Arun Kumar

Sulforaphane mitigates genotoxicity induced by radiation and anticancer drugs in human lymphocytes

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2013

Sulforaphane, present in cruciferous vegetables such as broccoli, is a dietary anticancer agent. ... more Sulforaphane, present in cruciferous vegetables such as broccoli, is a dietary anticancer agent. Sulforaphane, added 2 or 20 h following phytohemaglutinin stimulation to cultured peripheral blood lymphocytes of individuals accidentally exposed to mixed and ␤-radiation, reduced the micronucleus frequency by up to 70%. Studies with whole blood cultures obtained from healthy volunteers confirmed the ability of sulforaphane to ameliorate -radiation-induced genotoxicity and to reduce micronucleus induction by other DNA-damaging anticancer agents, such as bleomycin and doxorubicin. This reduction in genotoxicity in lymphocytes treated at the G 0 or G 1 stage suggests a role for sulforaphane in modulating DNA repair. Sulforaphane also countered the radiation-induced increase in lymphocyte HDAC activity, to control levels, when cells were treated 2 h after exposure, and enhanced histone H4 acetylation status. Sulforaphane post-irradiation treatment enhanced the CD 34 + Lin -cell population in culture. Sulforaphane has therapeutic potential for management of the late effects of radiation.

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Sesamol ameliorates radiation induced DNA damage in hematopoietic system of whole body γ-irradiated mice

Environmental and molecular mutagenesis, Jan 2, 2017

Ionizing radiation exposure is harmful and at high doses can lead to acute hematopoietic radiatio... more Ionizing radiation exposure is harmful and at high doses can lead to acute hematopoietic radiation syndrome. Therefore, agents that can protect hematopoietic system are important for development of radioprotector. Sesamol is a potential molecule for development of radioprotector due to its strong free radical scavenging and antioxidant properties. In the present study, sesamol was evaluated for its role in DNA damage and repair in hematopoietic system of γ-irradiated CB57BL/6 mice and compared with amifostine. C57BL/6 male mice were administered with sesamol 20 mg/kg (i.p.) followed by 2 Gy whole body irradiation (WBI) at 30 min. Mice were sacrificed at 0.5, 3, 24 h postirradiation; bone marrow, splenocytes, and peripheral blood lymphocytes were isolated to measure DNA damages and repair using alkaline comet,γ-H2AXand micronucleus assays. An increase in % of tail DNA was observed in all organs of WBI mice. Whereas in pre-administered sesamol reduced %DNA in tail (P ≤ 0.05). Sesamol ...

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Protective effect of sesamol against (60)Co γ-ray-induced hematopoietic and gastrointestinal injury in C57BL/6 male mice

Free radical research, Jan 9, 2015

Protection of γ-ray-induced injury in hematopoietic and gastrointestinal systems is rational for ... more Protection of γ-ray-induced injury in hematopoietic and gastrointestinal systems is rational for developing radioprotector. The objective of this study, therefore, was to investigate the radioprotective efficacy and mechanisms underlying sesamol in amelioration of γ-ray-induced hematopoietic and gastrointestinal (GI) injury in mice. C57BL/6 male mice were pre-treated with a single dose (100 or 50 mg/kg, 30 min prior) of sesamol through intra-peritoneal route and exposed to LD50/30 (7.5 Gy) and sub-lethal (5 Gy) dose of γ-radiation. Thirty-day survival against 7.5 Gy was monitored. Sesamol (100 mg/kg) pre-treatment reduced radiation-induced mortality and resulted survival of about 100 % against 7.5 Gy of γ-irradiation. Whole-body irradiation drastically depleted hematopoietic progenitor stem cells in bone marrow, B cells and T cell sub-populations and splenocytes proliferation in spleen on day 4, which were significantly protected in sesamol pre-treated mice. This was associated with...

Sesamol attenuates genotoxicity in bone marrow cells of whole-body γ-irradiated mice

Mutagenesis, Jan 11, 2015

Ionising radiation causes free radical-mediated damage in cellular DNA. This damage is manifested... more Ionising radiation causes free radical-mediated damage in cellular DNA. This damage is manifested as chromosomal aberrations and micronuclei (MN) in proliferating cells. Sesamol, present in sesame seeds, has the potential to scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic damage in cells. The aim of this study was to investigate the radioprotective potential of sesamol in bone marrow cells of mice and related haematopoietic system against radiation-induced genotoxicity. A comparative study with melatonin was designed for assessing the radioprotective potential of sesamol. C57BL/6 mice were administered intraperitoneally with either sesamol or melatonin (10 and 20mg/kg body weight) 30min prior to 2-Gy whole-body irradiation (WBI) and sacrificed after 24h. Total chromosomal aberrations (TCA), MN and cell cycle analyses were performed using bone marrow cells. The comet assay was performed on bone marrow cells, splenocytes and lymphocytes. Blood was drawn ...

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Sesamol ameliorates radiation induced DNA damage in hematopoietic system of whole body γ-irradiated mice.

Ionizing radiation exposure is harmful and at high doses can lead to acute hematopoietic radiatio... more Ionizing radiation exposure is harmful and at high doses can lead to acute hematopoietic radiation syndrome. Therefore, agents that can protect hematopoietic system are important for development of radioprotector. Sesamol is a potential molecule for development of radioprotector due to its strong free radical scavenging and antioxidant properties. In the present study, sesamol was evaluated for its role in DNA damage and repair in hematopoietic system of γ-irradiated CB57BL/6 mice and compared with amifostine. C57BL/6 male mice were administered with sesamol 20 mg/kg (i.p.) followed by 2 Gy whole body irradiation (WBI) at 30 min. Mice were sacrificed at 0.5, 3, 24 h postirradiation; bone marrow, splenocytes, and peripheral blood lymphocytes were isolated to measure DNA damages and repair using alkaline comet,γ-H2AXand micronucleus assays. An increase in % of tail DNA was observed in all organs of WBI mice. Whereas in pre-administered sesamol reduced %DNA in tail (P ≤ 0.05). Sesamol has also reduced formation of radiation induced γ-H2AX foci after 0.5 h in these organs and further lowered to respective control values at 24 h of WBI. Similar reduction of % DNA in tail and γ-H2AX foci were observed with amifostine (P ≤ 0.05). Analysis of mnPCE frequency at 24 h has revealed similar extent of protection by sesamol and amifostine. Interestingly, both sesamol and amifostine, alone and with radiation, also increased the granulocytes count significantly compared to the control (P ≤ 0.05). These findings suggest that sesamol has strong potential to protect hematopoietic system by lowering radiation induced DNA damages and can prevent acute hematopoietic syndrome in mice.

Sesamol attenuates genotoxicity in bone marrow cells of whole-body γ-irradiated mice

by Arun Kumar, Jawahar Adhikari, and Sandeep Choudhary

Mutagenesis, Jan 11, 2015

Ionising radiation causes free radical-mediated damage in cellular DNA. This damage is manifested... more Ionising radiation causes free radical-mediated damage in cellular DNA. This damage is manifested as chromosomal aberrations and micronuclei (MN) in proliferating cells. Sesamol, present in sesame seeds, has the potential to scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic damage in cells. The aim of this study was to investigate the radioprotective potential of sesamol in bone marrow cells of mice and related haematopoietic system against radiation-induced genotoxicity. A comparative study with melatonin was designed for assessing the radioprotective potential of sesamol. C57BL/6 mice were administered intraperitoneally with either sesamol or melatonin (10 and 20mg/kg body weight) 30min prior to 2-Gy whole-body irradiation (WBI) and sacrificed after 24h. Total chromosomal aberrations (TCA), MN and cell cycle analyses were performed using bone marrow cells. The comet assay was performed on bone marrow cells, splenocytes and lymphocytes. Blood was drawn ...

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Protective effect of sesamol against (60)Co γ-ray-induced hematopoietic and gastrointestinal injury in C57BL/6 male mice

by Arun Kumar and Jawahar Adhikari

Free radical research, Jan 9, 2015

Protection of γ-ray-induced injury in hematopoietic and gastrointestinal systems is rational for ... more Protection of γ-ray-induced injury in hematopoietic and gastrointestinal systems is rational for developing radioprotector. The objective of this study, therefore, was to investigate the radioprotective efficacy and mechanisms underlying sesamol in amelioration of γ-ray-induced hematopoietic and gastrointestinal (GI) injury in mice. C57BL/6 male mice were pre-treated with a single dose (100 or 50 mg/kg, 30 min prior) of sesamol through intra-peritoneal route and exposed to LD50/30 (7.5 Gy) and sub-lethal (5 Gy) dose of γ-radiation. Thirty-day survival against 7.5 Gy was monitored. Sesamol (100 mg/kg) pre-treatment reduced radiation-induced mortality and resulted survival of about 100 % against 7.5 Gy of γ-irradiation. Whole-body irradiation drastically depleted hematopoietic progenitor stem cells in bone marrow, B cells and T cell sub-populations and splenocytes proliferation in spleen on day 4, which were significantly protected in sesamol pre-treated mice. This was associated with...

Sesamol attenuates genotoxicity in bone marrow cells of whole-body γ-irradiated mice

by Arun Kumar and Akanchha M Tripathi

Ionising radiation causes free radical–mediated damage in cellular DNA. This damage is manifested... more Ionising radiation causes free radical–mediated damage in cellular DNA. This damage is manifested as chromosomal aberrations and micronuclei (MN) in proliferating cells. Sesamol, present in sesame seeds, has the potential to scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic damage in cells. The aim of this study was to investigate the radioprotective potential of sesamol in bone marrow cells of mice and related haematopoietic system against radiation-induced genotoxicity. A comparative study with melatonin was designed for assessing the radioprotective potential of sesamol. C57BL/6 mice were administered intraperitoneally with either sesamol or melatonin (10 and 20mg/kg body weight) 30min prior to 2-Gy whole-body irradiation (WBI) and sacrificed after 24h. Total chromosomal aberrations (TCA), MN and cell cycle analyses were performed using bone marrow cells. The comet assay was performed on bone marrow cells, splenocytes and lymphocytes. Blood was drawn to study haematological parameters. Prophylactic doses of sesamol (10 and 20mg/kg) in irradiated mice reduced TCA and micronucleated polychromatic erythrocyte frequency in bone marrow cells by 57% and 50%, respectively, in comparison with radiation-only groups. Sesamol-reduced radiation-induced apoptosis and facilitated cell proliferation. In the comet assay, sesamol (20mg/kg) treatment reduced radiation-induced comets (% DNA in tail) compared with radiation only (P < 0.05). Sesamol also increased granulocyte populations in peripheral blood similar to melatonin. Overall, the radioprotective efficacy of sesamol was found to be similar to that of melatonin. Sesamol treatment also showed recovery of relative spleen weight at 24h of WBI. The results strongly suggest the radioprotective efficacy of sesamol in the haematopoietic system of mice.

© The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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Sulforaphane mitigates genotoxicity induced by radiation andanticancer drugs in human lymphocytes

by Arun Kumar and Paban Agraqala

tSulforaphane, present in cruciferous vegetables such as broccoli, is a dietary anticancer agent.... more tSulforaphane, present in cruciferous vegetables such as broccoli, is a dietary anticancer agent. Sul-foraphane, added 2 or 20 h following phytohemaglutinin stimulation to cultured peripheral bloodlymphocytes of individuals accidentally exposed to mixed and -radiation, reduced the micronucleusfrequency by up to 70%. Studies with whole blood cultures obtained from healthy volunteers confirmedthe ability of sulforaphane to ameliorate -radiation-induced genotoxicity and to reduce micronucleusinduction by other DNA-damaging anticancer agents, such as bleomycin and doxorubicin. This reductionin genotoxicity in lymphocytes treated at the G0or G1stage suggests a role for sulforaphane in mod-ulating DNA repair. Sulforaphane also countered the radiation-induced increase in lymphocyte HDACactivity, to control levels, when cells were treated 2 h after exposure, and enhanced histone H4 acety-lation status. Sulforaphane post-irradiation treatment enhanced the CD 34+Lin−cell population in culture.Sulforaphane has therapeutic potential for management of the late effects of radiation

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