam, Science and Medicine in Quran and Sunnah, Akhlak and Tasawuf, Islamic Jurisprudence and Medical Ethics and Fiqh Issues are taught to students during the pre-clinical and clinical phases. Memorization of selected Quranic verses throughout the programme aim to get the students to apply the verses of the al-Quran into practice in everyday life and especially in their clinical practice. Islamic values are emphasised during doctor-patient interactions in all clinical postings. Islamic knowledge and values integrated in the curriculum are assessed in written and clinical examinations. The outcome of the integration of the Naqli component in the medical curriculum has been demonstrated positively by the students in the patient management problems and clinical consultations. Studies on the outcome of the integrated Islamic input in the medical curriculum among the clinical students and graduates are being carried out.
Vitamin E and factors affecting atherosclerosis in rabbits fed a cholesterol-rich diet

Ismail NM, Abdul Ghafar N, Jaarin K, Khine JH, Top GM

Int J Food Sci Nutr, 2000;51 Suppl:S79-94.
PMID: 11271860

The present study aims to examine the effects of a palm-oil-derived vitamin E mixture containing tocotrienol (approximately 70%) and tocopherol (approximately 30%) on plasma lipids and on the formation of atherosclerotic plaques in rabbits given a 2% cholesterol diet. Eighteen New Zealand White rabbits (2.2-2.8 kg) were divided into three groups; group 1 (control) was fed a normal diet, group 2 (AT) was fed a 2% cholesterol diet and group 3 (PV) was fed a 2% cholesterol diet with oral palm vitamin E (60 mg/kg body weight) given daily for 10 weeks. There were no differences in the total cholesterol and triacylglycerol levels between the AT and PV groups. The PV group had a significantly higher concentrations of HDL-c and a lower TC/HDL-c ratio compared to the AT group (P < 0.003). The aortic tissue content of cholesterol and atherosclerotic lesions were comparable in both the AT and PV groups. However, the PV group had a lower content of plasma and aortic tissue malondialdehyde (P < 0.005). Our findings suggest that despite a highly atherogenic diet, palm vitamin E improved some important plasma lipid parameters, reduced lipid peroxidation but did not have an effect on the atherosclerotic plaque formation.
Dose-dependent effects of NMDA on retinal and optic nerve morphology in rats

Lambuk L, Jafri AJA, Iezhitsa I, Agarwal R, Bakar NS, Agarwal P, et al.

Int J Ophthalmol, 2019;12(5):746-753.
PMID: 31131232 DOI: 10.18240/ijo.2019.05.08

AIM: To investigate dose-dependent effects of N-methyl-D-aspartate (NMDA) on retinal and optic nerve morphology in rats.
METHODS: Sprague Dawley rats, 180-250 g in weight were divided into four groups. Groups 1, 2, 3 and 4 were intravitreally administered with vehicle and NMDA at the doses 80, 160 and 320 nmol respectively. Seven days after injection, rats were euthanized, and their eyes were taken for optic nerve toluidine blue and retinal hematoxylin and eosin stainings. The TUNEL assay was done for detecting apoptotic cells.
RESULTS: All groups treated with NMDA showed significantly reduced ganglion cell layer (GCL) thickness within inner retina, as compared to control group. Group NMDA 160 nmol showed a significantly greater GCL thickness than the group NMDA 320 nmol. Administration of NMDA also resulted in a dose-dependent decrease in the number of nuclei both per 100 µm GCL length and per 100 µm2 of GCL. Intravitreal NMDA injection caused dose-dependent damage to the optic nerve. The degeneration of nerve fibres with increased clearing of cytoplasm was observed more prominently as the NMDA dose increased. In accordance with the results of retinal morphometry analysis and optic nerve grading, TUNEL staining demonstrated NMDA-induced excitotoxic retinal injury in a dose-dependent manner.
CONCLUSION: Our results demonstrate dose-dependent effects of NMDA on retinal and optic nerve morphology in rats that may be attributed to differences in the severity of excitotoxicity and oxidative stress. Our results also suggest that care should be taken while making dose selections experimentally so that the choice might best uphold study objectives.

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