MyMedR

Displaying all 13 publications

Abstract:

Sort:

Fulltext Role of Different Pfcrt and Pfmdr-1 Mutations in Conferring Resistance to Antimalaria Drugs in Plasmodium falciparum

Ibraheem ZO, Abd Majid R, Noor SM, Sedik HM, Basir R

Malar Res Treat, 2014;2014:950424.
PMID: 25506039 DOI: 10.1155/2014/950424

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, pfmdr (Plasmodium falciparum multidrug resistance transporter) and pfcrt (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 pfcrt and pfmdr mutation and their role in changing plasmodium sensitivity to different anti-Plasmodium drugs.
Fulltext Impact of gentamicin coadministration along with high fructose feeding on progression of renal failure and metabolic syndrome in Sprague-Dawley rats

Ibraheem ZO, Basir R, Aljobory AKh, Ibrahim OE, Alsumaidaee A, Yam MF

Biomed Res Int, 2014;2014:823879.
PMID: 25045706 DOI: 10.1155/2014/823879

The current study evaluates the impact of high fructose feeding in rat model 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 80 mg/kg (body weight)/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 serum creatinine, uric acid and albumin, creatinine clearance, absolute and fractional excretion of both sodium and potassium, twenty-four-hour urinary excretion of albumin, and renal histology. For metabolic syndrome assessment, fasting plasma glucose and insulin were measured and oral glucose tolerance test was performed throughout the treatment period. Results showed that gentamicin enhances progression of fructose induced metabolic syndrome. On the other hand, fructose pretreatment before gentamicin injection produced a comparable degree of renal dysfunction to those which were given fructose-free water but the picture of nephrotoxicity was somewhat altered as it was characterized by higher extent of glomerular congestion and protein urea. Overall, more vigilance is required when nephrotoxic drugs are prescribed for patients with fructose induced metabolic syndrome.
Effect of high saturated free fatty acids feeding on progression of renal failure in rat model of experimental nephrotoxicity

Ibraheem ZO, Sattar MA, Abdullah NA, Rathore HA, Johns EJ

Bosn J Basic Med Sci, 2012 Feb;12(1):26-32.
PMID: 22364300

The current study evaluates the impact of high saturated fat feeding in rat model of experimental nephrotoxicity induced by gentamicin. Sprague-Dawley rats weighing 200 g were randomized into four groups; the first one received the standard rodents chow for 8 weeks and was treated as control, the second group (HFD)received an experimental high fat diet rich in palm kernel oil (40% of Calories as fat) for the same period. The third group (HFDG) was given 80 mg/kg (body weight)/day gentamicin sulphate intraperitoneally during the last 24 days of the feeding period while the fourth group was given gentamicin as above along with the standard rodents chow. Renal function was assessed through measuring serum creatinine, creatinine clearance and absolute and fractional excretion of both sodium and potassium. At the end, rats underwent a surgical procedure for blood pressure measurement. Renal function study showed a stronger nephrotoxicity for HFDG group. Hypertension was observed in HFD group while the pressure declined after gentamicin co-administration. Overall, changing the feeding behavior toward using more SAFFAs for rats injected with gentamicin promotes the progression of renal failure.
Orthosiphon stamineus: traditional uses, phytochemistry, pharmacology, and toxicology

Ameer OZ, Salman IM, Asmawi MZ, Ibraheem ZO, Yam MF

J Med Food, 2012 Aug;15(8):678-90.
PMID: 22846075 DOI: 10.1089/jmf.2011.1973

Orthosiphon stamineus Benth. (Lambiaceae) is an important plant in traditional folk medicine. This review is a comprehensive summary of the currently available chemical, pharmacological, and toxicological investigations as well as the traditional and therapeutic uses of this plant. Different in vitro and in vivo models have been addressed along with a survey of all phytochemicals identified in this plant, including flavonoids, terpenoids, and essential oils. Previous studies revealed that O. stamineus possesses several pharmacological activities, which are attributed to its phytochemical content. It was found that O. stamineus exhibits diuretic, hypouricemic, renal protective, antioxidant, anti-inflammatory, hepatoprotective, gastroprotective, antihypertensive, antidiabetic, antihyperlipidemic, antimicrobial, and anorexic activities. In conclusion, O. stamineus has wide traditional and pharmacological uses in various pathophysiological conditions. Therefore, it is an attractive subject for further experimental and clinical investigations.
The Potential of β Carbolin Alkaloids to Hinder Growth and Reverse Chloroquine Resistance in Plasmodium falciparum

Ibraheem ZO, Abdul Majid R, Mohd Noor S, Mohd Sidek H, Basir R

Iran J Parasitol, 2015 Oct-Dec;10(4):577-83.
PMID: 26811724

Nowadays, scourge of malaria as a fatalistic disease has increased due to emergence of drug resistance and tolerance among different strains of Plasmodium falciparum. Emergence of chloroquine (CQ) resistance has worsened the calamity as CQ is still considered the most efficient, safe and cost effective drug among other antimalarials. This urged the scientists to search for other alternatives or sensitizers that may be able to augment CQ action and reverse its resistance.
Liver functions in combined models of the gentamicin induced nephrotoxicity and metabolic syndrome induced by high fat or fructose diets: a comparative study

Ibraheem ZO, Farhan SS, Al Sumaidaee A, Al Sufi L, Bashir A, Balwa A, et al.

Toxicol Res, 2021 Apr;37(2):221-235.
PMID: 33868979 DOI: 10.1007/s43188-020-00059-w

Metabolic syndrome is one of the major risk factors that lead to various serious complications like cardiovascular abnormalities, hyperlipidemia and diabetes. Its co-incidence 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 co-incidence 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 co-incidence of the high fat diet induced metabolic syndrome along with the renal failure constitutes a risk factor for the hepatic dysfunction.
Fulltext Cosmos caudatus extract/fractions reduce smooth muscle cells migration and invasion in vitro : A potential benefit of suppressing atherosclerosis

Moshawih S, Cheema MS, Ibraheem ZO, Tailan ND, Hakim MN

Porto Biomed J, 2017;2(6):293-300.
PMID: 32258785 DOI: 10.1016/j.pbj.2017.03.008

HIGHLIGHTS: Cosmos caudatus Ethanolic extract fractionation by n-butanol produced a phenolics-saponin rich fraction.Cosmos caudatus butanol fraction was the most potent in all antioxidant and MTT assays.High concentrations of all fractions increased cells migration and invasion in vitro.Butanol fraction intermediate concentration maximally inhibited VSMC migration and invasion.Mild concentrations of crude and butanol fractions showed the best invasion inhibition index.
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 (IC10, IC25, and IC50). 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 IC25 against VSMCs migration and invasion that accounts for 53.93% and 59.94% respectively. Unexpectedly, Bu.F and CEE at IC10 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.
Antioxidant and cardio protective effect of palm oil leaves extract (standardized ethanolic fraction) in rats' model of saturated fats induced metabolic disorders

Ibraheem ZO, Satar M, Abdullah NA, Rathore H, Tan YC, Uldin F, et al.

Pak J Pharm Sci, 2014 Jan;27(1):1-9.
PMID: 24374430

Recently, it is suggested to use POLE (palm oil leaf extract) as a nutraceutical health product in food industry due to its newly discovered content of polyphenols and antioxidant vitamins. In the experiment, the antioxidant and anti-lipid-peroxidation activities of the extract were confirmed using; DPPH (1-diphenyl-2-picryl-hydrazil) radical scavenging activity, ferric ion induced lipid peroxidation inhibition, reducing power and hydrogen peroxide scavenging activity assays. The cardio-protective activity was studied in vivo using a model of metabolic syndrome induced by high fat diet. Lipid profile, obesity indices, renal tubular handling of water and electrolytes, blood pressure and arterial stiffness were measured at the end of the treatment period. Sprague Dawley rats weighing 150-200 g were divided into six groups, viz; group C; was treated as a negative control and fed with standard rodents chow, group H; was treated as a positive control and fed with an experimental diet enriched with saturated free fatty acids for 8 weeks, groups HP0.5, HP1 and HP2 which were fed with 0.5,1 and 2 g/kg (body weight) /day of POLE orally during the last 24 days of the high fat diet feeding period and group P; fed with highest dose of POLE. Results revealed that POLE possesses a cardio-protective effect which is ascribed to its content of polyphenols.
RAGE modulatory effects on cytokines network and histopathological conditions in malarial mice

Chin VK, Chuah YK, Lee TY, Nordin N, Ibraheem ZO, Zakaria ZA, et al.

Exp Parasitol, 2020 Sep;216:107946.
PMID: 32622941 DOI: 10.1016/j.exppara.2020.107946

This study was aimed at investigating the involvement of Receptor for Advanced Glycation End Products (RAGE) during malaria infection and the effects of modulating RAGE on the inflammatory cytokines release and histopathological conditions of affected organs in malarial animal model. Plasmodium berghei (P. berghei) ANKA-infected ICR mice were treated with mRAGE/pAb and rmRAGE/Fc Chimera drugs from day 1 to day 4 post infection. Survival and parasitaemia levels were monitored daily. On day 5 post infection, mice were sacrificed, blood were drawn for cytokines analysis and major organs including kidney, spleen, liver, brain and lungs were extracted for histopathological analysis. RAGE levels were increased systemically during malaria infection. Positive correlation between RAGE plasma concentration and parasitaemia development was observed. Treatment with RAGE related drugs did not improve survival of malaria-infected mice. However, significant reduction on the parasitaemia levels were recorded. On the other hand, inhibition and neutralization of RAGE production during the infection significantly increased the plasma levels of interleukin (IL-4, IL-17A, IL-10 and IL-2) and reduced interferon (IFN)-γ secretion. Histopathological analysis revealed that all treated malarial mice showed a better outcome in histological assessment of affected organs (brain, liver, spleen, lungs and kidney). RAGE is involved in malaria pathogenesis and targeting RAGE could be beneficial in malaria infected host in which RAGE inhibition or neutralization increased the release of anti-inflammatory cytokines (IL-10 and IL-4) and reduce pro-inflammatory cytokine (IFNγ) which may help alleviate tissue injury and improve histopathological conditions of affected organs during the infection.
Fulltext TREM-1 modulation produces positive outcome on the histopathology and cytokines release profile of Plasmodium berghei-infected mice

Chin VK, Asyran AMY, Zakaria ZA, Abdullah WO, Chong PP, Nordin N, et al.

J Parasit Dis, 2019 Mar;43(1):139-153.
PMID: 30956457 DOI: 10.1007/s12639-018-1070-3

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 berghei-infected 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-α, IL-6 and IFN-γ) 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.
Fulltext In Vitro Antiplasmodium and Chloroquine Resistance Reversal Effects of Andrographolide

Ibraheem ZO, Majid RA, Sidek HM, Noor SM, Yam MF, Abd Rachman Isnadi MF, et al.

Evid Based Complement Alternat Med, 2019;2019:7967980.
PMID: 31915453 DOI: 10.1155/2019/7967980

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 andrographolide has a moderate antiplasmodium effect that does not entitle it to be a substituent for chloroquine. Furthermore, andrographolide ameliorated the sensitivity of the parasite to chloroquine. Besides, it showed an indirect inhibitory effect against hemozoin formation within the parasite and augmented the chloroquine-induced inhibition of hemozoin formation. The study suggests that its chloroquine resistance reversal effect may be due to inhibition of chloroquine accumulation or due to its impact on the biological activity of the parasite. Overall, this in vitro study is a clue for the reliability of andrographolide to be added with chloroquine for reversal of chloroquine resistance and tolerance, but further in vivo studies are recommended to confirm this notion. In spite of its prominent and safe in vitro and in vivo growth inhibitory effect and its in vitro chloroquine resistance reversing effect, it is inapplicable to implement it in malaria chemotherapy to substitute chloroquine or to reverse its resistance.
Fulltext Investigation of Andrographolide Effect on Non-Infected Red Blood Cells Using the 1H-NMR-Based Metabolomics Approach

Alapid AAI, Abd Majid R, Ibraheem ZO, Mediani A, Ismail IS, Unyah NZ, et al.

Metabolites, 2021 Jul 28;11(8).
PMID: 34436427 DOI: 10.3390/metabo11080486

Andrographolide (AG) has been shown to have several medicinal and pharmaceutical effects, such as antimicrobial, anti-inflammatory, antioxidant, anti-diabetic, and anti-malarial activities. Moreover, studies to assess the pharmacological effect of AG on the metabolic changes of uninfected red blood cells (uRBCs) have not yet been investigated. This study aims to evaluate the pharmacological effects of AG compared to chloroquine (CQ) on the metabolic variations of uRBCs in vitro using a proton nuclear magnetic resonance (1H-NMR)-based metabolomics approach coupled with multivariate data analysis (MVDA). Forty-one metabolites were successfully identified by 1H-NMR. The results of the unsupervised data analysis principal component analysis (PCA) showed ideal differentiation between AG and CQ. PC1 and PC2 accounted for 71.4% and 17.7% of the explained variation, respectively, with a total variance of 89.10%. Based on S-plot and VIP values, a total of 28 and 32 metabolites were identified as biomarkers in uRBCs-AG and uRBCs-CQ, respectively. In uRBCs treated with AG, ten metabolic pathways were determined to be disturbed, including riboflavin metabolism, d-glutamate and d-glutamine metabolism, phenylalanine metabolism, glutathione metabolism, proline and arginine metabolism, arginine biosynthesis, citrate cycle, glycolysis/gluconeogenesis, and pyruvate metabolism as well as alanine, aspartate, and glutamate metabolism. In contrast, in CQ-treated uRBCs, nine affected metabolic pathways were determined, which involved the same metabolic pathways for uRBCs-AG, except for glutathione metabolism. These findings suggest an evident relationship between AG and CQ associated with metabolic changes in intact RBCs after being exposed to the treatment. The metabolomics results could allow useful comprehensive insights into the underlying mechanism of the action of AG and CQ on red blood cells. Consequently, the 1H-NMR-based metabolomics approach was successfully utilized to identify the pharmacological effects of AG and CQ on the metabolic variations of uRBCs.
Fulltext IL35 modulation altered survival, cytokine environment and histopathological consequences during malaria infection in mice

Bello RO, Abdullah MA, Abd Majid R, Chin VK, Abd Rachman Isnadi MF, Ibraheem ZO, et al.

Malar J, 2019 Dec 19;18(1):434.
PMID: 31856836 DOI: 10.1186/s12936-019-3070-x

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 hallmarks of malaria and disease progression was evaluated.
RESULTS: Interleukin-35 was significantly up regulated in serum and tissues of P. berghei infected mice and correlated with parasitaemia. Neutralization of IL-35 significantly enhanced the release of IFN-γ, decreased the expression of IL-6 and decreased parasitaemia patency. Neutralization of IL-35 was also associated with a tendency towards increased survival as well as the absence of pathological features associated with malaria infection unlike recombinant IL-35 protein administration which sustained a normal course of infection and unfavourable malaria associated histological outcomes in P. berghei infected mice.
CONCLUSION: These results indicate the involvement of IL-35 in P. berghei induced malaria infection. IL-35 neutralization strategies may represent viable therapeutic modalities beneficial for the resolution of malaria infection.

Filters

Please provide feedback to Administrator ([email protected])

External Links