Browsing by Author "Raj K. Koiri"

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Acute and chronic hyperammonemia modulate antioxidant enzymes differently in cerebral cortex and cerebellum
(2008) Santosh Singh; Raj K. Koiri; Surendra Kumar Trigun
Studies on acute hyperammonemic models suggest a role of oxidative stress in neuropathology of ammonia toxicity. Mostly, a low grade chronic type hyperammonemia (HA) prevails in patients with liver diseases and causes derangements mainly in cerebellum associated functions. To understand whether cerebellum responds differently than other brain regions to chronic type HA with respect to oxidative stress, this article compares active levels of all the antioxidant enzymes vis a vis extent of oxidative damage in cerebral cortex and cerebellum of rats with acute and chronic HA induced by intra-peritoneal injection of ammonium acetate (successive doses of 10 × 103 & 8 × 103 μmol/kg b.w. at 30 min interval for acute and 8 × 103 μmol/kg b.w. daily up to 3 days for chronic HA). As compared to the respective control sets, cerebral cortex of acute HA rats showed significant decline (P < 0.01-0.001) in the levels of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) but with no change in glutathione reductase (GR). In cerebellum of acute HA rats, SOD, catalase and GR though declined significantly, GPx level was found to be stable. Contrary to this, during chronic HA, levels of SOD, catalase and GPx increased significantly in cerebral cortex, however, with a significant decline in the levels of SOD and GPx in cerebellum. The results suggest that most of the antioxidant enzymes decline during acute HA in both the brain regions. However, chronic HA induces adaptive changes, with respect to the critical antioxidant enzymes, in cerebral cortex and renders cerebellum susceptible to the oxidative stress. This is supported by ∼ 2- and 3-times increases in the level of lipid peroxidation in cerebellum during chronic and acute HA respectively, however, with no change in the cortex due to chronic HA. © 2007 Springer Science+Business Media, LLC.
An overview of natural plant products in the treatment of hepatocellular carcinoma
(Bentham Science Publishers B.V., 2018) Divya Rawat; Somi Shrivastava; Rayees A. Naik; Saurabh K. Chhonker; Aditi Mehrotra; Raj K. Koiri
Background: Liver cancer is the fifth most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Among the liver cancers, hepatocellular carcinoma has been reported to be responsible for 85-90% of primary liver cancer and it is the second most common cause of cancer mortality with 700,000 deaths documented annually. The major risk factors of HCC include chronic infections with the hepatitis B (HBV) or hepatitis C (HCV) virus, chronic liver diseases, alcoholism as well as dietary carcinogens, such as aflatoxins. Highest incidence rates are estimated to occur in Asia and Africa. Objective: The effectiveness of current man-made agents in treating chronic liver disease is not satisfactory and they have uninvited side effects. Herbal medicines are extensively used all over the world; however, there is still a vast gap in their acceptance by the scientific community. Plants are rich in secondary metabolites and phytochemicals obtained from both, dietary and non-dietary sources. Natural plant products are potent therapeutic as well as chemopreventive agents for numerous chronic diseases like cardiovascular, metabolic, neurodegenerative and neoplastic diseases. Results: Dietary phytochemicals such as curcumin, resveratrol, quercetin, silibinin, N-trans-feruloyl octopamine, lycopene, emodin, caffeine, urolithin A and Phloretin have been found to be useful for the treatment of HCC and other diseases. According to recent reports 60% of the anticancer medication in current use has been obtained from natural sources. Conclusion: Thus, derivatives from plants have played an essential role in cancer prevention due to their pleiotropic abilities to scavenge free radicals, inhibit cell growth and induce apoptosis. © 2018 Bentham Science Publishers.
Dimethyl sulfoxide activates tumor necrosis factorα-p53 mediated apoptosis and down regulates d-fructose-6-phosphate-2-kinase and lactate dehydrogenase-5 in Dalton's lymphoma in vivo
(2011) Raj K. Koiri; Surendra K. Trigun
Dimethyl sulfoxide (DMSO) is evident to induce apoptosis in certain tumor cells in vitro. However, its apoptotic mechanism remains unexplored in in vivo tumors. This article describes that DMSO, being non-toxic to the normal lymphocytes, up regulated TNFα and p53, declined Bcl-2/Bax ratio, activated caspase 9 and PARP-1 cleavage and produced apoptotic pattern of DNA ladder in Dalton's lymphoma (DL) in vivo. This was consistent with the declined expressions of tumor growth supportive glycolytic enzymes; inducible d-fructose-6-phosphate-2-kinase and lactate dehydrogenase-5 in the DL cells. The findings suggest induction of TNFα-p53-mitochondrial pathway of apoptosis by DMSO in a non-Hodgkin's lymphoma and support evolving concept of glycolytic inhibition led apoptosis in a tumor cell in vivo. © 2011 Elsevier Ltd.
Regression of Dalton's lymphoma in vivo via decline in lactate dehydrogenase and induction of apoptosis by a ruthenium(II)-complex containing 4-carboxy N-ethylbenzamide as ligand
(2009) Raj K. Koiri; Surendra K. Trigun; Lallan Mishra; Kiran Pandey; Deobrat Dixit; Santosh K. Dubey
Summary: A novel ruthenium(II)-complex containing 4-carboxy N-ethylbenzamide (Ru(II)-CNEB) was found to interact with and inhibit M4-lactate dehydrogenase (M4-LDH), a tumor growth supportive enzyme, at the tissue level. The present article describes modulation of M4-LDH by this compound in a T-cell lymphoma (Dalton's Lymphoma: DL) vis a vis regression of the tumor in vivo. The compound showed a dose dependent cytotoxicity to DL cells in vitro. When a non toxic dose (10 mg/kg bw i.p.) of Ru(II)-CNEB was administered to DL bearing mice, it also produced a significant decline in DL cell viability in vivo. The DL cells from Ru(II)-CNEB treated DL mice showed a significant decline in the level of M4-LDH with a concomitant release of this protein in the cell free ascitic fluid. A significant increase of nuclear DNA fragmentation in DL cells from Ru(II)-CNEB treated DL mice also coincided with the release of mitochondrial cytochrome c in those DL cells. Importantly, neither blood based biochemical markers of liver damage nor the normal patterns of LDH isozymes in other tissues were affected due to the treatment of DL mice with the compound. These results were also comparable with the effects of cisplatin (an anticancer drug) observed simultaneously on DL mice. The findings suggest that Ru(II)-CNEB is able to regress Dalton's lymphoma in vivo via declining M4-LDH and inducing mitochondrial dysfunction-apoptosis pathway without producing any toxicity to the normal tissues. © 2008 Springer Science+Business Media, LLC.
Ruthenium complex as enzyme modulator: Modulation of lactate dehydrogenase by a novel ruthenium(II) complex containing 4-carboxy N-ethylbenzamide as a ligand
(2007) Surendra K. Trigun; Raj K. Koiri; Lallan Mishra; Santosh K. Dubey; Santosh Singh; Pankaj Pandey
Ruthenium complex-protein interaction, particularly with respect to modulation of the enzymes associated to tumor development, is an evolving concept in understanding the mechanism of action of these complexes as anticancer agent. Lactate dehydrogenase (LDH; EC: 1.1.1.27) is critically implicated in maintaining tumor growth via 'Warburg effect' in cancerous cells. This article presents current status of Rucomplexes as enzyme inhibitors in general and a state of art on a novel ruthenium(II) complex containing 4-Carboxy-N-ethylbenzamide as an inhibitor of LDH. The 4-carboxy-N-ethylbenzamide (CNEB) was synthesized and characterized by single crystal X-ray measurement and complexed with cis-Ru(bpy)2Cl2.2H2O (bpy=2,2′bipyridine) resulting into synthesis of a [Ru(CNEB)2(bpy)2] 2PF6.0.5 NH4PF6] complex, Ru(II)-CNEB. The complex showed appreciable cytotoxicity on Dalton's lymphoma cells and a significant Ru(II)-CNEB-LDH interaction (Kc = 1.525 × 105 M-1). The later was further confirmed from luminescence quenching and gel retardation assays. The complex also caused a significant decline in the activities of purified LDH and LDH from mice liver extract. The complex was further characterized as a non-competitive inhibitor of LDH(Ki = 0.032 mM). Ru(II)-CNEB complex perfused mice liver also showed a significant decline in LDH activity coinciding with similar changes in the intensity of LDH bands on polyacrylamide gel electrophoresis. Thus, Ru(II)-CNEB complex, as a non-competitive inhibitor of LDH, seems to be a candidate for potential therapeutic applications. © 2007 Bentham Science Publishers Ltd.