Publications by authors named "Madan Kumar Arumugam"

6 Publications

  • Page 1 of 1

Elevated S-adenosylhomocysteine induces adipocyte dysfunction to promote alcohol-associated liver steatosis.

Sci Rep 2021 Jul 19;11(1):14693. Epub 2021 Jul 19.

Research Service (151), Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Avenue, Omaha, NE, 68105, USA.

It has been previously shown that chronic ethanol administration-induced increase in adipose tissue lipolysis and reduction in the secretion of protective adipokines collectively contribute to alcohol-associated liver disease (ALD) pathogenesis. Further studies have revealed that increased adipose S-adenosylhomocysteine (SAH) levels generate methylation defects that promote lipolysis. Here, we hypothesized that increased intracellular SAH alone causes additional related pathological changes in adipose tissue as seen with alcohol administration. To test this, we used 3-deazaadenosine (DZA), which selectively elevates intracellular SAH levels by blocking its hydrolysis. Fully differentiated 3T3-L1 adipocytes were treated in vitro for 48 h with DZA and analysed for lipolysis, adipokine release and differentiation status. DZA treatment enhanced adipocyte lipolysis, as judged by lower levels of intracellular triglycerides, reduced lipid droplet sizes and higher levels of glycerol and free fatty acids released into the culture medium. These findings coincided with activation of both adipose triglyceride lipase and hormone sensitive lipase. DZA treatment also significantly reduced adipocyte differentiation factors, impaired adiponectin and leptin secretion but increased release of pro-inflammatory cytokines, IL-6, TNF and MCP-1. Together, our results demonstrate that elevation of intracellular SAH alone by DZA treatment of 3T3-L1 adipocytes induces lipolysis and dysregulates adipokine secretion. Selective elevation of intracellular SAH by DZA treatment mimics ethanol's effects and induces adipose dysfunction. We conclude that alcohol-induced elevations in adipose SAH levels contribute to the pathogenesis and progression of ALD.
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http://dx.doi.org/10.1038/s41598-021-94180-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289835PMC
July 2021

An efficient and magnetically recoverable g-CN/ZnS/CoFeO nanocomposite for sustainable photodegradation of organic dye under UV-visible light illumination.

Environ Res 2021 Jun 17;201:111429. Epub 2021 Jun 17.

Advanced Materials Research Chair, Chemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.

Effective improvement of an easily recoverable photocatalyst is equally vital to its photocatalytic performance from a practical application view. The magnetically recoverable process is one of the easiest ways, provided the photocatalyst is magnetically strong enough to respond to an external magnetic field. Herein, we prepared graphitic carbon nitride nanosheet (g-CN), and ZnS quantum dots (QDs) supported ferromagnetic CoFeO nanoparticles (NPs) as the gCN/ZnS/CoFeO nanohybrid photocatalyst by a wet-impregnation method. The loading of CoFeO NPs in the g-CN/ZnS nanohybrid resulted in extended visible light absorption. The ferromagnetic g-CN/ZnS/CoFeO nanohybrid exhibited better visible-light-active photocatalytic performance (97.11%) against methylene blue (MB) dye, and it was easily separable from the aqueous solution by an external bar magnet. The g-CN/ZnS/CoFeO nanohybrid displayed excellent photostability and reusability after five consecutive cycles. The favourable band alignment and availability of a large number of active sites affected the better charge separation and enhanced photocatalytic response. The role of active species involved in the degradation of MB dye during photocatalyst by g-CN/ZnS/CoFeO nanohybrid was also investigated. Overall, this study provides a facile method for design eco-friendly and promising g-CN/ZnS/CoFeO nanohybrid photocatalyst as applicable in the eco-friendly dye degradation process.
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http://dx.doi.org/10.1016/j.envres.2021.111429DOI Listing
June 2021

Beneficial Effects of Betaine: A Comprehensive Review.

Biology (Basel) 2021 May 22;10(6). Epub 2021 May 22.

Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.

Medicinal herbs and many food ingredients possess favorable biological properties that contribute to their therapeutic activities. One such natural product is betaine, a stable, nontoxic natural substance that is present in animals, plants, and microorganisms. Betaine is also endogenously synthesized through the metabolism of choline or exogenously consumed through dietary intake. Betaine mainly functions as (i) an osmolyte and (ii) a methyl-group donor. This review describes the major physiological effects of betaine in whole-body health and its ability to protect against both liver- as well as non-liver-related diseases and conditions. Betaine's role in preventing/attenuating both alcohol-induced and metabolic-associated liver diseases has been well studied and is extensively reviewed here. Several studies show that betaine protects against the development of alcohol-induced hepatic steatosis, apoptosis, and accumulation of damaged proteins. Additionally, it can significantly prevent/attenuate progressive liver injury by preserving gut integrity and adipose function. The protective effects are primarily associated with the regulation of methionine metabolism through removing homocysteine and maintaining cellular SAM:SAH ratios. Similarly, betaine prevents metabolic-associated fatty liver disease and its progression. In addition, betaine has a neuroprotective role, preserves myocardial function, and prevents pancreatic steatosis. Betaine also attenuates oxidant stress, endoplasmic reticulum stress, inflammation, and cancer development. To conclude, betaine exerts significant therapeutic and biological effects that are potentially beneficial for alleviating a diverse number of human diseases and conditions.
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http://dx.doi.org/10.3390/biology10060456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224793PMC
May 2021

,-Ru(II)--cymene-poly(-vinylpyrrolidone) surface functionalized gold nanoparticles: from organoruthenium complex to nanomaterial for antiproliferative activity.

Dalton Trans 2021 Jun;50(23):8232-8242

Department of Chemistry, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu, Chennai, TN, India.

Organometallic Ru-arene complexes are promising as anticancer agents, but the lack of tumor uptake and poor solubility in the physiological medium impede their development. In order to deal with these challenges, we developed gold nanoparticles coated with Ru(arene)-functionalized PNVP-Py, where PNVP-Py is pyridine end-functionalized poly(N-vinylpyrrolidone). It is demonstrated that these particles exhibit higher anti-proliferative activity than the individual organometallic ruthenium(ii) complex of the type [Ru(η6-p-cymene)(NN)Cl]PF6, where NN is bis(4-methoxyphenylimino)acenaphthene, against colorectal adenocarcinoma cell lines. More specifically, a RuII(η6-p-cymene) complex containing a NN bidentate ligand has been prepared and characterized by spectral studies and X-ray crystallography. To tether the isolated complex onto the surface of the AuNPs, PNVP-Py, which contains a pyridine group at one end to coordinate to the Ru-complex and a suitable functional group at the other end to bind on the surface of the AuNPs, has been prepared and utilized to obtain the macromolecular complex [Ru(η6-p-cymene)(NN)(PNVP-Py)]Cl2. Next, stable Ru(p-cym)(NN)(PNVP-Py)@AuNPs were obtained via a ligand exchange reaction of citrate-stabilized AuNPs with a macromolecular complex by a direct 'grafting to' approach and characterized well. Despite the lower DNA cleavage activity, the nanoconjugate exhibits better cytotoxicity than the individual complex against HT-29 colorectal adenocarcinoma cells on account of its enhanced permeability across the cell membrane. The AO/EB staining assay revealed that the nanoconjugate is able to induce an apoptotic mode of cell death, which was further quantitatively evaluated by Annexin V-FITC/PI double assay. An immunofluorescence assay indicated the higher potency of the nanoconjugate to inhibit cyclin D1 gene expression that is required for cancer cell growth. To the best of our knowledge, this is the first report of the modification of an organometallic Ru(arene) complex into a Ru(arene)metallopolymer-gold nanoconjugate for the development of ruthenium-based nanomedicine for cancer treatment.
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http://dx.doi.org/10.1039/d1dt00694kDOI Listing
June 2021

Role of Elevated Intracellular S-Adenosylhomocysteine in the Pathogenesis of Alcohol-Related Liver Disease.

Cells 2020 06 23;9(6). Epub 2020 Jun 23.

Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.

Background: The earliest manifestation of alcohol-related liver disease (ALD) is steatosis, characterized by the accumulation of lipid droplets (LDs) in hepatocytes. Findings from our laboratory have indicated that many pathological changes, including steatosis, correlate with the alcohol-induced hepatocellular increases in S-adenosylhomocysteine (SAH). Based on these considerations, we hypothesized that an experimental increase in intracellular SAH alone will result in similar steatotic changes to those seen after alcohol exposure.

Methods: Freshly isolated rat hepatocytes grown on collagen-coated plates were exposed to serum-free medium containing 50 µmol/L oleic acid and varying concentrations of 3-deazaadenosine (DZA) to experimentally elevate intracellular SAH levels.

Results: Overnight exposure to DZA treatment dose-dependently increased hepatocellular triglyceride accumulation, which was also evident by morphological visualization of larger-sized LDs. The rise in triglycerides and LDs accompanied increases in mRNA and protein levels of several LD-associated proteins known to regulate LD number and size. Furthermore, DZA treatment caused a decline in the levels of lipases that prevent fat accumulation as well as increased the expression of factors involved in lipogenesis and fatty acid mobilization. Collectively, our results indicate that the elevation of intracellular SAH is sufficient to promote fat accumulation in hepatocytes, which is similar to that seen after alcohol exposure.
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http://dx.doi.org/10.3390/cells9061526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349643PMC
June 2020

Reactive oxygen species generation and mitochondrial dysfunction for the initiation of apoptotic cell death in human hepatocellular carcinoma HepG2 cells by a cyclic dipeptide Cyclo(-Pro-Tyr).

Mol Biol Rep 2020 May 4;47(5):3347-3359. Epub 2020 Apr 4.

Cancer Biology Lab, Centre for Molecular and Nanomedical Sciences, Sathyabama Institute of Science and Technology, Chennai, 600119, India.

Cyclic dipeptides are increasingly gaining importance as considering its significant biological and pharmacological activities. This study was aimed to investigate the anticancer activity of a dipeptide Cyclo(-Pro-Tyr) (DP) identified from marine sponge Callyspongia fistularis symbiont Bacillus pumilus AMK1 and the underlying apoptotic mechanisms in the liver cancer HepG2 cell lines. MTT assay was done to demonstrate the cytotoxic effect of DP in HepG2 cells and mouse Fibroblast McCoy cells. Initially, apoptosis inducing activity of DP was identified using propidium iodide (PI) and acridine orange/ethidium bromide (AO/EB) dual staining, then it was confirmed by DNA fragmentation assay and western blotting analysis of apoptosis related markers Bax, Bcl-2, cytochrome c, caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP). Rhodamine 123 staining was performed to observe DP effects on the mitochondrial membrane potential (MMP) and DCFH-DA (Dichloro-dihydro-fluorescein diacetate) staining was done to measure the intracellular reactive oxygen species (ROS) levels. The MTT results revealed that DP initiated dose-dependent cytotoxicity in HepG2 cells, but no significant toxicity in mouse Fibroblast McCoy cells treated with DP at the specified concentrations. DP induced apoptosis, which is confirmed by the appearance of apoptotic bodies with PI and AO/EB dual staining, and DNA fragmentation. DP significantly elevated the Bax/Bcl-2 ratio, disrupted the mitochondrial membrane potential (MMP), enhanced cytochrome c release from mitochondria, increased caspase-3 activation, the cleavage of PARP and increased intracellular reactive oxygen species (ROS) levels. Besides this, DP successfully inhibited the phosphorylation of PI3K, AKT and increased PTEN expression. These results suggested DP might have anti-cancer effect by initiating apoptosis through mitochondrial dysfunction and downregulating PI3K/Akt signaling pathway in HepG2 cells with no toxicity effect on normal fibroblast cells. Therefore, DP may be developed as a potential alternative therapeutic agent for treating hepatocellular carcinoma.
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http://dx.doi.org/10.1007/s11033-020-05407-5DOI Listing
May 2020
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