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Fulltext Evaluation of Chondroprotective Activity of Channa striatus in Rabbit Osteoarthritis Model

Abdul Kadir A, Abdul Kadir A, Abd Hamid R, Mat Jais AM, Omar J, Sadagatullah AN, et al.

Biomed Res Int, 2019;2019:6979585.
PMID: 31355276 DOI: 10.1155/2019/6979585

Objectives: The objective of the study is to evaluate the chondroprotective activity of Channa striatus (Channa) and glucosamine sulphate (glucosamine) on histomorphometric examinations, serum biomarker, and inflammatory mediators in experimental osteoarthritis (OA) rabbit model.
Design: Anterior cruciate ligament transection (ACLT) was performed to induce OA in thirty-three male New Zealand white rabbits and were randomly divided into three groups: Channa, glucosamine, and control group. The control group received drinking water and the Channa and glucosamine groups were orally administered with 51.4 mg/kg of Channa extract and 77.5 mg/kg of glucosamine sulphate in drinking water, respectively, for eight weeks and then sacrificed. The articular cartilage was evaluated macroscopically and histologically using semiquantitative and quantitative methods. Serum cartilage oligomeric matric protein (COMP), cyclooxygenase 2 (COX-2) enzyme, and prostaglandin E2 (PGE2) were also determined.
Results: Macroscopic analysis revealed that Channa group have a significantly lower severity grade of total macroscopic score compared to the control (p < 0.001) and glucosamine (p < 0.05) groups. Semiquantitative histology scoring showed that both Channa and glucosamine groups had lower severity grading of total histology score compared to the control group (p < 0.001). In comparison with the control, Channa group had lower histopathological changes in three compartments of the joint compared to glucosamine group which had lower histological scoring in two compartments only. The cartilage thickness, area, and roughness of both Channa (p < 0.05) and glucosamine (p < 0.05) groups were superior compared to the control group. However, the Channa group demonstrated significantly less cartilage roughness compared to the glucosamine group (p < 0.05). Serum COMP levels were lower in both Channa (p < 0.05) and glucosamine (p < 0.05) groups compared to the control group.
Conclusion: Both oral administration of Channa extract and glucosamine exhibited chondroprotective action on an ACLT OA-induced rabbit model. However, Channa was superior to glucosamine in maintaining the structure of the cartilage.
Fulltext Tualang honey and DHA-rich fish oil reduce the production of pro-inflammatory cytokines in the rat brain following exposure to chronic stress

Asari MA, Zulkaflee MH, Sirajudeen KNS, Mohd Yusof NA, Mohd Sairazi NS

J Taibah Univ Med Sci, 2019 Aug;14(4):317-323.
PMID: 31488962 DOI: 10.1016/j.jtumed.2019.06.004

Objectives: The aim of the present study was to investigate the effects of Tualang honey (TH), DHA-rich fish oil, and their combination on the concentrations of selected pro-inflammatory cytokines in rat brains following exposure to chronic stress.
Methods: Fifty male Sprague-Dawley rats were divided into (i) control, (ii) stress-exposed, (iii) stress-exposed and treated with TH (1 g/kg body weight twice daily via oral gavage), (iv) stress-exposed and treated with DHA-rich fish oil (450 mg/kg body weight twice daily via oral gavage), and (v) stress-exposed and treated with a combination of TH and DHA-rich fish oil. The chronic stress regimen consisted of a combination of restraint stress and a swim stress test for 28 days. The concentrations of selected pro-inflammatory cytokines in brain homogenates (TNF-α, IL6, and IFN-γ) were measured by ELISA.
Results: The concentrations of TNF-α, IL6, and IFN-γ in brain homogenates from the DHA, TH, and TH + DHA-treated groups were significantly lower compared to the control and stress-only-exposed groups (p
Fulltext Sulfated glycosaminoglycans from crown-of-thorns Acanthaster planci - extraction and quantification analysis

Bahrom NA, Sirajudeen K, Yip GW, Latiff AA, Ghazali FC

Food Sci Nutr, 2013 Jan;1(1):83-9.
PMID: 24804017 DOI: 10.1002/fsn3.10

In this article, the novel inventive steps for the extraction and quantification of sulfated glycosaminoglycan (GAG) from Acanthaster planci starfish, generally known as crown-of-thorns (COT), are reported. Starfish have been implicated with collagenous distributions within their body anatomy, thus making it a prima facie fact searching for the possibility that GAGs can be isolated from COT. In this study, total-, N-, and O-sulfated GAGs were extracted from three anatomical regions of the COT (integument, internal tissue, and coelomic fluid) and comparison was made. The result showed that body region of COT seemed to contain higher amount of sulfated GAGs as opposed to the arm region (55.79 ± 0.65 μg/mg was the highest amount in the body extracted from its coelomic fluid and 32.28 ± 3.14 μg/mg was the highest amount in the arm extracted from its internal tissue). COT's integument and coelomic fluid from its body region possessed the highest total of sulfated GAGs content with no significant difference (P
Fulltext Anti-inflammatory and antioxidant effects of Tualang honey in alkali injury on the eyes of rabbits: experimental animal study

Bashkaran K, Zunaina E, Bakiah S, Sulaiman SA, Sirajudeen K, Naik V

BMC Complement Altern Med, 2011;11:90.
PMID: 21982267 DOI: 10.1186/1472-6882-11-90

Alkali injury is one of the most devastating injuries to the eye. It results in permanent unilateral or bilateral visual impairment. Chemical eye injury is accompanied by an increase in the oxidative stress. Anti-inflammatory and antioxidant agents play a major role in the treatment of chemical eye injuries. The purpose of this study is to evaluate the anti-inflammatory (clinical and histopathological) and antioxidant effects of Tualang honey versus conventional treatment in alkali injury on the eyes of rabbits.
Fulltext Effect of the antihypertensive drug enalapril on oxidative stress markers and antioxidant enzymes in kidney of spontaneously hypertensive rat

Chandran G, Sirajudeen KN, Yusoff NS, Swamy M, Samarendra MS

Oxid Med Cell Longev, 2014;2014:608512.
PMID: 25254079 DOI: 10.1155/2014/608512

Oxidative stress has been suggested to play a role in hypertension and hypertension induced organ damage. This study examined the effect of enalapril, an antihypertensive drug, on oxidative stress markers and antioxidant enzymes in kidney of spontaneously hypertensive rat (SHR) and Nω -nitro-L-arginine methyl ester (L-NAME) administered SHR. Male rats were divided into four groups (SHR, SHR+enalapril, SHR+L-NAME, and SHR+enalapril+L-NAME). Enalapril (30 mg kg(-1) day(-1)) was administered from week 4 to week 28 and L-NAME (25 mg kg(-1) day(-1)) was administered from week 16 to week 28 in drinking water. Systolic blood pressure (SBP) was measured during the experimental period. At the end of experimental periods, rats were sacrificed; urine, blood, and kidneys were collected for the assessment of creatinine clearance, total protein, total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and catalase (CAT), as well as histopathological examination. Enalapril treatment significantly enhanced the renal TAS level (P < 0.001) and SOD activity (P < 0.001), reduced the TBARS levels (P < 0.001), and also prevented the renal dysfunction and histopathological changes. The results indicate that, besides its hypotensive and renoprotective effects, enalapril treatment also diminishes oxidative stress in the kidneys of both the SHR and SHR+L-NAME groups.
Hypoglycemic and antioxidant effects of honey supplementation in streptozotocin-induced diabetic rats

Erejuwa OO, Omotayo EO, Gurtu S, Sulaiman SA, Ab Wahab MS, Sirajudeen KN, et al.

Int J Vitam Nutr Res, 2010 Jan;80(1):74-82.
PMID: 20533247 DOI: 10.1024/0300-9831/a000008

Oxidative stress plays a crucial role in the development of diabetic complications. The aims of this study were to investigate whether honey could reduce hyperglycemia and ameliorate oxidative stress in kidneys of streptozotocin-induced diabetic rats.
Antioxidant protection of Malaysian tualang honey in pancreas of normal and streptozotocin-induced diabetic rats

Erejuwa OO, Sulaiman SA, Wahab MS, Sirajudeen KN, Salleh MS, Gurtu S

Ann Endocrinol (Paris), 2010 Sep;71(4):291-6.
PMID: 20398890 DOI: 10.1016/j.ando.2010.03.003

Glucotoxicity contributes to beta-cell dysfunction through oxidative stress. Our previous study demonstrated that tualang honey ameliorated renal oxidative stress and produced hypoglycemic effect in streptozotocin (STZ)-induced diabetic rats. This present study investigated the hypothesis that hypoglycemic effect of tualang honey might partly be due to protection of pancreas against oxidative stress. Diabetes was induced by a single dose of STZ (60 mg/kg; ip). Diabetic rats were randomly divided into two groups and administered distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). Similarly, two groups of non-diabetic rats received distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). The animals were treated orally for 28 days. At the end of the treatment period, the honey-treated diabetic rats had significantly (p<0.05) reduced blood glucose levels [8.8 (5.8)mmol/L; median (interquartile range)] compared with the diabetic control rats [17.9 (2.6)mmol/L]. The pancreas of diabetic control rats showed significantly increased levels of malondialdehyde (MDA) and up-regulation of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Catalase (CAT) activity was significantly reduced while glutathione-S-transferase (GST) and glutathione reductase (GR) activities remained unchanged in the pancreas of diabetic rats. Tualang honey significantly (p<0.05) reduced elevated MDA levels. Honey treatment also restored SOD and CAT activities. These results suggest that hypoglycemic effect of tualang honey might be attributed to its antioxidative effect on the pancreas.
LPS-induced Apoptosis is Partially Mediated by Hydrogen Sulphide in RAW 264.7 Murine Macrophages

George L, Ramasamy T, Sirajudeen K, Manickam V

Immunol Invest, 2019 Jul;48(5):451-465.
PMID: 30689461 DOI: 10.1080/08820139.2019.1566355

Lipopolysaccharide (LPS) induces apoptosis in murine macrophages through the autocrine secretion of tumor necrosis factor (TNF)-α and nitric oxide (NO). LPS-induced inflammation in murine macrophages is associated with hydrogen sulfide (H2S) production. In this present study, we reported the novel role of H2S in LPS-induced apoptosis and its underlying molecular mechanism specifically at late phases in murine macrophage cells. Stimulation of RAW 264.7 macrophages with LPS resulted in a time- and dose-dependent induction of apoptosis. We observed that the LPS-induced early apoptosis (associated with TNF-α secretion) in macrophages was not inhibited in the presence of H2S inhibitor (DL-propargylglycine), whereas early apoptosis was absent in the presence of TNF receptor antibody. Interestingly, LPS-induced late apoptosis paralleled with H2S production was reduced in the presence of H2S inhibitor but not with TNF receptor antibody. The late apoptotic events mediated by H2S and not the TNF-α induced early apoptosis correlated significantly with the induction of p53 and Bax expression in LPS-induced macrophages. Thus, it is possible that RAW 264.7 murine macrophages treated with LPS mediated early apoptosis through TNF-α and the late apoptotic events through the production of H2S.
Tualang honey has higher phenolic content and greater radical scavenging activity compared with other honey sources

Kishore RK, Halim AS, Syazana MS, Sirajudeen KN

Nutr Res, 2011 Apr;31(4):322-5.
PMID: 21530807 DOI: 10.1016/j.nutres.2011.03.001

Many chronic diseases are associated with increased oxidative stress caused by an imbalance between free-radical production and the antioxidant level. Antioxidants, which are abundant in natural honey, are free-radical scavengers that either reduce the formation of or neutralize free radicals. The composition and source of honey greatly dictates its biochemical properties. We performed a comparative analysis of the total phenolic content and antioxidant potential of common commercially available honeys along with Malaysian tualang honey. In vitro biochemical analysis of the phenolic content by the Folin-Ciocalteau method revealed a significantly elevated phenolic content (83.96 ± 4.53 mg gallic acid equivalents per 100 g) in tualang honey. In addition, the antioxidant capacity (53.06 ± 0.41 mg ascorbic acid equivalents per gram) of tualang honey was greater, as assessed by the phosphomolybdenum method, 2,2-diphenyl-1-picryl-hydrazyl assay, and ferric reducing/antioxidant power assay. Peroxynitrite and superoxide radical scavenging activity was determined by spectrophotometric analysis in different honey types. Our data suggest that the elevated free-radical scavenging and antioxidant activity observed in tualang honey is due to the increased level of phenolic compounds. In addition to its antibacterial, anticarcinogenic, and anti-inflammatory properties, our study highlights the favorable antioxidant properties of tualang honey, which may be important to human nutrition and health.
Effects of antenatal, postpartum and post-weaning melatonin supplementation on blood pressure and renal antioxidant enzyme activities in spontaneously hypertensive rats

Lee SK, Sirajudeen KN, Sundaram A, Zakaria R, Singh HJ

J Physiol Biochem, 2011 Jun;67(2):249-57.
PMID: 21210316 DOI: 10.1007/s13105-010-0070-2

Although melatonin lowers blood pressure in spontaneously hypertensive rats (SHR), its effect following antenatal and postpartum supplementation on the subsequent development of hypertension in SHR pups remains unknown. To investigate this, SHR dams were given melatonin in drinking water (10 mg/kg body weight/day) from day 1 of pregnancy until day 21 postpartum. After weaning, a group of male pups continued to receive melatonin till the age of 16 weeks (Mel-SHR), while no further melatonin was given to another group of male pups (Maternal-Mel-SHR). Controls received plain drinking water. Systolic blood pressure (SBP) was measured at 4, 6, 8, 12 and 16 weeks of age, after which the kidneys were collected for analysis of antioxidant enzyme profiles. SBP was significantly lower till the age of 8 weeks in Maternal-Mel-SHR and Mel-SHR than that in the controls, after which no significant difference was evident in SBP between the controls and Maternal-Mel-SHR. SBP in Mel-SHR was lower than that in controls and Maternal-Mel-SHR at 12 and 16 weeks of age. Renal glutathione peroxidase (GPx) and glutathione s-transferase (GST) activities, levels of total glutathione and relative GPx-1 protein were significantly higher in Mel-SHR. GPx protein was however significantly higher in Mel-SHR. No significant differences were evident between the three groups in the activities of superoxide dismutase, catalase and glutathione reductase. In conclusion, it appears that while antenatal and postpartum melatonin supplementation decreases the rate of rise in blood pressure in SHR offspring, it however does not alter the tendency of offspring of SHR to develop hypertension.
Glutathione system in young spontaneously hypertensive rats

Lee SK, Arunkumar S, Sirajudeen KN, Singh HJ

J Physiol Biochem, 2010 Dec;66(4):321-7.
PMID: 20680541 DOI: 10.1007/s13105-010-0038-2

Glutathione (GSH) forms a part of the antioxidant system that plays a vital role in preventing oxidative stress, and an imbalance in the oxidant/antioxidant system has been linked to the pathogenesis of hypertension. The aim of this study was to investigate the status of the GSH system in the kidney of spontaneously hypertensive rats (SHR). Components of the GSH system, including glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), and total GSH content, were measured in the kidneys of 4, 6, 8, 12, and 16 weeks old SHR and Wistar-Kyoto (WKY) rats. Systolic blood pressure of SHR was significantly higher from the age of 6 weeks onwards compared with age-matched WKY rats. GPx activity in the SHR was significantly lower from the age of 8 weeks onwards when compared to that in age-matched WKY rats. No significant differences were evident in the GPx-1 protein abundance, and its relative mRNA levels, GR, GST activity, and total GSH content between SHR and age-matched WKY rats. The lower GPx activity suggests of an impairment of the GSH system in the SHR, which might be due to an abnormality in its protein rather than non-availability of a cofactor. Its role in the development of hypertension in SHR however remains unclear.
Effect of cross-fostering on renal anti-oxidant/oxidant status and development of hypertension in spontaneously hypertensive rats

Lee SK, Sirajudeen KN, Sundaram A, Zakaria R, Singh HJ

Clin Exp Pharmacol Physiol, 2011 Dec;38(12):854-9.
PMID: 21973174 DOI: 10.1111/j.1440-1681.2011.05624.x

1. The hypotensive effect of cross-fostering in spontaneously hypertensive rats (SHR) is thought to involve adjustments in renal function. However, its association with renal anti-oxidant/oxidant balance during cross-fostering is not known. 2. The present study examined the effect of cross-fostering and in-fostering of 1-day-old offspring between SHR and Wistar-Kyoto (WKY) dams on renal anti-oxidant/oxidant status and systolic blood pressure (SBP). Renal anti-oxidant/oxidant status and SBP were determined in the offspring from 4-16 weeks of age. 3. Cross-fostered SHR had significantly lower SBP than in-fostered SHR at 6, 8 and 12 weeks, but not at 16 weeks (127 ± 1 vs 144 ± 2, 138 ± 1 vs 160 ± 1, 174 ± 2 vs 184 ± 2 and 199 ± 2 vs 194 ± 3 mmHg at 6, 8, 12 and 16 weeks, respectively). No differences in SBP were evident between cross-fostered and in-fostered WKY rats. There were no significant differences in levels of thiobarbituric acid-reactive substances (TBARS), protein carbonyl and total anti-oxidant status (TAS) or superoxide dismutase, catalase, glutathione peroxidase (GPx), glutathione S-transferase and glutathione reductase activity between cross-fostered and in-fostered SHR or WKY offspring. However, compared with WKY rats, catalase activity was higher at 6 and 16 weeks, TAS was higher at 16 weeks and GPx activity and TBARS were lower at 16 weeks in SHR. 4. It appears that cross-fostering of SHR offspring to WKY dams during the early postnatal period causes a transient delay in the rise in blood pressure in SHR and that this does not involve the renal anti-oxidant/oxidant system.
The effects of prenatal oxidative stress levels on infant adiposity development during the first year of life

Loy SL, Sirajudeen KN, Hamid Jan JM

J Dev Orig Health Dis, 2014 Apr;5(2):142-51.
PMID: 24847700 DOI: 10.1017/S204017441300055X

Although numerous studies have been conducted to examine the causal factors of childhood obesity, the implications of intrauterine oxidative stress on early postnatal adiposity development remain to be elucidated. The Universiti Sains Malaysia Birth Cohort Study aimed to investigate the effects of prenatal oxidative stress levels on the development of infant adiposity during the first year of life. This study was conducted on the healthy pregnant women aged 19-40 years, from April 2010 to December 2012 in Kelantan, Malaysia. Maternal blood samples were drawn in the second trimester to analyse for oxidative stress markers. Infant anthropometric measurements were taken at birth, 2, 6 and 12 months of age. A total of 153 pregnant women and full-term infants were included in the analysis. Statistical test was conducted by using multiple linear regression. Through the infant first year of life, as maternal DNA damage level in the second trimester increased, infant weights at birth (β=-0.122, P<0.001), 2 months (β=-0.120, P=0013), 6 months (β=-0.209, P=0.003) and 12 months of age (β=-0.241, P=0.006) decreased after adjusting for confounders. Similar results were noted when infant body mass index-for-age Z-scores and triceps skinfold-for-age Z-scores were used as the adiposity indicators. In conclusion, the present study shows a consistent inverse association between maternal DNA damage and infant adiposity during the first year of life. These infants with reduced growth and adiposity in early postnatal life may have a high tendency to experience catch-up growth during childhood, which could be strongly associated with later obesity.
Quantitative analysis of sulphated glycosaminoglycans content of Malaysian sea cucumber Stichopus hermanni and Stichopus vastus

Masre SF, Yip GW, Sirajudeen KN, Ghazali FC

Nat Prod Res, 2012;26(7):684-9.
PMID: 21859370 DOI: 10.1080/14786419.2010.545354

Stichopus hermanni and Stichopus vastus are sea cucumber species from the Stichopodidae family within the coastal waters of Malaysia. The integument of these invertebrates is hypothesised to contain abundant glycosaminoglycans (GAGs). GAGs are divided into non-sulphated and sulphated GAGs. Sulphated GAGs have various chemico-biological functions that are beneficial to humans. This study quantitatively analysed N-, O-sulphated and total sulphated GAG content from three different anatomical regions (integument, internal organs and coelomic fluid) of S. hermanni and S. vastus. The integument revealed the highest content of total, O- and N-sulphated GAGs, followed by the internal organs and the coelomic fluid for both species of sea cucumbers. The percentage division of O- and N-sulphated GAGs suggested that anatomical parts of both species showed higher levels of O-sulphated GAGs compared to N-sulphated GAGs. In conclusion, these findings indicate that the integument body wall of S. hermanni and S. vastus is a rich source of sulphated GAGs.
Effect of different doses of Malaysian honey on reproductive parameters in adult male rats

Mohamed M, Sulaiman SA, Jaafar H, Sirajudeen KN

Andrologia, 2012 May;44 Suppl 1:182-6.
PMID: 21592175 DOI: 10.1111/j.1439-0272.2010.01159.x

The aim of this study was to evaluate the effect of different doses of Malaysian honey on male reproductive parameters in adult rats. Thirty-two healthy adult male Sprague-Dawley rats were randomly divided into four groups (eight rats per group). Group 1 (control group) was given 0.5 ml of distilled water. Groups 2, 3 and 4 were given 0.2, 1.2 and 2.4 g kg(-1) body weight of honey respectively. The rats were treated orally by gavage once daily for 4 weeks. Honey did not significantly alter body and male reproductive organs weights. The rats in Group 3 which received honey at 1.2 g kg(-1) had significantly higher epididymal sperm count than those in Groups 1, 2 and 4. No significant differences were found for the percentage of abnormal sperm, elongated spermatid count, reproductive hormonal levels as well as the histology of the testis among the groups. In conclusion, Malaysian honey at a dose of 1.2 g kg(-1) daily significantly increased epididymal sperm count without affecting spermatid count and reproductive hormones. These findings might suggest that oral administration of honey at this dose for 4 weeks may enhance spermiogenesis in adult rats.
Studies on the antioxidant properties of Tualang honey of Malaysia

Mohamed M, Sirajudeen K, Swamy M, Yaacob NS, Sulaiman SA

Afr J Tradit Complement Altern Med, 2009 Oct 15;7(1):59-63.
PMID: 21304614

Honey has been used since ancient times for its nutritional as well as curative properties. Tualang honey is collected from wild honey bees' hives on Tualang trees found in the Malaysian rain forest. It has been used traditionally for the treatment of various diseases, where its therapeutic value has partly been related to its antioxidant properties. This study therefore assessed the colour intensity, total phenolic content, antioxidant activity and antiradical activity of gamma irradiated Tualang Honey. The colour intensity at ABS₄₅₀ was 489.5 ± 1.7 mAU, total phenolic content was 251.7 ± 7.9 mg (gallic acid) /Kg honey, total antioxidant activity by FRAP assay was 322.1 ± 9.7 (µM Fe(II)) and the antiradical activity by DPPH assay was 41.30 ± 0.78 (% inhibition). The data confirms that the antioxidant properties of gamma irradiated Tualang honey are similar to other types of honeys reported in the literature.
Fulltext Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases

Mohd Sairazi NS, Sirajudeen KNS

Evid Based Complement Alternat Med, 2020;2020:6565396.
PMID: 32148547 DOI: 10.1155/2020/6565396

In recent years, natural products, which originate from plants, animals, and fungi, together with their bioactive compounds have been intensively explored and studied for their therapeutic potentials for various diseases such as cardiovascular, diabetes, hypertension, reproductive, cancer, and neurodegenerative diseases. Neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis are characterized by the progressive dysfunction and loss of neuronal structure and function that resulted in the neuronal cell death. Since the multifactorial pathological mechanisms are associated with neurodegeneration, targeting multiple mechanisms of actions and neuroprotection approach, which involves preventing cell death and restoring the function to damaged neurons, could be promising strategies for the prevention and therapeutic of neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for the treatment of neurodegenerative diseases. This review focused on the therapeutic potential of natural products and their bioactive compounds to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.
Fulltext Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

Mohd Sairazi NS, Sirajudeen KN, Asari MA, Muzaimi M, Mummedy S, Sulaiman SA

Evid Based Complement Alternat Med, 2015;2015:972623.
PMID: 26793262 DOI: 10.1155/2015/972623

Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS). In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA). KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.
Fulltext Effect of Clonidine (an antihypertensive drug) treatment on oxidative stress markers in the heart of spontaneously hypertensive rats

Nik Yusoff NS, Mustapha Z, Govindasamy C, Sirajudeen KN

Oxid Med Cell Longev, 2013;2013:927214.
PMID: 23766863 DOI: 10.1155/2013/927214

Hypertension is a risk factor for several cardiovascular diseases and oxidative stress suggested to be involved in the pathophysiology. Antihypertensive drug Clonidine action in ameliorating oxidative stress was not well studied. Therefore, this study investigate the effect of Clonidine on oxidative stress markers and nitric oxide (NO) in SHR and nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME) administered SHR. Male rats were divided into four groups [SHR, SHR+Clonidine (SHR-C), SHR+L-NAME, SHR+Clonidine+L-NAME(SHRC+L-NAME)]. Rats (SHRC) were administered with Clonidine (0.5 mg kg(-1) day(-1)) from 4 weeks to 28 weeks in drinking water and L-NAME (25 mg kg(-1) day(-1)) from 16 weeks to 28 weeks to SHRC+L-NAME. Systolic blood pressure (SBP) was measured. At the end of 28 weeks, all rats were sacrificed and in their heart homogenate, oxidative stress parameters and NO was assessed. Clonidine treatment significantly enhanced the total antioxidant status (TAS) (P < 0.001) and reduced the thibarbituric acid reactive substances (TBARS) (P < 0.001) and protein carbonyl content (PCO) (P < 0.05). These data suggest that oxidative stress is involved in the hypertensive organ damage and Clonidine not only lowers the SBP but also ameliorated the oxidative stress in the heart of SHR and SHR+L-NAME.
The influence of selenium status on body composition, oxidative DNA damage and total antioxidant capacity in newly diagnosed type 2 diabetes mellitus: A case-control study

Othman FB, Mohamed HJBJ, Sirajudeen KNS, Noh MFBM, Rajab NF

J Trace Elem Med Biol, 2017 Sep;43:106-112.
PMID: 28065595 DOI: 10.1016/j.jtemb.2016.12.009

Selenium is involved in the complex system of defense against oxidative stress in diabetes through its biological function of selenoproteins and the antioxidant enzyme. A case-control study was carried out to determine the association of plasma selenium with oxidative stress and body composition status presented in Type 2 Diabetes Mellitus (T2DM) patient and healthy control. This study involved 82 newly diagnosed T2DM patients and 82 healthy controls. Plasma selenium status was determined with Graphite Furnace Atomic Absorption Spectrometry. Body Mass Index, total body fat and visceral fat was assessed for body composition using Body Composition Analyzer (TANITA). Oxidative DNA damage and total antioxidant capacity were determined for oxidative stress biomarker status. In age, gender and BMI adjustment, no significant difference of plasma selenium level between T2DM and healthy controls was observed. There was as a significant difference of Oxidative DNA damage and total antioxidant capacity between T2DM patients and healthy controls with tail DNA% 20.62 [95% CI: 19.71,21.49] (T2DM), 17.67 [95% CI: 16.87,18.56] (control); log tail moment 0.41[95% CI: 0.30,0.52] (T2DM), 0.41[95% CI: 0.30,0.52] (control); total antioxidant capacity 0.56 [95% CI: 0.54,0.58] (T2DM), 0.60 [95% CI: 0.57,0.62] (control). Waist circumference, BMI, visceral fat, body fat and oxidative DNA damage in the T2DM group were significantly lower in the first plasma selenium tertile (38.65-80.90μg/L) compared to the second (80.91-98.20μg/L) and the third selenium tertiles (98.21-158.20μg/L). A similar trend, but not statistically significant, was observed in the control group.

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