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- 저자 : Mishra Siddhartha Kumar (검색결과 4 건)
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Siddhartha Kumar Mishra,김환묵,강주희,이창우,오승현,류준선,배윤수 한국분자세포생물학회 2013 Molecules and cells Vol.36 No.3
Midazolam is a widely used anesthetic of the benzodiazepine class that has shown cytotoxicity and apoptosis-inducing activity in neuronal cells and lymphocytes. This study aims to evaluate the effect of midazolam on growth of K562 human leukemia cells and HT29 colon cancer cells. The in vivo effect of midazolam was investigated in BALB/ c-nu mice bearing K562 and HT29 cells human tumor xenografts. The results show that midazolam decreased the viability of K562 and HT29 cells by inducing apoptosis and S phase cell-cycle arrest in a concentration-dependent manner. Midazolam activated caspase-9, capspase-3 and PARP indicating induction of the mitochondrial intrinsic pathway of apoptosis. Midazolam lowered mitochondrial membrane potential and increased apoptotic DNA fragmentation. Midazolam showed reactive oxygen species (ROS) scavenging activity through inhibition of NADPH oxidase 2 (Nox2) enzyme activity in K562 cells. Midazolam caused inhibition of pERK1/2 signaling which led to inhi-bition of the anti-apoptotic proteins Bcl-XL and XIAP and phosphorylation activation of the pro-apoptotic protein Bid. Midazolam inhibited growth of HT29 tumors in xeno-graft mice. Collectively our results demonstrate that midazolam caused growth inhibition of cancer cells via activation of the mitochondrial intrinsic pathway of apoptosis and inhibited HT29 tumor growth in xenograft mice. The mechanism underlying these effects of midazolam might be suppression of ROS production leading to modulation of apoptosis and growth regulatory proteins. These findings present possible clinical implications of midazolam as an anesthetic to relieve pain during in vivo anticancer drug delivery and to enhance anticancer efficacy through its ROS-scavenging and pro-apoptotic properties.
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Rai Ravina,Ahmad Zaved,Jain Subodh Kumar,Jat Deepali,Mishra Siddhartha Kumar 한국독성학회 2024 Toxicological Research Vol.40 No.1
Aluminum is a widely used metal substance in daily life activities that has been shown to cause severe hepato-nephrotoxicity with long-term exposure. Natural dietary flavonoids are being utilized as a newer pharmaceutical approach against various acute and chronic diseases. Naringenin (NAR) has shown efficient therapeutic properties, including effects against metal toxicities. However, the protective efficacy of NAR on aluminum chloride ( AlCl3)-induced hepato-renal toxicity needs investigation as aluminum has shown serious environmental toxicity and bioaccumulation behavior. In this study, mice were treated with AlCl3 (10 mg/kg b.w./day) to assess toxicities, and a group of mice were co-treated with NAR (10 mg/kg b.w./ day) to assess the protective effects of NAR against hepato-nephrotoxicity. The levels of blood serum enzymes, oxidative stress biomarkers, inflammatory cytokines, and the apoptosis marker caspase-3 were measured using histological examinations. NAR treatment in AlCl3- treated mice resulted in maintained levels of liver and kidney function enzymes and lipid profiles. NAR treatment attenuated oxidative stress by regulating the levels of nitric oxide, advance oxidation of protein products, protein carbonylation, and lipid peroxidation. NAR also replenished reduced antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and reduced the levels of glutathione and oxidized glutathione. NAR regulated the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and elevated the levels of anti-inflammatory cytokines (IL-4, IL-10, and IFN-γ). The histological study further confirmed the protective effects of NAR against AlCl3- induced hepato-renal alterations. NAR decreased the expression of caspase-3 as a mechanism of protective effects against apoptotic damage in the liver and kidney of AlCl3- treated mice. In summary, this study demonstrated the antioxidant and anti-inflammatory properties of NAR, leading to the suppression of AlCl3- triggered hepato-renal apoptosis and histological alterations. The results suggest that aluminum toxicity needs to be monitored in daily life usage, and supplementation of the natural dietary flavonoid naringenin may help maintain liver and kidney health.
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Muhammad Torequl Islam,Md. Roich Khan,Siddhartha Kumar Mishra 경희대학교 융합한의과학연구소 2019 Oriental Pharmacy and Experimental Medicine Vol.19 No.2
An in depth review on Nigella sativa and its derived constituents has been necessitated which has been sketched in this paper from the research reports obtained from PubMed and ScienceDirect databases. Findings of this meticulous review suggest that N. sativa possesses various important phytoconstituents and derived compounds with diverse biological effects including antioxidant, anti-inflammatory, anti-bacterial, anti-fungal, anti-parasitic, anti-protozoal, antiviral, cytotoxic, anticancer, and neuro-, gastro-, cardio-, hepato- and nephro-protective activities. In addition, N. sativa implies beneficiary effects on reproductive, pulmonary and immune systems along with diabetes mellitus (type 2 diabetes), fertility, breast cancer, dermatological complications, dehydration, dyspepsia, osmotic balance and others. Amongst several isolated chemical moieties of N. sativa, thymoquinone may be one of the best targets for treatment of microbial infections, inflammations, cancer, metabolic syndromes, and many other diseases. The N. sativa is evident to promote health in some non-clinical and clinical studies and it may serve to be one of the best sources for modern phyto medicine.
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