Displaying publications 1 - 20 of 26 in total

Abstract:
Sort:
  1. Fulltext Insulin-Like Growth Factor-1 (IGF-1) Reduces ischemic changes and increases circulating angiogenic factors in experimentally - induced myocardial infarction in rats
    Lisa M, Haleagrahara N, Chakravarthi S
    Vascular cell, 2011;3(1):13.
    PMID: 21651821 DOI: 10.1186/2045-824X-3-13
    Coronary artery disease is a global health concern in the present day with limited therapies. Extensive efforts have been devoted to find molecular therapies to enhance perfusion and function of the ischemic myocardium. Aim of the present study was to look into the effects of insulin like growth factor -1 (IGF-1) on circulating angiogenic factors after myocardial ischemia in rats.
  2. Neuroprotective effect of Centella asiatica extract (CAE) on experimentally induced parkinsonism in aged Sprague-Dawley rats
    Haleagrahara N, Ponnusamy K
    J Toxicol Sci, 2010 Feb;35(1):41-7.
    PMID: 20118623
    Reactive oxygen species (ROS) play an important role in ageing and age-related neurodegenerative changes including Parkinson's disease (PD). PD is characterized by signs of major oxidative stress and mitochondrial damage in the pars compacta of the substantia nigra. Present study was designed to investigate whether the Centella asiatica extract (CAE) would prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in aged Sprague-Dawley rats. Adult, male Sprague-dawley rats of 300-350 g were divided into control, C. asiatica alone, MPTP alone (20 mg/kg, for 21 days) and MPTP with C. asiatica (300 mg/kg for 21 days) groups. Effect of aqueous extract of C. asiatica on oxidative biomarker levels in corpus striatum and hippocampus homogenate was examined. MPTP-challenged rats elicited a significant increase in lipid hydroperoxides (LPO) (p < 0.01), protein-carbonyl-content (PCC) (p < 0.01) and xanthine oxidase (XO) (p < 0.01) when compared with control rats. There was a significant decrease in total antioxidants (TA) (p < 0.001), superoxide dismutase (SOD) (p < 0.001), glutathione peroxidase (GPx) (p < 0.01) and catalase (CAT) (p < 0.001) levels with MPTP treatment. Supplementation of CAE reduced LPO and PCC and significantly increased (p < 0.01) TA and antioxidant enzyme levels (p < 0.01) in corpus striatum and hippocampus. These results show that administration of C. asiatica was effective in protecting the brain against neurodegenerative disorders such as Parkinsonism.
  3. Protective effect of Etlingera elatior (torch ginger) extract on lead acetate--induced hepatotoxicity in rats
    Haleagrahara N, Jackie T, Chakravarthi S, Rao M, Kulur A
    J Toxicol Sci, 2010 Oct;35(5):663-71.
    PMID: 20930461
    Lead is known to disrupt the biological systems by altering the molecular interactions, cell signaling, and cellular function. Exposure to even low levels of lead may have potential hazardous effects on brain, liver, kidneys and testes. The efficacy of Etlingera elatior (torch ginger) to protect hepatotoxicity induced by lead acetate was evaluated experimentally in male Sprague - Dawley rats. Rats were exposed to lead acetate in drinking water (500 ppm) for 21 days and the effects of concurrent treatment with extract of E. elatior on hepatic lipid hydroperoxides (LPO), protein carbonyl content (PCC), total antioxidants (TA), superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione S- Transferase (GST) levels and histopathological changes in liver were evaluated. There was a significant decrease in TA and other antioxidant enzymes (p < 0.05) and increase in LPO and PCC (p < 0.05) with lead acetate ingestion. Concurrent treatment with E. elatior extract significantly reduced the LPO and PCC (p < 0.05) in serum and increased the antioxidant enzyme levels (p < 0.05) in the liver. Significant histopathological changes were seen in hepatic tissue with chronic lead ingestion. Treatment with E. elatior significantly reduced these lead-induced changes in hepatic architecture. E. elatior has also reduced the blood lead levels (BLL). Thus, there has been extensive biochemical and structural alterations indicative of liver toxicity with exposure to lead and E. elatior treatment significantly reduced these oxidative damage. Our results suggest that E. elatior has a powerful antioxidant effect against lead-induced hepatotoxicity.
  4. Fulltext Protective Mechanisms of Flavonoids in Parkinson's Disease
    Magalingam KB, Radhakrishnan AK, Haleagrahara N
    Oxid Med Cell Longev, 2015;2015:314560.
    PMID: 26576219 DOI: 10.1155/2015/314560
    Parkinson's disease is a chronic, debilitating neurodegenerative movement disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta region in human midbrain. To date, oxidative stress is the well accepted concept in the etiology and progression of Parkinson's disease. Hence, the therapeutic agent is targeted against suppressing and alleviating the oxidative stress-induced cellular damage. Within the past decades, an explosion of research discoveries has reported on the protective mechanisms of flavonoids, which are plant-based polyphenols, in the treatment of neurodegenerative disease using both in vitro and in vivo models. In this paper, we have reviewed the literature on the neuroprotective mechanisms of flavonoids in protecting the dopaminergic neurons hence reducing the symptoms of this movement disorder. The mechanism reviewed includes effect of flavonoids in activation of endogenous antioxidant enzymes, suppressing the lipid peroxidation, inhibition of inflammatory mediators, flavonoids as a mitochondrial target therapy, and modulation of gene expression in neuronal cells.
  5. Tocotrienols protect differentiated SH-SY5Y human neuroblastoma cells against 6-hydroxydopamine-induced cytotoxicity by ameliorating dopamine biosynthesis and dopamine receptor D2 gene expression
    Magalingam KB, Somanath SD, Md S, Haleagrahara N, Fu JY, Selvaduray KR, et al.
    Nutr Res, 2022 Feb;98:27-40.
    PMID: 35065349 DOI: 10.1016/j.nutres.2021.09.003
    Oxidative stress is a critical factor that triggers a "domino" cascade of events leading to the degeneration of dopaminergic neurons in Parkinson disease. Tocotrienols (T3) have antioxidant effects and can protect neuronal cells against oxidative damage. In the present study, we investigated the neuroprotective effects of different forms of T3 (alpha, delta, gamma) or tocotrienol-rich fraction (TRF) against 6-hydroxydopamine (6-OHDA)-induced oxidative damage in differentiated SH-SY5Y human neural cells. Differentiating the SH-SY5Y cells with retinoic acid and a low-serum culture medium for 6 days allowed development of human dopamine-like neural cells. Subsequently, the differentiated SH-SY5Y neural cells were pretreated with different forms of T3 for 24 hours before these cells were exposed to 6-OHDA. The T3 analogues and TRF displayed neuroprotective effects (P < .05) via restoration of cell viability and activation of antioxidant enzymes (e.g., superoxide dismutase, catalase). Notably, TRF was highly efficient in scavenging reactive oxygen species and upregulating dopamine and tyrosine hydroxylase levels in the differentiated SH-SY5Y cells. Gamma-T3 exhibited the most potent effects in attenuating apoptosis, whereas alpha-T3 was most effective in preventing 6-OHDA-induced leakage of α-Synuclein. Delta-T3 displayed a noticeable effect in upregulating the dopamine receptor D2 gene expression compared with controls. These findings suggest T3 isoforms and TRF demonstrate significant neuroprotective effects in protecting differentiated neural cells against 6-OHDA-mediated oxidative stress.
  6. Fulltext Tocotrienols Ameliorate Neurodegeneration and Motor Deficits in the 6-OHDA-Induced Rat Model of Parkinsonism: Behavioural and Immunohistochemistry Analysis
    Kumari M, Ramdas P, Radhakrishnan AK, Kutty MK, Haleagrahara N
    Nutrients, 2021 May 10;13(5).
    PMID: 34068460 DOI: 10.3390/nu13051583
    Parkinson's disease (PD) is a debilitating neurodegenerative disease, which progresses over time, causing pathological depigmentation of the substantia nigra (SN) in the midbrain due to loss of dopaminergic neurons. Emerging studies revealed the promising effects of some nutrient compounds in reducing the risk of PD. One such nutrient compound that possess neuroprotective effects and prevents neurodegeneration is tocotrienol (T3), a vitamin E family member. In the present study, a single dose intracisternal injection of 250 µg 6-hydroxydopamine (6-OHDA) was used to induce parkinsonism in male Sprague Dawley (SD) rats. Forty-eight hours post injection, the SD rats were orally supplemented with alpha (α)- and gamma (γ)-T3 for 28 days. The neuroprotective effects of α- and γ-T3 were evaluated using behavioural studies and immunohistochemistry (IHC). The findings from this study revealed that supplementation of α- and γ-T3 was able to ameliorate the motor deficits induced by 6-OHDA and improve the neuronal functions by reducing inflammation, reversing the neuronal degradation, and preventing further reduction of dopaminergic neurons in the SN and striatum (STR) fibre density.
  7. Neuroprotective effect of bioflavonoid quercetin in 6-hydroxydopamine-induced oxidative stress biomarkers in the rat striatum
    Haleagrahara N, Siew CJ, Mitra NK, Kumari M
    Neurosci Lett, 2011 Aug 15;500(2):139-43.
    PMID: 21704673 DOI: 10.1016/j.neulet.2011.06.021
    An increasing large body of research on Parkinson's disease (PD) has focused on the understanding of the mechanisms behind the potential neuro protection offered by antioxidants and iron chelating agents. In this study, the protective effect of the bioflavonoid quercetin on 6-hydroxydopamine (6-OHDA)-induced model of PD was investigated. PD was induced by a single intracisternal injection of 6-hydroxydopamine (300μg) to male Sprague-Dawley rats. Quercetin treatment (30mg/kg body weight) over 14 consecutive days markedly increased the striatal dopamine and antioxidant enzyme levels compared with similar measurements in the group treated with 6-OHDA alone. There was a significant decrease in protein carbonyl content in the striatum compared with that of rats that did not receive quercetin. A significant increase in neuronal survivability was also found with quercetin treatment in rats administered 6-OHDA. In conclusion, treatment with quercetin defended against the oxidative stress in the striatum and reduced the dopaminergic neuronal loss in the rat model of PD.
  8. Potential protective effect of sunitinib after administration of diclofenac: biochemical and histopathological drug-drug interaction assessment in a mouse model
    Tan JR, Chakravarthi S, Judson JP, Haleagrahara N, Segarra I
    Naunyn Schmiedebergs Arch Pharmacol, 2013 Jul;386(7):619-33.
    PMID: 23552887 DOI: 10.1007/s00210-013-0861-4
    Sunitinib is a tyrosine kinase inhibitor for GIST and advanced renal cell carcinoma. Diclofenac is used in cancer pain management. Coadministration may mediate P450 toxicity. We evaluate their interaction, assessing biomarkers ALT, AST, BUN, creatinine, and histopathological changes in the liver, kidney, heart, brain, and spleen. ICR mice (male, n = 6 per group/dose) were administered saline (group A) or 30 mg/kg diclofenac ip (group B), or sunitinib po at 25, 50, 80, 100, 140 mg/kg (group C) or combination of diclofenac (30 mg/kg, ip) and sunitinib (25, 50, 80, 100, 140 mg/kg po). Diclofenac was administered 15 min before sunitinib, mice were euthanized 4 h post-sunitinib dose, and biomarkers and tissue histopathology were assessed. AST was 92.2 ± 8.0 U/L in group A and 159.7 ± 14.6 U/L in group B (p < 0.05); in group C, it the range was 105.1-152.6 U/L, and in group D, it was 156.0-209.5 U/L (p < 0.05). ALT was 48.9 ± 1.6 U/L (group A), 95.1 ± 4.5 U/L (p < 0.05) in group B, and 50.5-77.5 U/L in group C and 82.3-115.6 U/L after coadministration (p < 0.05). Renal function biomarker BUN was 16.3 ± 0.6 mg/dl (group A) and increased to 29.9 ± 2.6 mg/dl in group B (p < 0.05) and it the range was 19.1-33.3 mg/dl (p < 0.05) and 26.9-40.8 mg/dl in groups C and D, respectively. Creatinine was 5.9 pmol/ml in group A; 6.2 pmol/ml in group B (p < 0.01), and the range was 6.0-6.2 and 6.2-6.4 pmol/ml in groups C and D, respectively (p < 0.05 for D). Histopathological assessment (vascular and inflammation damages) showed toxicity in group B (p < 0.05) and mild toxicity in group C. Damage was significantly lesser in group D than group B (p < 0.05). Spleen only showed toxicity after coadministration. These results suggest vascular and inflammation protective effects of sunitinib, not shown after biomarker analysis.
  9. Fulltext An effective ostrich oil bleaching technique using peroxide value as an indicator
    Palanisamy UD, Sivanathan M, Radhakrishnan AK, Haleagrahara N, Subramaniam T, Chiew GS
    Molecules, 2011 Jul 05;16(7):5709-19.
    PMID: 21730920 DOI: 10.3390/molecules16075709
    Ostrich oil has been used extensively in the cosmetic and pharmaceutical industries. However, rancidity causes undesirable chemical changes in flavour, colour, odour and nutritional value. Bleaching is an important process in refining ostrich oil. Bleaching refers to the removal of certain minor constituents (colour pigments, free fatty acid, peroxides, odour and non-fatty materials) from crude fats and oils to yield purified glycerides. There is a need to optimize the bleaching process of crude ostrich oil prior to its use for therapeutic purposes. The objective of our study was to establish an effective method to bleach ostrich oil using peroxide value as an indicator of refinement. In our study, we showed that natural earth clay was better than bentonite and acid-activated clay to bleach ostrich oil. It was also found that 1 hour incubation at a 150 °C was suitable to lower peroxide value by 90%. In addition, the nitrogen trap technique in the bleaching process was as effective as the continuous nitrogen flow technique and as such would be the recommended technique due to its cost effectiveness.
  10. Influence of serum concentration in retinoic acid and phorbol ester induced differentiation of SH-SY5Y human neuroblastoma cell line
    Magalingam KB, Radhakrishnan AK, Somanath SD, Md S, Haleagrahara N
    Mol Biol Rep, 2020 Nov;47(11):8775-8788.
    PMID: 33098048 DOI: 10.1007/s11033-020-05925-2
    Numerous protocols to establish dopaminergic phenotype in SH-SY5Y cells have been reported. In most of these protocols there are variations in concentration of serum used. In this paper, we compared the effects of high (10%), low (3%) and descending (2.5%/1%) serum concentration in differentiation medium containing different proportion of retinoic acid (RA) and 12-O-Tetradecanoylphorbol-13-acetate (TPA) or RA-only on the undifferentiated SH-SY5Y cells with regards to cell morphology, biochemical and gene expression alterations. Cells differentiated in culture medium containing low and descending serum concentrations showed increased number of neurite projections and reduced proliferation rates when compared to undifferentiated cells. The SH-SY5Y cells differentiated in culture medium containing 3% RA and low serum or descending (2.5%/1% RA/TPA) were found to be more susceptible to 6-hydroxydopamine (6-OHDA) induced cytotoxicity. Cells differentiated with RA/TPA or RA differentiated showed increased production of the α-synuclein (SNCA) neuroprotein and dopamine neurotransmitter compared to undifferentiated cells, regardless serum concentrations used. There was no significant difference in the expression of tyrosine hydroxylase (TH) gene between undifferentiated and differentiated SH-SY5Y cells. However, the expression of dopamine receptor D2 (DRD2) gene was markedly increased (p<0.05) in differentiated cells with 3% serum and RA only when compared to undifferentiated cells. In conclusion, to terminally differentiate SH-SY5Y cells to be used as a cell-based model to study Parkinson's disease (PD) to investigate molecular mechanisms and drug discovery, the optimal differentiation medium should contain 3% serum in RA-only.
  11. Quercetin glycosides induced neuroprotection by changes in the gene expression in a cellular model of Parkinson's disease
    Magalingam KB, Radhakrishnan A, Ramdas P, Haleagrahara N
    J Mol Neurosci, 2015 Mar;55(3):609-17.
    PMID: 25129099 DOI: 10.1007/s12031-014-0400-x
    Quercetin glycosides, rutin and isoquercitrin, are potent antioxidants that have been found to possess neuroprotective effect in diseases like Parkinson's and Alzheimer's disease. In the present study, we have examined the gene expression changes with rutin and isoquercitrin pretreatment on 6-hydroxydopamine (6-OHDA)-treated toxicity in rat pheochromocytoma (PC12) cells. PC12 cells were pretreated with rutin or isoquercitrin and subsequently exposed to 6-OHDA. Rutin-pretreated PC12 attenuated the Park2, Park5, Park7, Casp3, and Casp7 genes which were expressed significantly in the 6-OHDA-treated PC12 cells. Rutin upregulated the TH gene which is important in dopamine biosynthesis, but isoquercitrin pretreatment did not affect the expression of this gene. Both rutin and isoquercitrin pretreatments upregulated the ion transport and antiapoptotic genes (NSF and Opa1). The qPCR array data were further validated by qRT-PCR using four primers, Park5, Park7, Casp3, and TH. This finding suggests that changes in the expression levels of transcripts encoded by genes that participate in ubiquitin pathway and dopamine biosynthesis may be involved in Parkinson's disease.
  12. Fulltext Cardioprotective effects of glycyrrhizic acid against isoproterenol-induced myocardial ischemia in rats
    Haleagrahara N, Varkkey J, Chakravarthi S
    Int J Mol Sci, 2011;12(10):7100-13.
    PMID: 22072938 DOI: 10.3390/ijms12107100
    The aim of the present study was to look into the possible protective effects of glycyrrhizic acid (GA) against isoproterenol-induced acute myocardial infarction in Sprague-Dawley rats. The effect of three doses of glycyrrhizic acid in response to isoproterenol (ISO)-induced changes in 8-isoprostane, lipid hydroperoxides, super oxide dismutase and total glutathione were evaluated. Male Sprague-Dawley rats were divided into control, ISO-control, glycyrrhizic acid alone (in three doses-5, 10 and 20 mg/kg BW) and ISO with glycyrrhizic acid (in three doses) groups. ISO was administered at 85 mg/kg BW at two consecutive days and glycyrrhizic acid was administered intraperitoneally for 14 days. There was a significant increase in 8-isoprostane (IP) and lipid hydroperoxide (LPO) level in ISO-control group. A significant decrease in total superoxide dismutase (SOD) and total glutathione (GSH) was seen with ISO-induced acute myocardial infarction. Treatment with GA significantly increased SOD and GSH levels and decreased myocardial LPO and IP levels. Histopathologically, severe myocardial necrosis and nuclear pyknosis and hypertrophy were seen in ISO-control group, which was significantly reduced with GA treatment. Gycyrrhizic acid treatment proved to be effective against isoproterenol-induced acute myocardial infarction in rats and GA acts as a powerful antioxidant and reduces the myocardial lipid hydroperoxide and 8-isoprostane level.
  13. Rutin, a bioflavonoid antioxidant protects rat pheochromocytoma (PC-12) cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity
    Magalingam KB, Radhakrishnan A, Haleagrahara N
    Int J Mol Med, 2013 Jul;32(1):235-40.
    PMID: 23670213 DOI: 10.3892/ijmm.2013.1375
    Free radicals are widely known to be the major cause of human diseases such as neurodegenerative diseases, cancer, allergy and autoimmune diseases. Human cells are equipped with a powerful natural antioxidant enzyme network. However, antioxidants, particularly those originating from natural sources such as fruits and vegetables, are still considered essential. Rutin, a quercetin glycoside, has been proven to possess antioxidant potential. However, the neuroprotective effect of rutin in pheochromocytoma (PC-12) cells has not been studied extensively. Therefore, the present study was designed to establish the neuroprotective role of rutin as well as to elucidate the antioxidant mechanism of rutin in 6-hydroxydopamine (6-OHDA)-induced toxicity in PC-12 neuronal cells. PC-12 cells were pretreated with different concentrations of rutin for 4, 8 and 12 h and subsequently incubated with 6-OHDA for 24 h to induce oxidative stress. A significant cytoprotective activity was observed in rutin pretreated cells in a dose-dependent manner. Furthermore, there was marked activation of antioxidant enzymes including superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and total glutathione (GSH) in rutin pretreated cells compared to cells incubated with 6-OHDA alone. Rutin significantly reduced lipid peroxidation in 6-OHDA-induced PC-12 cells. On the basis of these observations, it was concluded that the bioflavonoid rutin inhibited 6-OHDA-induced neurotoxicity in PC-12 cells by improving antioxidant enzyme levels and inhibiting lipid peroxidation.
  14. Fulltext Protective effects of quercetin glycosides, rutin, and isoquercetrin against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rat pheochromocytoma (PC-12) cells
    Magalingam KB, Radhakrishnan A, Haleagrahara N
    Int J Immunopathol Pharmacol, 2016 Mar;29(1):30-9.
    PMID: 26542606 DOI: 10.1177/0394632015613039
    There is increasing evidence that free radicals induced oxidative stress is a major causative agent in the pathogenesis of neurodegenerative diseases, particularly Parkinson's disease. Quercetin glycosides, namely rutin and isoquercitrin, are flavonoid polyphenol compounds found ubiquitously in fruits and vegetables and have been known to possess antioxidant effects. This study was designed to compare the neuroprotective effects of quercetin glycosides rutin and isoquercitrin in 6-OHDA-induced rat pheochromocytoma (PC-12) cells. The results showed that both rutin and isoquercitrin significantly increased antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, and glutathione level that were attenuated by 6-OHDA in PC-12 cells. There was no significant difference in the activation of glutathione and glutathione peroxidase enzymes between rutin and isoquercitrin. These two glycosides were equally effective in suppressing lipid peroxidation in 6-OHDA-induced PC-12 cells as both compounds suppressed the malondialdehyde generation and prevented cell damage. In conclusion, quercetin glycosides rutin and isoquercetrin are having a significant neuroprotective effect against 6-OHDA toxicity in PC-12 cells.
  15. Modulation of C-reactive protein and tumour necrosis factor-α in collagen-induced arthritis in Dark Agouti rats: impact of collagen concentration on severity of arthritis
    Tudave D, Radhakrishnan A, Chakravarthi S, Haleagrahara N
    Inflamm Res, 2011 Oct;60(10):897-907.
    PMID: 21633874 DOI: 10.1007/s00011-011-0349-y
    OBJECTIVES: The study investigated the effect of collagen-induced arthritis in Dark Agouti (DA) rats on the level of C-reactive protein and inflammatory cytokine tumour necrosis factor-alpha (TNF-α).

    SUBJECTS: Female Dark Agouti (DA) rats.

    METHODS: Three different dosages of (2 mg/kg of body weight, 3 mg/kg of body weight and 4 mg/kg of body weight) collagen and complete Freund's adjuvant suspension were tested. After 45 days, serum C-reactive protein, TNF-α, superoxide dismutase and total glutathione assays were done. Radiographic and histopathological changes in the joints were compared.

    RESULTS: All three groups showed signs of arthritic changes, confirmed by histopathological and radiographic changes. Severe arthritic changes were seen in the rats injected with 4 mg/kg of body weight of collagen. There was a significant increase in C-reactive protein, TNF-α, super oxide dismutase and total glutathione levels in the plasma in arthritis rats and the changes were more significant with 4 mg/kg of collagen.

    CONCLUSION: These results demonstrated that the optimal dose to inject to experimental animals in order to get server arthritic changes was 4 mg/kg of collagen with complete Freund's adjuvant suspension. Severe arthritis changes induced significant elevation in plasma C-reactive protein and TNF-α levels.

  16. Protective effects of Etlingera elatior extract on lead acetate-induced changes in oxidative biomarkers in bone marrow of rats
    Haleagrahara N, Jackie T, Chakravarthi S, Rao M, Pasupathi T
    Food Chem Toxicol, 2010 Oct;48(10):2688-94.
    PMID: 20600524 DOI: 10.1016/j.fct.2010.06.041
    Several environmental toxins with toxic effects to the bone marrow have been identified. Pathology associated with lead intoxication is due to the cellular damage mediated by free radicals. In the current study, we examined the effect of Etlingera elatior extract on lead-induced changes in the oxidative biomarkers and histology of bone marrow of rats. Sprague-Dawley rats were exposed to 500 ppm lead acetate in their drinking water for 14 days. E. elatior extract was treated orally (100mg/kg body weight) in combination with, or after lead acetate treatment. The results showed that there was a significant increase in lipid hydroperoxide, protein carbonyl content and a significant decrease in total antioxidants, super oxide dismutase, glutathione peroxidase and glutathione--S-transferase in bone marrow after lead acetate exposure. Treatment with E. elatior decreased lipid hydroperoxides and protein carbonyl contents and significantly increased total antioxidants and antioxidant enzymes. Treatments with E. elatior extract also reduced, lead-induced histopathological damage in bone marrow. In conclusion, these data suggest that E. elatior has a powerful antioxidant effect, and it protects the lead acetate-induced bone marrow oxidative damage in rats.
  17. Effect of γ-tocotrienol in counteracting oxidative stress and joint damage in collagen-induced arthritis in rats
    Radhakrishnan A, Tudawe D, Chakravarthi S, Chiew GS, Haleagrahara N
    Exp Ther Med, 2014 May;7(5):1408-1414.
    PMID: 24940448
    Tocotrienols exhibit a significant anti-inflammatory and antioxidant effect in numerous human diseases. However, the anti-inflammatory and antioxidant effects of tocotrienols in arthritic conditions are not well documented. Therefore, the effect of γ-tocotrienol supplementation against oxidative stress and joint pathology in collagen-induced arthritis in rats was investigated in the present study. Adult female Dark Agouti rats were randomly divided into groups: Control, γ-tocotrienol alone, arthritis alone and arthritis with γ-tocotrienol. Arthritis was induced using 4 mg/kg body weight collagen in complete Freund's adjuvant. The rats were treated orally with 5 mg/kg body weight of γ-tocotrienol between day 21 and day 45. After 45 days, serum C-reactive protein (CRP), tumor necrosis factor (TNF)-α, superoxide dismutase (SOD) and total glutathione (GSH) assays were conducted. γ-tocotrienol significantly reduced the arthritis-induced changes in body weight, CRP, TNF-α, SOD and the total GSH levels. There was a significant reduction in the arthritis-induced histopathological changes in the γ-tocotrienol treatment group. The data indicated that administration of γ-tocotrienol resulted in a significant antioxidant and anti-inflammatory effect on collagen-induced arthritis; therefore, γ-tocotrienol may have therapeutic potential as a long-term anti-arthritic agent in rheumatoid arthritis therapy.
  18. Flavonoid quercetin protects against swimming stress-induced changes in oxidative biomarkers in the hypothalamus of rats
    Haleagrahara N, Radhakrishnan A, Lee N, Kumar P
    Eur J Pharmacol, 2009 Oct 25;621(1-3):46-52.
    PMID: 19744476 DOI: 10.1016/j.ejphar.2009.08.030
    Quercetin is a bioflavonoid abundant in onions, apples, tea and red wine and one of the most studied flavonoids. Dietary quercetin intake is suggested to be health promoting, but this assumption is mainly based on mechanistic studies performed in vitro. The objective of this study was to investigate the effect of quercetin on stress-induced changes in oxidative biomarkers in the hypothalamus of rats. Adult male Sprague Dawley rats were subjected to forced swimming stress for 45 min daily for 14 days. Effect of quercetin at three different doses (10, 20 and 30 mg/kg body weight) on serum corticosterone and oxidative biomarkers (lipid hydroperoxides, antioxidant enzymes and total antioxidants) was estimated. Swimming stress significantly increased the serum corticosterone and lipid hydroperoxide levels. A significant decrease in total antioxidant levels and super oxide dismutase, glutathione peroxidase and catalase levels was seen in the hypothalamus after stress and treatment with quercetin significantly increased these oxidative parameters and there was a significant decrease in lipid hydroperoxide levels. These data demonstrate that forced swimming stress produced a severe oxidative damage in the hypothalamus and treatment with quercetin markedly attenuated these stress-induced changes. Antioxidant action of quercetin may be beneficial for the prevention and treatment of stress-induced oxidative damage in the brain.
  19. Fulltext Neuroprotective effects of alpha lipoic Acid on haloperidol-induced oxidative stress in the rat brain
    Perera J, Tan JH, Jeevathayaparan S, Chakravarthi S, Haleagrahara N
    Cell Biosci, 2011;1(1):12.
    PMID: 21711768 DOI: 10.1186/2045-3701-1-12
    Haloperidol is an antipsychotic drug that exerts its' antipsychotic effects by inhibiting dopaminergic neurons. Although the exact pathophysiology of haloperidol extrapyramidal symptoms are not known, the role of reactive oxygen species in inducing oxidative stress has been proposed as one of the mechanisms of prolonged haloperidol-induced neurotoxicity. In the present study, we evaluate the protective effect of alpha lipoic acid against haloperidol-induced oxidative stress in the rat brain. Sprague Dawley rats were divided into control, alpha lipoic acid alone (100 mg/kg p.o for 21 days), haloperidol alone (2 mg/kg i.p for 21 days), and haloperidol with alpha lipoic acid groups (for 21 days). Haloperidol treatment significantly decreased levels of the brain antioxidant enzymes super oxide dismutase and glutathione peroxidase and concurrent treatment with alpha lipoic acid significantly reversed the oxidative effects of haloperidol. Histopathological changes revealed significant haloperidol-induced damage in the cerebral cortex, internal capsule, and substantia nigra. Alpha lipoic acid significantly reduced this damage and there were very little neuronal atrophy. Areas of angiogenesis were also seen in the alpha lipoic acid-treated group. In conclusion, the study proves that alpha lipoic acid treatment significantly reduces haloperidol-induced neuronal damage.
  20. N-acetylcysteine offers cardioprotection by decreasing cardiac lipid hydroperoxides and 8-isoprostane level in isoproterenol-induced cardiotoxicity in rats
    Haleagrahara N, Julian V, Chakravarthi S
    Cardiovasc Toxicol, 2011 Dec;11(4):373-81.
    PMID: 21796404 DOI: 10.1007/s12012-011-9132-0
    This study investigated the cardioprotective effect of N-acetylcysteine (NAC) on isoproterenol (ISO)-induced cardiotoxicity in rats. Male Sprague-Dawley rats were divided into control, NAC alone (100 mg/kg BW orally for 14 days), ISO-control (85 mg/kg BW), and ISO with NAC (for 14 days). Serum creatine kinase-MB and Lactate dehydrogenase were measured. From the heart homogenate lipid hydroperoxides (LPO), superoxide dismutase (SOD), total glutathione (GSH), and 8-isoprostane (IP) were measured. Histopathological examination of the heart was also carried out. There was a significant increase (P 
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links