zaid Ibraheem | UPM - Academia.edu (original) (raw)

Papers by zaid Ibraheem

Malaria Research and Treatment, Nov 11, 2014

Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malari... more Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malaria in endemic areas. Antimalaria drugs act on different intracellular targets. The majority of them interfere with digestive vacuoles (DVs) while others affect other organelles, namely, apicoplast and mitochondria. Prevention of drug accumulation or access into the target site is one of the mechanisms that plasmodium adopts to develop resistance. Plasmodia are endowed with series of transporters that shuffle drugs away from the target site, namely, pf mdr (Plasmodium falciparum multidrug resistance transporter) and pf crt (Plasmodium falciparum chloroquine resistance transporter) which exist in DV membrane and are considered as putative markers of CQ resistance. They are homologues to human P-glycoproteins (P-gh or multidrug resistance system) and members of drug metabolite transporter (DMT) family, respectively. The former mediates drifting of xenobiotics towards the DV while the latter chucks them outside. Resistance to drugs whose target site of action is intravacuolar develops when the transporters expel them outside the DVs and vice versa for those whose target is extravacuolar. In this review, we are going to summarize the possible pf crt and pf mdr mutation and their role in changing plasmodium sensitivity to different anti-Plasmodium drugs.

Toxicological Research

Metabolic syndrome is one of the major risk factors that lead to various serious complications li... more Metabolic syndrome is one of the major risk factors that lead to various serious complications like cardiovascular abnormalities, hyperlipidemia and diabetes. Its coincidence with other organs dysfunction results in further deterioration of the condition or precipitation of other dysfunctions. This study aimed at studying the changes in the hepatic functions after the coincidence of the high fat or fructose diets induced metabolic syndrome along with the gentamicin induced nephrotoxicity. Briefly, six groups of male Sprague Daley rats (n = 10-12) were fed with different feeding protocols; viz; standard rodent's chow, an experimental high fat or high fructose diets feedings. For each, two groups were allocated that one of them was injected with normal saline and the other with 80 mg/kg/day I.P gentamicin during the last 24 days of the feeding period. The rats were monitored for changes in the metabolic data, glycemic control, lipid profile, renal and hepatic functions, oxidative stress and the inflammatory response. The study revealed stronger hepatic changes in the renal failure groups fed with the high fat diet rather than that in the groups fed with the high fructose diet. Although, the latter experienced a stronger deterioration in the glycemic control. The study suggests that the incidence of the hepatic changes is more linked to the incidence of the deterioration in the lipids profile that was observed after the high fat diet feeding. Overall, the coincidence of the high fat diet induced metabolic syndrome along with the renal failure constitutes a risk factor for the hepatic dysfunction.

Macromolecular Symposia, 2022

Background: The increasing incidence of drug resistance among various strains of Plasmodium falci... more Background: The increasing incidence of drug resistance among various strains of Plasmodium falciparum has compelled researchers to search for new improved therapeutic alternatives to current antimalarials. Consequently, the study aimed to investigate the effect of varying the duration of andrographolide exposure on its antiplasmodial effect against intra erythrocytic stages of the P. falciparum 3D7 parasite. Although andrographolide has demonstrated prior anti-plasmodial effect against P. falciparum 3D7, its time-dependent effect subsequent to different durations of drug exposure in addition to the impact of relevant pharmacologically active concentrations on the cellular morphology of various intraerythrocytic stages of the P. falciparum 3D7 parasite cycle are limited. Methods: P. falciparum 3D7 parasites cultivated in vitro in blood cultures were individually incubated with different concentrations of andrographolide, chloroquine and drug-free parasite culture which served as the representative control. Suppression of parasite growth was determined by parasite lactate dehydrogenase (pLDH) based drug sensitivity assay. The inhibition of parasite growth and changes in morphology of intraerythrocytic parasites subsequent to treatment initiation with andrographolide or chloroquine were assessed upon commencement of a synchronized cycle at 12, 24 and 48 h respectively. Results: Andrographolide showed satisfactory growth inhibitory effect however its inhibitory activity was substantially lower when compared to that of chloroquine. Unlike chloroquine which showed maximal inhibitory activity within the rst 12 h of the cycle, suppression of parasite growth by andrographolide was most prominent during the development of early trophozoites (viz the second 12 hours). Andrographolide failed to produce any effect on the morphology of ring stage parasites, it however produced a noticeable change in the morphological appearance and sizes of mature trophozoites. Whereas, with chloroquine notable changes to ring and trophozoite stages of the parasites were evident. Conclusion: The data obtained indicates the potential role of andrographolide as an adjunctive treatment in malaria subject to further clinical evaluations. malaria caused by P. vivax or P. ovale [5]. Both of the afcorementioned species have hepatic schizonts that may persist for long intervals of time intra-hepatically [6]. The discovery of novel antimalarial principles from plant sources in the past coupled with the emergence of drugresistance among species of P. falciparum to current antimalarials has prompted researchers to extensively explore phytochemicals as potential sources of anti-malarial pharmacophore candidates against antigenically variant malaria parasites as potential substitutes for the conventional anti-malarial drugs. Ethnomedicinal plants offer potential as a source of viable cost-effective anti-malarial principles in the realm of malaria chemotherapy particularly in underprivileged populations where access to healthcare facilities is limited. Andrographolide (AG) is a labdane diterpenoid derivative present abundantly in the herbaceous plant Andrograpcchis paniculata which is extensively cultivated in Southern Asia, China and some parts of Europe [7]. AG is an active principle of A. paniculate, and several publications have appeared in recent years highlighting the biological characteristics of AG including its antimicrobial, anti-in ammatory and antioxidant properties [8, 9]. The in vitro and in vivo anti-plasmodial activity of andrographolide was screened previously by Mishra et al., [10]. Additionally, Zaid et al., (2015) [11] reported the probable mechanism of action of AG as via permeation pathways channels visible on the membrane of infected RBCs as well as its impact on merozoite invasion. However, the impact of AG against different stages of the plasmodium parasite has not been su ciently explored. This study aimed to determine the time-dependent effect(s) of AG and CQ on the various stages of the P. falciparum 3D7 parasite's intraerythrocytic cycle (as a means to assess the stage of the parasite's reproductive cycle wherein maximum antiparasitic effect can be achieved) in addition to its impact on size and morphology of parasite forms (variants) constituting the intraerythrocytic cycle. Methods Red blood cells Uninfected RBCs (type O-negative) was donated by the rst author under the supervision of a haematologist. The blood was mixed with citrate phosphate buffer as anticoagulant (in the ratio of 1:9 anticoagulant/ blood); the blood was subsequently washed thrice using washing medium to remove plasma and white blood cells and resuspended to obtain a suspension of RBCs. The washing medium contained RPMI-1640, 25 mM HEPES (4-(2hydroxyethyl)-1-piperazine-ethan-sulphonic acid) buffer (pH 7.4), 24 mM sodium bicarbonate, 11 mM glucose and 50 µg/L gentamicin. The standard protocol for blood washing was adopted as previously described [12]. Chemicals and consumables Human O-erythrocytes were pelleted from blood suspended in RPMI-1640 medium.

Clinical and Experimental Pharmacology and Physiology, 2021

Clomiphene citrate (CC), letrozole and cetrorelix acetate are frequently used agents in controlle... more Clomiphene citrate (CC), letrozole and cetrorelix acetate are frequently used agents in controlled ovarian hyperstimulation (COH). However, these three agents have not yet been compared to one another regarding their pregnancy outcomes. The present study was designed to retrospectively compare pregnancy outcomes among the three aforementioned agents. This study involved infertile couples with an infertility duration of at least 2 years, ages 18 to 42 years and who were referred to have their first intrauterine insemination (IUI) treatment cycle. All patients underwent COH with recombinant follicle‐stimulating hormone (rFSH) plus CC (n = 118), letrozole (n = 81), or cetrorelix acetate (n = 62), followed by IUI. Using the one‐way multivariate analysis of covariance to control female patients’ ages, patients stimulated with cetrorelix acetate/rFSH or CC/rFSH had higher numbers of preovulatory follicles than women stimulated with letrozole/rFSH (P < .02), whereas women stimulated with cetrorelix acetate/rFSH had a thicker endometrium than women stimulated with CC/rFSH (P < .0005). Biochemical pregnancy rates were similar among the three protocols of COH. However, women stimulated with letrozole/rFSH showed clinical pregnancy rates higher than those stimulated with CC/rFSH (P = .003) or cetrorelix acetate/rFSH (P = .03) and subclinical abortion rates lower than those stimulated with CC/rFSH or cetrorelix acetate/rFSH (P = .009). Of the different protocols of COH, the odds of having a clinical pregnancy was 3.1 times greater for women stimulated with letrozole/rFSH than women stimulated with CC/rFSH (P = .004) and 2.8 times greater for women stimulated with letrozole/rFSH than women stimulated with cetrorelix acetate/rFSH (P = .03). Our observations show that increased numbers of preovulatory follicles or endometrium thickness do not necessarily improve pregnancy outcomes, because pregnancy outcomes are also subjected to the type of COH used agent. In this regard, letrozole produced fewer preovulatory follicles and did not significantly increase endometrium thickness, but significantly improved pregnancy outcomes in comparison to CC and cetrorelix acetate.

Purpose: To detect Strongyloides ratti in faecal samples using conventional methods and to confir... more Purpose: To detect Strongyloides ratti in faecal samples using conventional methods and to confirm the identification using a sensitive and specific method, namely, polymerase chain reaction (PCR). Methods: A PCR method targeting the small subunit of the rRNA gene was performed in this study for the detection of DNA from Strongyloides ratti (an animal model of S. stercoralis) in faecal samples of wild Brown rats, Rattus norvegicus. Results: Strongyloides ratti was detected in 34.2 % of collected rats by different conventional techniques and confirmed by PCR. The essay presented 100 % sensitivity with Strongyloides universal primer. Conclusion: The findings of this study suggest that the application of PCR with universal primer is a very sensitive methodology to detect S. ratti in faecal material of wild rats infected even with very low parasite burden.

Copyright © 2014 Zaid O. Ibraheem et al. This is an open access article distributed under the Cre... more Copyright © 2014 Zaid O. Ibraheem et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The current study evaluates the impact of high fructose feeding in ratmodel of gentamicin induced nephrotoxicity. Sprague-Dawley rats weighing 180–200 g were randomized into four groups; (C) received standard rodents chow with free access to ad libitum drinking water for 8 weeks and was considered as control, (F) received standard rodents chow with free access to drinking water supplemented with 20 % (W/V) fructose for the same abovementioned period, (FG) was fed as group F and was given 80mg/kg (bodyweight)/day gentamicin sulphate intraperitoneally during the last 20 days of the feeding period, and (G)was given gentamicin as above and fed as group C. Renal function was assessed at the end of the treatment period through measuring ...

AHMAD H. IBRAHIM1, KHAIRUL ANNUAR ZIT2, SAWSAN S. AL-RAWI3, MOHAMED B KHADEER AHAMED1 AND AMIN MA... more AHMAD H. IBRAHIM1, KHAIRUL ANNUAR ZIT2, SAWSAN S. AL-RAWI3, MOHAMED B KHADEER AHAMED1 AND AMIN MALIK SHAH ABDUL MAJID1 1Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM Pulau Pinang, Malaysia 2Genomelife Sdn. Bhd. (709881-A), E-2 Blok E, Excella Business Park, Jalan Ampang Putra, Taman Ampang Hilir, 55100 Kuala Lumpur, Malaysia 3Department of Environmental Technology, School of Industrial Technology, Universiti Sains Malaysia, 11800 USM Pulau Pinang, Malaysia

Materials Today: Proceedings, 2021

Pharmacognosy Magazine, 2020

In vitro antiplasmodium and chloroquine resistance reversal effects of mangostin ABSTRACT Aim/Bac... more In vitro antiplasmodium and chloroquine resistance reversal effects of mangostin ABSTRACT Aim/Background: Chloroquine (CQ) resistance that appeared among different strains of Plasmodium falciparum is considered as the worst catastrophe in the realm of malaria chemotherapy. CQ is still the most favorable drug among other antimalarials especially in the poor endemic areas due to its high potency and cost-effectiveness. This urged the scientists to explore for other alternatives or sensitizers for CQ. Materials and Methods: In this experiment, the antiplasmodium and the CQ resistance reversing effects of mangostin were tested using the in vitro SYBRE green-1-based drug sensitivity assay and the isobologram technique, respectively. Furthermore, its safety level toward two types of mammalian cells, namely Vero cells and red blood cells (RBCs), was screened using the 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide-based drug sensitivity and the RBCs hemolysis assays, respectively. On the other hand, its effect against hemozoin formation was screened using βhematin formation. Meanwhile, its molecular characters were determined the in silico on-line free chemi-informatic Molinspiration software for the molecular characterization as well as the standard testes for the measurement of the antioxidant effect. Results: Mangostin was moderately effective and selective toward the plasmodium so it is unsuitable to be a substituent for CQ. But it improved the sensitivity of the parasite to CQ. The molecular elucidation suggests that its CQ resistance reversal effect can be ascribed to its ability to interfere with hemozoin formation or the intravacuolar accumulation of CQ. Conclusion: Overall, the study suggests mangostin as a possible pharmacophore to develop new CQ resistance reversing agents but further studies are recommended to confirm this notion.

Annals of Tropical Medicine and Public Health, 2020

Strongyloides stercoralis is the intestinal nematode in humans, and it infects millions of people... more Strongyloides stercoralis is the intestinal nematode in humans, and it infects millions of people worldwide but thrives in warm countries with poor sanitation conditions. Clinical manifestations of the infection may range from asymptomatic to chronic. Strongyloides cause hyperinfection syndrome and dissemination in individuals with impaired cell-mediated immunity due to its ability to proliferate within the host that may increase the mortality rate up to 87%. The diagnosis of hyperinfection syndrome is difficult to establish and entails a high level of suspicion. The objective of the present study was to measure the expression level of C-type lectin gene coding to protein biomarker candidates from the excretory/secretory (ES) products of the infective filariform larva that can be used as diagnostic indicators for early hyperinfection syndrome in strongyloidiasis. An experimental study was carried out to induce hyperinfection of L3 larvae of S. ratti in experimentally immunosuppressed Wistar rats using prednisolone, a corticosteroid immunosuppressive drug. Prednisolone treatment resulted in a significant increase in the parasitic intensities. Relative semi-quantitative real-time PCR was performed to compare the expression level of the C-type lectin's gene between treated and nontreated groups with this drug. C-type lectin gene showed significantly higher expression levels in the treated samples. The study concluded that C-type lectin expression level was successfully measured and could be used as a diagnostic biomarker during early hyperinfection syndrome in strongyloidiasis.

Malaria Journal, 2019

Background The immune modulating potential of IL-35 in multiple human disorders has been reported... more Background The immune modulating potential of IL-35 in multiple human disorders has been reported. Consequent upon the recognition of inflammatory cytokine activation and its preponderance for mediating pathology during malaria infection, the study aimed to characterize the expression and functional contribution(s) of IL-35 in Plasmodium berghei (strain ANKA) infected mice. Methods Plasmodium berghei infection in male ICR mice was used as the rodent model of choice. The time course of IL-35 expression in the systemic circulation and tissues of P. berghei infected mice as well as their healthy control counterparts was assessed by enzyme linked immunosorbent assay and immunohistochemistry respectively. The effect of modulating IL-35 by recombinant IL-35 protein or neutralizing anti-Epstein-Barr virus-induced gene 3 antibody on the cytokine environment during P. berghei infection was assessed by flow cytometry. Furthermore, the influence of modulating IL-35 on histopathological hallmar...

Evidence-Based Complementary and Alternative Medicine, 2019

The emergence of drug-resistant strains of Plasmodium falciparum is the worst catastrophe that ha... more The emergence of drug-resistant strains of Plasmodium falciparum is the worst catastrophe that has ever confronted the dedicated efforts to eradicate malaria. This urged for searching other alternatives or sensitizers that reverse chloroquine resistance. In this experiment, the potential of andrographolide to inhibit plasmodial growth and reverse CQ resistance was tested in vitro using the SYBRE green-1-based drug sensitivity assay and isobologram technique, respectively. Its safety level toward mammalian cells was screened as well against Vero cells and RBCs using MTT-based drug sensitivity and RBC hemolysis assays, respectively. Its effect against hemozoin formation was screened using β-hematin formation and heme fractionation assays. Its molecular characters were determined using the conventional tests for the antioxidant effect measurement and the in silico molecular characterization using the online free chemi-informatic Molinspiration software. Results showed that andrographol...

Mesopotamia Journal of Agriculture, 2008

Journal of Parasitic Diseases, 2018

Triggering receptor expressed on myeloid cells 1 (TREM-1) is a potential molecular therapeutic ta... more Triggering receptor expressed on myeloid cells 1 (TREM-1) is a potential molecular therapeutic target for various inflammatory diseases. Despite that, the role of TREM-1 during malaria pathogenesis remains obscure with present literature suggesting a link between TREM-1 with severe malaria development. Therefore, this study aims to investigate the role of TREM-1 and TREM-1 related drugs during severe malaria infection in Plasmodium bergheiinfected mice model. Our findings revealed that TREM-1 concentration was significantly increased throughout the infection periods and TREM-1 was positively correlated with malaria parasitemia development. This suggests a positive involvement of TREM-1 in severe malaria development. Meanwhile, blocking of TREM-1 activation using rmTREM-1/Fc and TREM-1 clearance by mTREM-1/Ab had significantly reduced malaria parasitemia and suppressed the production of pro-inflammatory cytokines (TNF-a, IL-6 and IFN-c) and anti-inflammatory cytokine (IL-10). Furthermore, histopathological analysis of TREM-1 related drug treatments, in particular rmTREM-1/Fc showed significant improvements in the histological conditions of major organs (kidneys, spleen, lungs, liver and brain) of Plasmodium berghei-infected mice. This study showed that modulation of TREM-1 released during malaria infection produces a positive outcome on malaria infection through inhibition of pro-inflammatory cytokines secretion and alleviation of histopathological conditions of affected organs. Nevertheless, further investigation on its optimal dosage and dose dependant study should be carried out to maximise its full potential as immunomodulatory or as an adjuvant in line with current antimalarial agents.

Mediators of inflammation, 2018

Interleukin-33 (IL-33) is an IL-1 family member, which exhibits both pro- and anti-inflammatory p... more Interleukin-33 (IL-33) is an IL-1 family member, which exhibits both pro- and anti-inflammatory properties solely based on the type of the disease itself. Generally, IL-33 is expressed by both endothelial and epithelial cells and mediates its function based on the interaction with various receptors, mainly with ST2 variants. IL-33 is a potent inducer for the Th2 immune response which includes defence mechanism in brain diseases. Thus, in this paper, we review the biological features of IL-33 and the critical roles of IL-33/ST2 pathway in selected neurological disorders including Alzheimer's disease, multiple sclerosis, and malaria infection to discuss the involvement of IL-33/ST2 pathway during these brain diseases and its potential as future immunotherapeutic agents or for intervention purposes.

$Research paper thumbnail of Cosmos caudatus extract/fractions reduce smooth muscle cells migration and invasion in vitro : A potential benefit of suppressing atherosclerosis$

Porto Biomedical Journal, 2017

Background: Cosmos caudatus Kunth is a medicinal herb used traditionally in Latin America and Sou... more Background: Cosmos caudatus Kunth is a medicinal herb used traditionally in Latin America and South East Asia to retard aging, rigidify bones and for several cardiovascular uses. Objective: Is to assess C. caudatus extract/fractions' antioxidant and vascular smooth muscle cells (VSMC) migration and invasion inhibition capacity in vitro. Methods: Cosmos caudatus shoots were extracted by cold maceration in 50% ethanol to produce crude (CEE), and then the extract was fractionated to butanol (Bu.F), and aqueous fractions (Aq.f). Phenolics and saponins were quantified in extract and fractions by colorimetric methods and their antioxidant capacity was assayed in four different tests. Cytotoxic effect and safety level concentrations were determined for the fractions by using MTT assay. Migration and invasion inhibitory potential were measured in vitro at three different concentrations equivalent to (IC 10 , IC 25 , and IC 50). Finally, invasion inhibitory index was calculated to obtain the best fraction(s) that show(s) the highest ratio of cell invasion inhibition to the total cell migration inhibition. Results: Butanol fraction yield was the lowest; nevertheless, its phytochemical contents, antioxidant activities as well as its potency were the highest. Unlike other fractions, Bu.F was strongly correlated with all antioxidant assays experimented. In addition, it has the highest inhibitory effect at IC 25 against VSMCs migration and invasion that accounts for 53.93% and 59.94% respectively. Unexpectedly, Bu.F and CEE at IC 10 displayed the highest invasion inhibitory index (approx. 68%). Conclusion: Butanol fraction of C. caudatus offers a potentiality for the discovery of new leads for preventing atherosclerosis.