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Protective effect of honey against cigarette smoke induced-impaired sexual behavior and fertility of male rats

Mohamed M, Sulaiman SA, Sirajudeen KN

Toxicol Ind Health, 2013 Apr;29(3):264-71.
PMID: 22275383 DOI: 10.1177/0748233711432568

Cigarette smoking is associated with sexual dysfunction and impaired fertility in males. The aim of this study was to determine the potential protective effect of honey against the toxic effect of cigarette smoke (CS) on sexual behavior and fertility of male rats. Thirty-two adult Sprague-Dawley rats were randomly divided into four groups (8 rats/group) as control, honey (H), CS and H plus CS (H + CS) groups. Rats in control and CS groups received oral administration of distilled water daily while rats in H and H + CS groups received honey (1.2 g/kg body weight/day) by oral gavage. Rats in CS and H + CS groups were also exposed to CS for 8 min 3 times/day. From 10 to 13 weeks of treatment, each male rat was cohabited with 3 untreated female rats for sexual behavioral and reproductive performance studies. Honey significantly increased the percentages of rats achieving intromission and ejaculation as well as increased mating and fertility indexes of male rats exposed to CS. Thus, honey has a protective effect against CS-induced impaired sexual behavior and fertility in male rats.
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.
Nitric oxide (NO), citrulline-NO cycle enzymes, glutamine synthetase, and oxidative status in kainic acid-mediated excitotoxicity in rat brain

Swamy M, Sirajudeen KN, Chandran G

Drug Chem Toxicol, 2009;32(4):326-31.
PMID: 19793024 DOI: 10.1080/01480540903130641

Neuronal excitation, involving the excitatory glutamate receptors, is recognized as an important underlying mechanism in neurodegenerative disorders. To understand their role in excitotoxicity, the nitric oxide synthase (NOS), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), glutamine synthetase (GS), and arginase activities, along with the concentration of nitrate/nitrite, thiobarbituric acid-reactive substances (TBARS), and total antioxidant status (TAS), were estimated in the cerebral cortex, cerebellum, and brain stem of rats subjected to kainic acid-mediated excitotoxicity. The results of this study clearly demonstrated the increased production of NO by increased activity of NOS. The increased activities of AS and AL suggest the increased and effective recycling of citrulline to arginine in excitotoxicity, making NO production more effective and contributing to its toxic effects. The decreased activity of GS may favor the prolonged availability of glutamic acid, causing excitotoxicity, leading to neuronal damage. The increased formation of TBARS and decreased TAS indicate the presence of oxidative stress in excitotoxicity.
Propolis ameliorates tumor nerosis factor-α, nitric oxide levels, caspase-3 and nitric oxide synthase activities in kainic acid mediated excitotoxicity in rat brain

Swamy M, Suhaili D, Sirajudeen KN, Mustapha Z, Govindasamy C

Afr J Tradit Complement Altern Med, 2014;11(5):48-53.
PMID: 25395704

BACKGROUND: Increased nitric oxide (NO), neuronal inflammation and apoptosis have been proposed to be involved in excitotoxicity plays a part in many neurodegenerative diseases. To understand the neuro-protective effects of propolis, activities of Nitric oxide synthase (NOS) and caspase-3 along with NO and tumor necrosis factor-α (TNF-α) levels were studied in cerebral cortex (CC), cerebellum (CB) and brain stem (BS) in rats supplemented with propolis prior to excitotoxic injury with kainic acid (KA).
MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into four groups (n=6 rats per group) as Control, KA, Propolis and KA+Propolis. The control group and KA group have received vehicle and saline. Propolis group and propolis + KA group were orally administered with propolis (150 mg/kg body weight), five times every 12 hours. KA group and propolis +KA group were injected subcutaneously with kainic acid (15 mg/kg body weight) and were sacrificed after 2 hrs. CC, CB and BS were separated, homogenized and used for estimation of NOS, caspase-3, NO and TNF-α by commercial kits. Results were analyzed by one way ANOVA, reported as mean + SD (n=6 rats), and p<0.05 was considered statistically significant.
RESULTS: The concentration of NO, TNF-α, NOS and caspase-3 activity were increased significantly (p<0.001) in all the three brain regions tested in KA group compared to the control. Propolis supplementation significantly (p<0.001) prevented the increase in NOS, NO, TNF-α and caspase-3 due to KA.
CONCLUSION: Results of this study clearly demonstrated that the propolis supplementation attenuated the NOS, caspase-3 activities, NO, and TNF-α concentration and in KA mediated excitotoxicity. Hence propolis can be a possible potential protective agent against excitotoxicity and neurodegenerative disorders.
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.
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.
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.
Fulltext Antioxidant protective effect of honey in cigarette smoke-induced testicular damage in rats

Mohamed M, Sulaiman SA, Jaafar H, Sirajudeen KN

Int J Mol Sci, 2011;12(9):5508-21.
PMID: 22016605 DOI: 10.3390/ijms12095508

Cigarette smoke (CS) can cause testicular damage and we investigated the possible protective effect of honey against CS-induced testicular damage and oxidative stress in rats. CS exposure (8 min, 3 times daily) and honey supplementation (1.2 g/kg daily) were given for 13 weeks. Rats exposed to CS significantly had smaller seminiferous tubules diameter and epithelial height, lower Leydig cell count and increased percentage of tubules with germ cell loss. CS also produced increased lipid peroxidation (TBARS) and glutathione peroxidase (GPx) activity, as well as reduced total antioxidant status (TAS) and activities of superoxide dismutase (SOD) and catalase (CAT). However, supplementation of honey significantly reduced histological changes and TBARS level, increased TAS level, as well as significantly restored activities of GPx, SOD and CAT in rat testis. These findings may suggest that honey has a protective effect against damage and oxidative stress induced by CS in rat testis.
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.
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.
Fulltext The effects of Tualang honey on female reproductive organs, tibia bone and hormonal profile in ovariectomised rats--animal model for menopause

Zaid SS, Sulaiman SA, Sirajudeen KN, Othman NH

BMC Complement Altern Med, 2010;10:82.
PMID: 21194469 DOI: 10.1186/1472-6882-10-82

Honey is a highly nutritional natural product that has been widely used in folk medicine for a number of therapeutic purposes. We evaluated whether Malaysian Tualang honey (AgroMas, Malaysia) was effective in reducing menopausal syndrome in ovariectomised female rats; an animal model for menopause.
Adverse effects of melatonin on rat pups of Wistar-Kyoto dams receiving melatonin supplementation during pregnancy

Singh HJ, Keah LS, Kumar A, Sirajudeen KN

Exp. Toxicol. Pathol., 2012 Nov;64(7-8):751-2.
PMID: 21354772 DOI: 10.1016/j.etp.2011.01.011

This report documents an incidental finding during a study investigating the effects of melatonin supplementation on the development of blood pressure in SHR. Administration of 10 mg/kg/day of melatonin in drinking water during pregnancy to Wistar-Kyoto (WKY) dams caused a loss of more than 50% of the pups by the age of three weeks and 95% by the age of 6 weeks. There was no maternal morbidity or mortality in the two strains or death of any of the SHR pups. No obvious physical defects were present but mean body weight was lower in the surviving WKY rats when compared to that of melatonin supplemented SHR or non-supplemented WKY pups. The reason for the high mortality in WKY pups is uncertain and appears to be strain if not batch specific. There is a need for caution in its use, particularly during pregnancy, and clearly necessitates more detailed studies.
Amiodarone-induced phospholipidosis: an in vivo [14C]-acetate uptake study in rat

Sirajudeen KN, Gurumoorthy P, Devaraj H, Devaraj SN

Drug Chem Toxicol, 2002 Aug;25(3):247-54.
PMID: 12173246

Amiodarone (AD), a potent antiarrhythmic drug, is often associated with several adverse effects. It is shown to accumulate phospholipids in various tissues, and the impaired catabolism of phospholipids has been implicated in AD-induced phospholipidosis. The synthesis of phospholipids in tissues has not been dealt with. Hence, the incorporation of [14C]-acetate into phospholipids has been studied to understand the AD-induced phospholipidosis in lung and liver. A significant increase in lung and liver phospholipids was observed after 21 and 28 days of AD (175 mg/kg body weight/day) treatment. In the lung and liver, the incorporation of [14C]-acetate into all phospholipid fractions was elevated, while in the lung mitochondria phosphatidylcholine, phosphatidyl ethanolamine and the cardiolipin levels were significantly increased. The results indicate that, in addition to the impaired catabolism of phospholipid, AD treatment resulted in increased phospholipid synthesis.
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.
Upregulation of catalase and downregulation of glutathione peroxidase activity in the kidney precede the development of hypertension in pre-hypertensive SHR

Sundaram A, Siew Keah L, Sirajudeen KN, Singh HJ

Hypertens Res, 2013 Mar;36(3):213-8.
PMID: 23096233 DOI: 10.1038/hr.2012.163

Although oxidative stress has been implicated in the pathogenesis of hypertension in spontaneously hypertensive rats (SHRs), there is little information on the levels of primary antioxidant enzymes status (AOEs) in pre-hypertensive SHR. This study therefore determined the activities of primary AOEs and their mRNA levels, levels of hydrogen peroxide (H2O2), malondialdehyde (MDA) and total antioxidant status (TAS) in whole kidneys of SHR and age-matched Wistar-Kyoto (WKY) rats aged between 2 and 16 weeks. Compared with age-matched WKY rats, catalase (CAT) activity was significantly higher from the age of 2 weeks (P<0.001) and glutathione peroxide (GPx) activity was lower from the age of 3 weeks (P<0.001) in SHR. CAT mRNA levels were significantly higher in SHR aged 2, 4, 6 and 12 weeks. GPx mRNA levels were significantly lower in SHR at 8 and 12 weeks. Superoxide dismutase activity or its mRNA levels were not different between the two strains. H2O2 levels were significantly lower in SHR from the age of 8 weeks (P<0.01). TAS was significantly higher in SHR from the age of 3 weeks (P<0.05). MDA levels were only significantly higher at 16 weeks of age in the SHR (P<0.05). The data suggest that altered renal CAT and GPx mRNA expression and activity precede the development of hypertension in SHR. The raised CAT activity perhaps contributes to the higher TAS and lower H2O2 levels in SHR. In view of these findings, the precise role of oxidative stress in the pathogenesis of hypertension in SHR needs to be investigated further.
Effects of acute ammonia toxicity on nitric oxide (NO), citrulline-NO cycle enzymes, arginase and related metabolites in different regions of rat brain

Swamy M, Zakaria AZ, Govindasamy C, Sirajudeen KN, Nadiger HA

Neurosci Res, 2005 Oct;53(2):116-22.
PMID: 16009439

Nitric oxide (NO) is involved in many pathophysiological processes in the brain. NO is synthesized from arginine by nitric oxide synthase (NOS) enzymes. Citrulline formed as a by-product of the NOS reaction, can be recycled to arginine by successive actions of argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) via the citrulline-NO cycle. Hyperammonemia is known to cause poorly understood perturbations of the citrulline-NO cycle. To understand the role of citrulline-NO cycle in hyperammonemia, NOS, ASS, ASL and arginase activities, as well as nitrate/nitrite (NOx), arginine, ornithine, citrulline, glutamine, glutamate and GABA were estimated in cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of rats subjected to acute ammonia toxicity. NOx concentration and NOS activity were found to increase in all the regions of brain in acute ammonia toxicity. The activities of ASS and ASL showed an increasing trend whereas the arginase was not changed. The results of this study clearly demonstrated the increased formation of NO, suggesting the involvement of NO in the pathophysiology of acute ammonia toxicity. The increased activities of ASS and ASL suggest the increased and effective recycling of citrulline to arginine in acute ammonia toxicity, making NO production more effective and contributing to its toxic effects.
Restoration of glutamine synthetase activity, nitric oxide levels and amelioration of oxidative stress by propolis in kainic acid mediated excitotoxicity

Swamy M, Norlina W, Azman W, Suhaili D, Sirajudeen KN, Mustapha Z, et al.

Afr J Tradit Complement Altern Med, 2014;11(2):458-63.
PMID: 25435633

BACKGROUND: Propolis has been proposed to be protective on neurodegenerative disorders. To understand the neuroprotective effects of honeybee propolis, glutamine synthetase (GS) activity, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and total antioxidant status (TAS) were studied in different brain regions-cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of rats supplemented with propolis and subjected to kainic acid (KA) mediated excitotoxicity.
MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into four groups; Control group and KA group received vehicle and saline. Propolis group and propolis + KA group were orally administered with propolis (150mg/kg body weight), five times every 12 hours. KA group and propolis + KA group were injected subcutaneously with kainic acid (15mg/kg body weight) and were sacrificed after 2 hrs and CC, CB and BS were separated homogenized and used for estimation of GS activity, NO, TBARS, and TAS concentrations by colorimetric methods. Results were analyzed by one-way ANOVA, reported as mean + SD from 6 animals, and p<0.05 considered statistically significant.
RESULTS: NO was increased (p< 0.001) and GS activity was decreased (p< 0.001) in KA treated group compared to control group as well as propolis + KA treated group. TBARS was decreased and TAS was increased (p< 0.001) in propolis + KA treated group compared KA treated group.
CONCLUSION: This study clearly demonstrated the restoration of GS activity, NO levels and decreased oxidative stress by propolis in kainic acid mediated excitotoxicity. Hence the propolis can be a possible potential candidate (protective agent) against excitotoxicity and neurodegenerative disorders.
Fulltext Honey supplementation in spontaneously hypertensive rats elicits antihypertensive effect via amelioration of renal oxidative stress

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

Oxid Med Cell Longev, 2012;2012:374037.
PMID: 22315654 DOI: 10.1155/2012/374037

Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR.
Effect of melatonin supplementation and cross-fostering on renal glutathione system and development of hypertension in spontaneously hypertensive rats

Siew-Keah L, Sundaram A, Sirajudeen KN, Zakaria R, Singh HJ

J Physiol Biochem, 2014 Mar;70(1):73-9.
PMID: 23975651 DOI: 10.1007/s13105-013-0282-3

Antenatal and postnatal environments are hypothesised to influence the development of hypertension. This study investigates the synergistic effect of cross-fostering and melatonin supplementation on the development of hypertension and renal glutathione system in spontaneously hypertensive rats (SHR). In one experiment, 1-day-old male SHR pups were fostered to either SHR (shr-SHR) or Wistar-Kyoto rats, (shr-WKY). In a concurrent experiment, SHR dams were given melatonin in drinking water (10 mg/kg body weight) from day 1 of pregnancy. Immediately following delivery, 1-day-old male pups were fostered either to SHR (Mel-shr-SHR) or WKY (Mel-shr-WKY) dams receiving melatonin supplementation until weaning on day 21. Upon weaning, melatonin supplementation was continued to these pups until the age of 16 weeks. Systolic blood pressures (SBP) were recorded at the age of 4, 6, 8, 12 and 16 weeks. Renal antioxidant activities were measured. Mean SBP of shr-WKY, Mel-shr-SHR and Mel-shr-WKY was significantly lower than that in shr-SHR until the age of 8 weeks. At 12 and 16 weeks of age, mean SBP of Mel-shr-WKY was lower than those in non-treated shr-SHR and shr-WKY pups but was not significantly different from that in Mel-shr-SHR. Renal glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were significantly higher in Mel-shr-SHR and Mel-shr-WKY at 16 weeks of age. It appears that combination of cross-fostering and melatonin supplementation exerts no synergistic effect on delaying the rise in blood pressure in SHR. The elevated GPx and GST activities are likely to be due to the effect of melatonin supplementation.

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