Publications by authors named "Arumugam Suyavaran"

12 Publications

  • Page 1 of 1

Fermented Soy Beverage Q-CAN Plus Consumption Improves Serum Cholesterol and Cytokines.

J Med Food 2020 May 22;23(5):560-563. Epub 2019 Nov 22.

Department of Pediatrics (General Pediatrics), Yale University School of Medicine, New Haven, Connecticut, USA.

Soy-based beverages are well recognized for their rich nutritional contents and positive health benefits. However, there is little information regarding the composition of various commercially available soy-based beverages and uncertainty among patients regarding the utility of fermented soy products. Current study evaluates the health benefits of QCAN Plus-an easily available fermented soy drink. This study was performed in lean ( = 10) and obese ( = 10) subjects. The subjects were observed during pre-soy (weeks -2, -1, and 0), on-soy (weeks 1, 2, 3, and 4), and post-soy (weeks 6, 8, 10, and 12) periods. The serum samples during these visits were subjected to lipid profile analysis and multiplex assay for cytokines. The results revealed that total cholesterol and low-density lipoprotein (LDL) cholesterol levels were significantly reduced in both lean and obese individuals during on-soy ( ≤ .05). Furthermore, cytokines such as platelet-derived growth factor (PDGF) AA and AB/BB were significantly lowered on-soy compared with pre-soy ( ≤ .05) in lean subjects and PDGF AA, IL-1RA, and GMCSF were significantly reduced on-soy ( ≤ .05) in obese subjects. In addition, a qualitative and quantitative analysis of the Q-CAN Plus by a third-party laboratory confirmed its chemical and microbial safety. Our preliminary study on Q-CAN Plus ensures its safety for consumption and highlights its hypolipidemic and suppressive effect on certain cytokines. These observations and relevant studies in future might guide clinicians in future to consider Q-CAN Plus as a therapeutic nutritional supplement.
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http://dx.doi.org/10.1089/jmf.2019.0116DOI Listing
May 2020

Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation.

Am J Physiol Gastrointest Liver Physiol 2019 10 14;317(4):G387-G397. Epub 2019 Aug 14.

Section of Digestive Diseases, Yale University School of medicine, New Haven, Connecticut.

The cardiac glycoside digoxin was identified as a potent suppressor of pyruvate kinase isoform 2-hypoxia-inducible factor-α (PKM2-HIF-1α) pathway activation in liver injury mouse models via intraperitoneal injection. We have assessed the therapeutic effects of digoxin to reduce nonalcoholic steatohepatitis (NASH) by the clinically relevant oral route in mice and analyzed the cellular basis for this effect with differential involvement of liver cell subsets. C57BL/6J male mice were placed on a high-fat diet (HFD) for 10 wk and started concurrently with the gavage of digoxin (2.5, 0.5, 0.125 mg/kg twice a week) for 5 wk. Digoxin significantly reduced HFD-induced hepatic damage, steatosis, and liver inflammation across a wide dosage range. The lowest dose of digoxin (0.125 mg/kg) showed significant protective effects against liver injury and sterile inflammation. Consistently, digoxin attenuated HIF-1α sustained NLRP3 inflammasome activation in macrophages. We have reported for the first time that PKM2 is upregulated in hepatocytes with hepatic steatosis, and digoxin directly improved hepatocyte mitochondrial dysfunction and steatosis. Mechanistically, digoxin directly bound to PKM2 and inhibited PKM2 targeting HIF-1α transactivation without affecting PKM2 enzyme activation. Thus, oral digoxin showed potential to therapeutically inhibit liver injury in NASH through the regulation of PKM2-HIF-1α pathway activation with involvement of multiple cell types. Because of the large clinical experience with oral digoxin, this may have significant clinical applicability in human NASH. This study is the first to assess the therapeutic efficacy of oral digoxin on nonalcoholic steatohepatitis (NASH) in a high-fat diet (HFD) mouse model and to determine the divergent of cell type-specific effects. Oral digoxin reduced liver damage, steatosis, and inflammation in HFD mice. Digoxin attenuated hypoxia-inducible factor (HIF)-1α axis-sustained inflammasome activity in macrophages and hepatic oxidative stress response in hepatocytes via the regulation of PKM2-HIF-1α axis pathway activation. Oral digoxin may have significant clinical applicability in human NASH.
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http://dx.doi.org/10.1152/ajpgi.00054.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842989PMC
October 2019

Unveiling anticancer potential of glibenclamide: Its synergistic cytotoxicity with doxorubicin on cancer cells.

J Pharm Biomed Anal 2018 May 14;154:294-301. Epub 2018 Mar 14.

Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry 605 014, India. Electronic address:

Drug repurposing has been an emerging therapeutic strategy, which involves exploration of a new therapeutic approach for the use of an existing drug. Glibenclamide (Gli) is an anti-diabetic sulfonylurea drug extensively used for the treatment of type-2 diabetes, it has also been shown to possess anti-proliferative effect against several types of tumors. The present study was executed to understand the mechanisms underlying the interaction of Gli with DNA under physiological conditions. The binding mechanism of Gli with DNA was scrutinized by UV-vis absorption spectroscopy and fluorescence emission spectroscopy. The conformational changes and electrochemical properties were analyzed by circular dichroism spectroscopy and cyclic voltammetry. Isothermal titration calorimetry was employed to examine the thermodynamic changes and molecular docking technique used to analyze the interaction mode of Gli with DNA. The spectroscopic studies revealed that Gli interacts with DNA through groove binding mode. Further, isothermal titration calorimetry depicted a stronger mode of interaction favorably groove-binding. Recently, systemic combination therapy has shown significant promise in inhibiting multiple targets simultaneously yielding high therapeutic competence with lesser side effects. With this concern, we intended to study the combined cytotoxicity of Gli with doxorubicin (Dox). The results of MTT assay and acridine orange (AO)/ethidium bromide (EtBr) staining showed synergistic cytotoxicity of Gli + Dox combination on HepG2 & A549 cells. The present study documents the intricate mechanism of Gli-DNA interaction and delivers a multifaceted access for chemotherapy by Gli + Dox combination.
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http://dx.doi.org/10.1016/j.jpba.2018.03.025DOI Listing
May 2018

Synthesis and characterisation of arsenic nanoparticles and its interaction with DNA and cytotoxic potential on breast cancer cells.

Chem Biol Interact 2018 Nov 22;295:73-83. Epub 2017 Dec 22.

Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry 605 014, India. Electronic address:

Therapeutic applications of arsenic trioxide (ATO) are limited due to their severe adverse effects. However, nanoparticles of ATO might possess inimitable biologic effects based on their structure and size which differ from their parent molecules. Based on this conception, AsNPs were synthesized from ATO and comparatively analysed for their interaction mechanism with DNA using spectroscopic & electrochemical techniques. Finally, anti-proliferative activity was assessed against different breast cancer cells (MDA-MB-231 & MCF-7) and normal non-cancerous cells (HEK-293). The DNA interaction study revealed that AsNPs and ATO exhibit binding constant values in the order of 10 which indicates strong binding interaction. Binding of AsNPs did not disturb the structural integrity of DNA, on the other hand an opposing effect was observed with ATO through biophysical techniques. Further, in vitro study, confirms cytotoxicity of ATO and AsNPs against different cells, however at particular concentration ATO exhibits more cytotoxicity than that of AsNPs. Furthermore, cytotoxicity was confirmed through acridine orange and comet assay. In conclusion, AsNPs are safer than ATO with comparable efficacy and might be a suitable candidate for the development of novel therapeutic agent against breast cancer and other solid tumours.
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http://dx.doi.org/10.1016/j.cbi.2017.12.025DOI Listing
November 2018

Anticancer potential of ZnO nanoparticle-ferulic acid conjugate on Huh-7 and HepG2 cells and diethyl nitrosamine induced hepatocellular cancer on Wistar albino rat.

Nanomedicine 2018 02 21;14(2):415-428. Epub 2017 Nov 21.

Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, India. Electronic address:

Drawbacks and limitations of recently available therapies to hepatocellular cancer (HCC) devoted the scientist to focus on emerging new strategies. ZnO nanoparticles (ZnONPs) based chemotherapeutics has been emanating as a promising approach to maximize therapeutic synergy facilitating the discovery of novel multitargeted combinations. In the present study we conjugated ZnONPs with ferulic acid (ZnONPs-FAC) characterized by computational, spectroscopic and microscopic techniques. In vitro anticancer potential has been evaluated by assessing cell viability, morphology, ROS generation, mitochondrial membrane permeability, comet assay, immunofluorescent staining of 8-OHdG, Ki67 and γ-H2AX, cell cycle analysis and western blot analysis and in vivo anticancer potential against DEN induced HCC was analyzed by histopathological and immunohistochemical methods. The results revealed that ZnONPs-FAC induces cell death through apoptosis and can suppress the DEN-induced HCC. Our study documents therapeutic potential of nanoparticle conjugated with phytochemicals, suggesting a new platform for combinatorial chemotherapy.
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http://dx.doi.org/10.1016/j.nano.2017.11.003DOI Listing
February 2018

Neutrophil extracellular traps in acrolein promoted hepatic ischemia reperfusion injury: Therapeutic potential of NOX2 and p38MAPK inhibitors.

J Cell Physiol 2018 04 28;233(4):3244-3261. Epub 2017 Sep 28.

Department of Biochemistry and Molecular Biology, School of life sciences, Pondicherry University, Pondicherry, India.

Neutrophil is a significant contributor to ischemia reperfusion (IR) induced liver tissue damage. However, the exact role of neutrophils in IR induced innate immune activation and liver damage is not quite clear. Our study sheds light on the role of chronic oxidative stress end products in worsening the IR inflammatory process by neutrophil recruitment and activation following liver surgery. We employed specific inhibitors for molecular targets-NOX2 (NADPH oxidase 2) and P38 MAPK (Mitogen activated protein kinase) signal to counteract neutrophil activation and neutrophil extracellular trap (NET) release induced liver damage in IR injury. We found that acrolein initiated neutrophil chemotaxis and induced NET release both in vitro and in vivo. Acrolein exposure caused NET induced nuclear and mitochondrial damage in HepG2 cells as well as aggravated the IR injury in rat liver. Pretreatment with F-apocynin and naringin, efficiently suppressed acrolein induced NET release in vitro. Notably, it suppressed the expression of inflammatory cytokines, P38MAPK-ERK activation, and apoptotic signals in rat liver exposed to acrolein and subjected to IR. Moreover, this combination effectively attenuated acrolein induced NET release and hepatic IR injury. In the current study we have shown that the acrolein accumulation in liver due to chronic stress, is responsible for neutrophil recruitment and its activation leading to NET induced liver damage during surgery. Our study shows that therapeutic targeting of NOX2 and P38MAPK signaling in patients with chronic hepatic disorders would improve post operative hepatic function and survival.
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http://dx.doi.org/10.1002/jcp.26167DOI Listing
April 2018

Troxerutin with copper generates oxidative stress in cancer cells: Its possible chemotherapeutic mechanism against hepatocellular carcinoma.

J Cell Physiol 2018 Mar 3;233(3):1775-1790. Epub 2017 Aug 3.

Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, India.

Troxerutin (TXER) a rutin derivative is known for its anticancer effect against hepatocellular carcinoma (HCC). As part of large study, recently we have shown TXER interact with genetic material and its anti-mutagenic property. In the present study we have explored its possible mode of action in HCC. Since TXER alone did not show significant anticancer effect on Huh-7 cells, in vitro biochemical assays were performed for determining anticancer efficacy of TXER + metal complex using transition metals such as Cu, Zn, and Fe. The anticancer efficacy of TXER + Cu on Huh-7 cells were evaluated using MTT assay, DCFDA, JC-1 staining, comet assay, cell cycle analysis, immunocytochemistry, and Western blotting. Non-toxic nature of TXER was analyzed on primary rat hepatocytes. The in vivo efficacy of TXER was tested in N-nitrosodiethylamine initiated and γ-benzene hexachloride and partial hepatectomy promoted rat liver cancer. Liver markers, transition metal levels, histopathological examination, and expression levels of GST-P, 8-OHdG and Ki-67 were studied to assess the in vivo anticancer effect of TXER. We observed that TXER + Cu induced extensive cellular death on Huh-7 cells through generating free radicals and did not possess any toxic effect on normal hepatocytes. The in vivo studies revealed that TXER possess significant anti-cancer effect as assessed through improved liver markers and suppressed GST-P, 8-OHdG, and Ki-67 expression. TXER treatment reduced the hepatic Cu level in cancer bearing animals. Current study brings the putative mechanism involved in anti-cancer effect of TXER, further it will help to formulate phytoconstituents coupled anti-cancer drug for effective treatment of HCC.
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http://dx.doi.org/10.1002/jcp.26061DOI Listing
March 2018

Selenium nanoparticles synthesized in aqueous extract of Allium sativum perturbs the structural integrity of Calf thymus DNA through intercalation and groove binding.

Mater Sci Eng C Mater Biol Appl 2017 May 7;74:597-608. Epub 2017 Feb 7.

Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry 605 014, India. Electronic address:

Biomedical application of selenium nanoparticles (SeNPs) demands the eco-friendly composite for synthesis of SeNPs. The present study reports an aqueous extract of Allium sativum (AqEAS) plug-up the current need. Modern spectroscopic, microscopic and gravimetric techniques were employed to characterize the synthesized nanoparticles. Characterization studies revealed the formation of crystalline spherical shaped SeNPs. FTIR spectrum brings out the presence of different functional groups in AqEAS, which influence the SeNPs formation and stabilization. Furthermore the different aspects of the interaction between SeNPs and CT-DNA were scrutinized by various spectroscopic and cyclic voltametric studies. The results reveals the intercalation and groove binding mode of interaction of SeNPs with stacked base pair of CT-DNA. The Stern-Volmer quenching constant (K) were found to be 7.02×10M- (ethidium bromide), 4.22×10 M- (acridine orange) and 7.6×10M- (Hoechst) indicating strong binding of SeNPs with CT-DNA. The SeNPs - CT-DNA interactions were directly visualized by atomic force microscopy. The present study unveils the cost effective, innocuous, highly stable SeNPs intricate mechanism of DNA interaction, which will be a milestone in DNA targeted chemotherapy.
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http://dx.doi.org/10.1016/j.msec.2017.02.003DOI Listing
May 2017

Preconditioning methods in the management of hepatic ischemia reperfusion- induced injury: Update on molecular and future perspectives.

Hepatol Res 2017 Jan 10;47(1):31-48. Epub 2016 May 10.

Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, India.

Hepatic IR (ischemia reperfusion) injury is a commonly encountered obstacle in the post-operative management of hepatic surgery. Hepatic IR occurs during 'Pringle maneuver' for reduction of blood loss or during a brief period of cold storage followed by reperfusion of liver grafts. The stress induced during hepatic IR, triggers a spectrum of cellular responses leading to the varying degrees of hepatic complications which in turn affect the post operative care. Different preconditioning methods either activate or subdue different sets of molecular signals, resulting in varied levels of protection against hepatic IR injury. Yet, there is a serious lacuna in the knowledge regarding the choice of preconditioning methods and the resulting molecular changes in order to assess the efficiency and choice of these methods correctly. This review provides an update on the various preconditioning approaches such as surgical/ischemic, antioxidant, pharmaceutical and genetic preconditioning strategies published during last six years (2009-2015). Further, we discuss the attenuation or inhibition of specific inflammatory, apoptotic and necrotic markers in the various experimental models of liver IR subjected to different preconditioning strategies. While enlisting the controversies in the ischemic preconditioning strategy, we bring out the uncertainties in the existing molecular targets and their reliability in the attenuation of hepatic IR injury. Future research studies would include the novel preconditioning strategies employ i) the targeted gene silencing of key molecular targets inducing IR, ii) hyper expression of beneficial molecular signals against IR via gene transfer techniques. The above studies would see the combination of these latest techniques with the established preconditioning strategies for better post-operative hepatic management.
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http://dx.doi.org/10.1111/hepr.12706DOI Listing
January 2017

Nutrient profile of porridge made from Eleusine coracana (L.) grains: effect of germination and fermentation.

J Food Sci Technol 2015 Sep 14;52(9):6024-30. Epub 2015 Jan 14.

Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, 605 014 India.

Porridge (koozh) is one of the traditional foods made from Eleusine coracana L. grains (Finger millet). It is a soft food prepared from processed (germinated & fermented) finger millet flour (FMF). However, in the modern world of fast food, koozh is usually prepared from non-processed (non-germinated & non-fermented) FMF. Hence, present study was undertaken to evaluate the macro and micro nutrient contents in koozh prepared from germinated (fermented & non-fermented) and non-germinated (fermented & non-fermented) FMF. Highest protein, carbohydrate and glycoprotein contents were found in koozh prepared from germinated & non-fermented FMF. The free amino acid contents are higher in germinated & fermented condition when compare to other preparations. No significant change was observed in the calorific value of all preparations. There is no statistical difference in macro-nutrients & micro-nutrients minerals such as calcium, iron, magnesium, manganese, phosphorous and zinc among all the preparations. However, copper content is higher in non-germinated condition, whereas selenium, silicon and sulphur are higher in germinated FMF when compared to others. Significant level of total phenol, total flavonoid and free radical scavenging activity was observed in all preparations, which increased further during fermentation. The present observations, lead us to conclude that koozh prepared from germinated & non-fermented FMF contains higher level of carbohydrate, protein and glycoprotein, however germinated & fermented koozh has increased aminoacids, phytochemicals and free radical scavenging activity. Hence it is suggested that the consumption of koozh made from germinated & fermented FMF may provide easily digestible and energetic nutrients for healthier life.
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http://dx.doi.org/10.1007/s13197-015-1713-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4554619PMC
September 2015

Synthesis and biological evaluation of isoindoloisoquinolinone, pyroloisoquinolinone and benzoquinazolinone derivatives as poly(ADP-ribose) polymerase-1 inhibitors.

Bioorg Med Chem 2015 Feb 19;23(3):488-98. Epub 2014 Dec 19.

Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry 605 014, India. Electronic address:

A series of novel fused isoquinolinones with isoindoloisoquinolinone, pyroloisoquinolinone, and benzoquinalizinone skeletons were synthesized from corresponding phenethylimides. The isoquinolinone derivatives were evaluated for their protective effect on chicken erythrocytes subjected to oxidative damage. The effect of isoquinolinone derivatives were analysed by estimation of cell viability, antioxidant enzyme activities, DNA damage (comet assay), PARP-1 inhibition assay and molecular docking of the compounds with PARP-1 active site. The compounds CRR-271, CRR-288 and CRR-224+225 showed significant protective effect at 100 μM concentration. The PARP-1 inhibition assay revealed the IC50 values of CRR-271, CRR-288 and CRR-224+225 as <200 nM, further molecular docking studies shows higher binding energies with PARP-1 active site. Interesting findings in this study suggest that the novel isoquinolinone derivatives inhibit PARP-1 activity and protect cells against oxidative DNA damage, which could be implemented in the treatment of inflammatory diseases.
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http://dx.doi.org/10.1016/j.bmc.2014.12.017DOI Listing
February 2015

TNF-α suppression by glutathione preconditioning attenuates hepatic ischemia reperfusion injury in young and aged rats.

Inflamm Res 2015 Jan 25;64(1):71-81. Epub 2014 Nov 25.

Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, 605014, India.

Background And Aim: Hepatic ischemia reperfusion (I/R) stimulates Kupffer cells and initiates injury through tumor necrosis factor-α (TNF-α) upregulation. Aim of this study was to compare the variable effects of reduced glutathione (GSH) pre-treatment on I/R liver injury in young and aged rats.

Methods: Wistar male rats were sorted into young (groups I-III) and aged (groups IV-VI). All groups except sham (groups I and IV) were subjected to 90-min ischemia and 2-h reperfusion. The treatment groups received 200 mg/kg bwt (groups III and VI) of GSH, 30 min prior to I/R. Variable effects of GSH were studied by transaminase activities, thiobarbituric acid-reactive substances (TBARS), GSH level, GSH/oxidized GSH (GSSG) ratio, TNF-α level, apoptotic markers and confirmed by histopathological observations.

Results: Our findings revealed that I/R inflicted more liver damage in aged rats than young rats. The GSH treatment prior to surgery significantly lowered the serum transaminase activities, hepatic TBARS level and effectively restored the GSH/GSSG ratio in both young and aged rats more remarkably in the mitochondria. Western analysis depicted that the GSH treatment effectively suppressed TNF-α expression and apoptotic markers in both young and aged rats. These findings were further confirmed by terminal deoxynucleotide transferase dUTP nick end labeling assay and histopathological observations of liver sections of young and aged rats.

Conclusion: Restoration of GSH/GSSG ratio through GSH pre-conditioning inhibits TNF-α and apoptosis in hepatic I/R injury. Hence, GSH pre-conditioning may be utilized in both young and aged individuals during liver transplantation/surgery for better post-operative outcomes.
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http://dx.doi.org/10.1007/s00011-014-0785-6DOI Listing
January 2015