Displaying publications 1 - 20 of 41 in total

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  1. Ambu, Stephen, Yin, Evelyn Synn Yeoh, Joon, Wah Mak, Chakravarthi, Srikumar
    MyJurnal
    The aim of the study was to assess the prevalence of Sarcocystis infection in wild and peri-urban rodents in some states in Peninsular Malaysia. The thigh muscle from these rodents were formalin preserved, sectioned and stained with hematoxylin and eosin and examined under light microscopy. Of the 146 muscle tissue examined only 73 were positive for Sarcocystis infection.
    Morphological identification showed the presence of some new morphological types to be present. Different species of Sarcocystis were seen in the sections but more extensive studies are needed to identify them to species level.
  2. 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.
  3. Haleagrahara N, Swaminathan M, Chakravarthi S, Radhakrishnan A
    Biomed Res Int, 2014;2014:539540.
    PMID: 25114906 DOI: 10.1155/2014/539540
    Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease primarily involving inflammation of the joints. Although the management of the disease has advanced significantly in the past three decades, there is still no cure for RA. The aim of this study was to determine the therapeutic efficacy of δ-tocotrienol, in the rat model of collagen-induced arthritis (CIA). Arthritis was induced by intradermal injection of collagen type II emulsified in complete Freund's adjuvant. CIA rats were orally treated with δ-tocotrienol (10 mg/kg) or glucosamine hydrochloride (300 mg/kg) from day 25 to 50. Efficacy was assessed based on the ability to reduce paw edema, histopathological changes, suppression of collagen-specific T-cells, and a reduction in C-reactive protein (CRP) levels. It was established that δ-tocotrienol had the most significant impact in lowering paw edema when compared to glucosamine treatment. Paw edema changes correlated well with histopathological analysis where there was a significant reversal of changes in groups treated with δ-tocotrienol. The results suggest that δ-tocotrienol is efficient in amelioration of collagen-induced arthritis. Vitamin E delta-tocotrienol may be of therapeutic value against rheumatoid arthritis.
  4. 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.
  5. 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.

  6. 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 
  7. Jackie T, Haleagrahara N, Chakravarthi S
    BMC Res Notes, 2011;4:67.
    PMID: 21414212 DOI: 10.1186/1756-0500-4-67
    Etlingera elatior or 'pink torch ginger' (Zingiberaceae) are widely cultivated in tropical countries and used as spices and food flavoring. The purpose of this study was to evaluate the antioxidant effects of Etlingera elatior against lead - induced changes in serum free radical scavenging enzymes and lipid hydroperoxides in rats.
  8. Manaharan T, Chakravarthi S, Radhakrishnan AK, Palanisamy UD
    Toxicol Rep, 2014;1:718-725.
    PMID: 28962285 DOI: 10.1016/j.toxrep.2014.09.006
    In this study, the acute and subchronic toxicity effect of the Syzygium aqueum leaf extract (SA) was evaluated. For the acute toxicity study, a single dose of 2000 mg/kg of the SA was given by oral-gavage to male Sprague-Dawley (SD) rats. The rats were observed for mortality and toxicity signs for 14 days. In the subchronic toxicity study the SA was administered orally at doses of 50, 100, and 200 mg/kg per day for 28 days to male SD rats. The animals were sacrificed at the end of the experiment. The parameters measured including food and water intake, body weight, absolute and relative organ weight, blood biochemical tests and histopathology observation. In both the acute and subchronic toxicity studies, SA did not show any visible signs of toxicity. There were also no significant differences between the control and SA treated rats in terms of their food and water intake, body weight, absolute and relative organ weight, biochemical parameters or gross and microscopic appearance of the organs. There were no acute or subchronic toxicity observed and our results indicate that this extract could be devoid of any toxic risk. This is the first in vivo study reported the safety and toxicity of SA.
  9. David SR, Malek N, Mahadi AH, Chakravarthi S, Rajabalaya R
    Drug Des Devel Ther, 2018;12:481-494.
    PMID: 29563773 DOI: 10.2147/DDDT.S146549
    Background: Peritonitis is the most serious complication of peritoneal dialysis. Staphylococcus aureus infections could lead to peritonitis which causes reversal of peritoneal dialysis treatment back to hemodialysis. The aim of this study was to develop a controlled release silicone adhesive-based mupirocin patch for prophylactic effect and analyze its antibacterial effectiveness against S. aureus.

    Methods: The matrix patches were prepared by using different polymers, with and without silicone adhesive, dibutyl sebacate and mupirocin. The patches were characterized for mechanical properties, drug content, moisture content, water absorption capacity and Fourier transform infrared spectrum. In vitro release studies were performed by using Franz diffusion cell. In vitro disk diffusion assay was performed on the Mueller-Hinton Agar plate to measure the zone of inhibition of the patches. The in vivo study was performed on four groups of rats with bacterial counts at three different time intervals, along with skin irritancy and histopathologic studies.

    Results: The patches showed appropriate average thickness (0.63-1.12 mm), tensile strength (5.08-10.08 MPa) and modulus of elasticity (21.53-42.19 MPa). The drug content ranged from 94.5% to 97.4%, while the moisture content and water absorption capacities at two relative humidities (75% and 93%) were in the range of 1.082-3.139 and 1.287-4.148 wt%, respectively. Fourier transform infrared spectra showed that there were no significant interactions between the polymer and the drug. The highest percentage of drug release at 8 hours was 47.94%. The highest zone of inhibition obtained was 28.3 mm against S. aureus. The in vivo studies showed that the bacterial colonies were fewer at 1 cm (7×101 CFU/mL) than at 2 cm (1.3×102 CFU/mL) over a 24-hour period. The patches were nonirritant to the skin, and histopathologic results also showed no toxic or damaging effects to the skin.

    Conclusion: The in vitro and in vivo studies indicated that controlled release patches reduced the migration of S. aureus on the live rat skin effectively, however, a longer duration of study is required to determine the effectiveness of the patch on a suitable peritonitis-induced animal model.

  10. Sundralingam U, Chakravarthi S, Radhakrishnan AK, Muniyandy S, Palanisamy UD
    Pharmaceutics, 2020 Aug 25;12(9).
    PMID: 32854385 DOI: 10.3390/pharmaceutics12090807
    Oral tamoxifen used in the prevention and treatment of ductal carcinoma in situ (DCIS) (estrogen-positive) patients has limited acceptance, due to its adverse side effects. The efficacy of tamoxifen is related to its major metabolite, 4-hydroxytamoxifen. Local transdermal therapy of 4-hydroxytamoxifen to the breast might avert the toxicity of oral tamoxifen, while maintaining efficacy. We aim to study the skin irritancy, as well as to evaluate the efficacy of the developed transfersome formulations, with/without emu oil, using a syngeneic mouse model of breast cancer. We also quantified tamoxifen/4-hydroxytamoxifen concentrations in blood plasma and performed histopathology. The skin irritancy test showed that the pure emu oil and transfersome formulations with or without the emu oil did not cause skin irritancy in the animals studied. A sensitive and specific LC-MS/MS method for the quantification of tamoxifen and 4-hydroxytamoxifen was developed and validated. Studies on tumor volume and necrosis (histopathology) using the breast cancer mouse model showed that the 4-OHT transfersomal formulations, with and without emu oil, showed comparable efficacy with that of orally administered tamoxifen. However, the transfersomal formulations, with and without emu oil, resulted in significantly lower (10.24 ± 0.07 and 32.45 ± 0.48 ng/mL, respectively) plasma concentrations of 4-hydroxytamoxifen, compared to the oral tamoxifen (TAMX) group (634.42 ± 7.54 ng/mL). This study demonstrated the potential use of emu oil in a local transdermal formulation for the treatment of breast cancer and its reduced adverse effects.
  11. Rajabalaya R, Leen G, Chellian J, Chakravarthi S, David SR
    Pharmaceutics, 2016;8(3).
    PMID: 27589789 DOI: 10.3390/pharmaceutics8030027
    The goal of this study was to formulate and evaluate side effects of transdermal delivery of proniosomal gel compared to oral tolterodine tartrate (TT) for the treatment of overactive bladder (OAB). Proniosomal gels are surfactants, lipids and soy lecithin, prepared by coacervation phase separation. Formulations were analyzed for drug entrapment efficiency (EE), vesicle size, surface morphology, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, in vitro skin permeation, and in vivo effects. The EE was 44.87%-91.68% and vesicle size was 253-845 nm for Span formulations and morphology showed a loose structure. The stability and skin irritancy test were also carried out for the optimized formulations. Span formulations with cholesterol-containing formulation S1 and glyceryl distearate as well as lecithin containing S3 formulation showed higher cumulative percent of permeation such as 42% and 35%, respectively. In the in vivo salivary secretion model, S1 proniosomal gel had faster recovery, less cholinergic side effect on the salivary gland compared with that of oral TT. Histologically, bladder of rats treated with the proniosomal gel formulation S1 showed morphological improvements greater than those treated with S3. This study demonstrates the potential of proniosomal vesicles for transdermal delivery of TT to treat OAB.
  12. Verma RK, Wong S, Chakravarthi S, Barua A
    J Clin Diagn Res, 2014 Apr;8(4):HC10-3.
    PMID: 24959464 DOI: 10.7860/JCDR/2014/7829.4286
    INTRODUCTION:Human Immunodeficiency virus infection (HIV) and Acquired Immunodeficiency Syndrome (AIDS) has become one of the most serious health problems in the world. Medical students awareness, attitudes and opinions must be assessed as they are leading health care professionals who provide treatment and care to the HIV and AIDS individuals. This survey was conducted to assess the level of awareness, attitudes and opinions of third year till fifth year medical students concerning HIV and AIDS from universities around Klang Valley area, Malaysia.
    MATERIALS AND METHODS:A total of 327 medical students of third to fifth been took part in the survey. Self prepared and self validated questionnaire was used to assess the study outcomes. Students were asked to fill the consent forms before filling the questionnaires. The results were analyzed by using SPSS version 17. A cross-sectional study among medical students was performed. Data was analyzed with non-parametric spearman's correlation test to find the difference at p-value < 0.05.
    RESULTS: A great majority knew that HIV can be spread via tattoo or body piercing (89.3%), from mother to child (97.9%), being a homosexual (93.3%) and even having circumcision for protection (71.9%). Also, they were aware that HIV cannot be transferred via sneezing and cough (95.1%), swimming pools (89.0%), and toilet seats (89.6%). However, only a few were aware of other modes of transmission, such as visiting the barbers (41.3%) , and having blood splashed on outer body surface including mouth and eyes (49.2%). Only a few negative attitudes were shown such as being unsure about keeping close vicinity to HIV patients and being unsure of whether HIV negative people should be allowed to marry HIV positive patients (median=3).
    CONCLUSION: An optimal plan of education with awareness campaign and preclinical experiences should be made in the future curriculum to increase the knowledge, confidence and minimize phobia among students.
    KEYWORDS: Cross-sectional study; Prevention; Transmission
    Study site: Two universities in Klang Valley, Malaysia
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. Ambikabothy J, Ibrahim H, Ambu S, Chakravarthi S, Awang K, Vejayan J
    J Ethnopharmacol, 2011 Sep 1;137(1):257-62.
    PMID: 21640180 DOI: 10.1016/j.jep.2011.05.013
    Evaluations of the anti-snake venom efficacy of Mimosa pudica tannin isolate (MPT) obtained from root of the plant.
  18. Ali A, Vasudevan R, Ismail P, Thiam Seong CL, Chakravarthi S
    J Renin Angiotensin Aldosterone Syst, 2015 Dec;16(4):1337-43.
    PMID: 21421653 DOI: 10.1177/1470320310392096
    Insertion/deletion (I/D) polymorphisms found in the angiotensin converting enzyme (ACE) gene have been associated with hypertension, diabetes and renal disease. The present study sought to determine the association of I/D polymorphisms of the ACE gene with end-stage renal disease (ESRD) patients in Malaysia.
  19. 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.
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