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Podophyllum hexandrum-Mediated Survival Protection and Restoration of Other Cellular Injuries in Lethally Irradiated Mice.

Sankhwar S, Gupta ML, Gupta V, Verma S, Suri KA, Devi M, Sharma P, Khan EA, Alam MS - Evid Based Complement Alternat Med (2011)

Bottom Line: In the treated irradiated groups, there was a steep reduction in the counts initially, but this phase did not prolong.At later intervals, thymus was found fully regressed.In G-001M pre-treated irradiated groups also, thymocytes decreased till the 5th day but thereafter rejuvenated and within 30 days of treatment the values were close to normal.

View Article: PubMed Central - PubMed

Affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Majumdar Marg, Timarpur, New Delhi 110054, India.

ABSTRACT
This study aims at the development of a safe and effective formulation to counter the effects of lethal irradiation. The sub-fraction (G-001M), prepared from Podophyllum hexandrum has rendered high degree of survival (>90%) at a dose of 6 mg kg(-1) body weight (intramuscular) in lethally irradiated mice. Therapeutic dose of G-001M, at about 20 times lower concentration than its LD(100), has revealed a DRF of 1.62. Comet assay studies in peripheral blood leukocytes have reflected that, treatment of G-001M before irradiation has significantly reduced DNA tail length (P < .001) and DNA damage score (P < .001), as compared to radiation-only group. Spleen cell counts in irradiated animals had declined drastically at the very first day of exposure, and the fall continued till the 5th day (P < .001). In the treated irradiated groups, there was a steep reduction in the counts initially, but this phase did not prolong. More than 60% decline in thymocytes of irradiated group animals was registered at 5 h of irradiation when compared with controls, and the fall progressed further downwards with the similar pace till 5th day of exposure (P < .001). At later intervals, thymus was found fully regressed. In G-001M pre-treated irradiated groups also, thymocytes decreased till the 5th day but thereafter rejuvenated and within 30 days of treatment the values were close to normal. Current studies have explicitly indicated that, G-001M in very small doses has not only rendered high survivability in lethally irradiated mice, but also protected their cellular DNA, besides supporting fast replenishment of the immune system.

No MeSH data available.


Related in: MedlinePlus

Effect of P. hexandrum sub-fraction (G-001M) on DNA damage in peripheral blood leucocytes of whole body irradiated (10 Gy) mice. Measurement of DNA damage was done at different time intervals using comet assay in terms of tail length (mean ± SD). Experiments were done in triplicate with three animals in each group. Data points are mean values of 100 cells from each groups. j: Normal versus 15 min 10 Gy; k: l5 min l0 Gy versus 15 min (G-001M + 10 Gy); l: 120 min 10 Gy versus l20 min (G-001M + 10 Gy); m: 24 h 10 Gy versus 24 h (G-001M + 10 Gy) (**P < .001, ns, non significant).
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fig8: Effect of P. hexandrum sub-fraction (G-001M) on DNA damage in peripheral blood leucocytes of whole body irradiated (10 Gy) mice. Measurement of DNA damage was done at different time intervals using comet assay in terms of tail length (mean ± SD). Experiments were done in triplicate with three animals in each group. Data points are mean values of 100 cells from each groups. j: Normal versus 15 min 10 Gy; k: l5 min l0 Gy versus 15 min (G-001M + 10 Gy); l: 120 min 10 Gy versus l20 min (G-001M + 10 Gy); m: 24 h 10 Gy versus 24 h (G-001M + 10 Gy) (**P < .001, ns, non significant).

Mentions: Whole body lethal irradiation (10 Gy) in mice infuses apparent damage to cellular DNA. The measurement of DNA damage in terms of tail length, depending on various doses of G-001M and at different time intervals, is expressed in Figures 7 and 8, respectively. The DNA damage score data has not been shown in tabular or figure form. Exposure to lethal doses of gamma radiation increased DNA tail length to 29.9 ± 1.67 μm (P = .000, control versus 10 Gy) and DNA damage score to 97.3 (15 min post irradiation), against control values of 4.86 ± 0.79 μm and 18, respectively, in peripheral blood leukocytes of irradiated mice. However, both DNA tail length and DNA damage score receded with respect to increase in sampling time. At 120 min post irradiation the tail length and DNA damage score decreased to 20.87 ± 1.64 μm and 68.1, respectively. Within 24 h of study, DNA tail length (8.1 ± 0.95 μm) and DNA damage score (31.5) in radiation exposed group were found close to control group (P = .117, ns). Pretreatment of single dose of G-001M (6 mg kg−1 body weight) in lethally irradiated mice extended nearly 60% protection to peripheral blood leukocytes as DNA tail length reduced to 12.2 ± 1.28 μm (P = .000), and DNA damage score to 48.6 (15 min post irradiation). Sampling at 120 min post irradiation in pre-treated irradiated group revealed further shortening of tail length to 8.3 ± 1.04 μm, and reduction in DNA damage score to 29. The similar trend continued at 24 h also, where DNA tail length shortened to 6 ± 0.78 μm and DNA damage score to 23.3 (Figure 8). Concentrations of G-001M below 5 mg and more than 7 mg kg−1 body weight were found less efficient in exhibiting protection to leukocytic DNA, as depicted in Figure 7. Pre-administration of 10 mg kg−1 body weight of G-001M could decrease the DNA tail length (15 min sampling time) up to 18.8 ± 0.81 μm only, as against 7.28 ± 0.52 μm in 6 mg kg−1 body weight treated group.


Podophyllum hexandrum-Mediated Survival Protection and Restoration of Other Cellular Injuries in Lethally Irradiated Mice.

Sankhwar S, Gupta ML, Gupta V, Verma S, Suri KA, Devi M, Sharma P, Khan EA, Alam MS - Evid Based Complement Alternat Med (2011)

Effect of P. hexandrum sub-fraction (G-001M) on DNA damage in peripheral blood leucocytes of whole body irradiated (10 Gy) mice. Measurement of DNA damage was done at different time intervals using comet assay in terms of tail length (mean ± SD). Experiments were done in triplicate with three animals in each group. Data points are mean values of 100 cells from each groups. j: Normal versus 15 min 10 Gy; k: l5 min l0 Gy versus 15 min (G-001M + 10 Gy); l: 120 min 10 Gy versus l20 min (G-001M + 10 Gy); m: 24 h 10 Gy versus 24 h (G-001M + 10 Gy) (**P < .001, ns, non significant).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig8: Effect of P. hexandrum sub-fraction (G-001M) on DNA damage in peripheral blood leucocytes of whole body irradiated (10 Gy) mice. Measurement of DNA damage was done at different time intervals using comet assay in terms of tail length (mean ± SD). Experiments were done in triplicate with three animals in each group. Data points are mean values of 100 cells from each groups. j: Normal versus 15 min 10 Gy; k: l5 min l0 Gy versus 15 min (G-001M + 10 Gy); l: 120 min 10 Gy versus l20 min (G-001M + 10 Gy); m: 24 h 10 Gy versus 24 h (G-001M + 10 Gy) (**P < .001, ns, non significant).
Mentions: Whole body lethal irradiation (10 Gy) in mice infuses apparent damage to cellular DNA. The measurement of DNA damage in terms of tail length, depending on various doses of G-001M and at different time intervals, is expressed in Figures 7 and 8, respectively. The DNA damage score data has not been shown in tabular or figure form. Exposure to lethal doses of gamma radiation increased DNA tail length to 29.9 ± 1.67 μm (P = .000, control versus 10 Gy) and DNA damage score to 97.3 (15 min post irradiation), against control values of 4.86 ± 0.79 μm and 18, respectively, in peripheral blood leukocytes of irradiated mice. However, both DNA tail length and DNA damage score receded with respect to increase in sampling time. At 120 min post irradiation the tail length and DNA damage score decreased to 20.87 ± 1.64 μm and 68.1, respectively. Within 24 h of study, DNA tail length (8.1 ± 0.95 μm) and DNA damage score (31.5) in radiation exposed group were found close to control group (P = .117, ns). Pretreatment of single dose of G-001M (6 mg kg−1 body weight) in lethally irradiated mice extended nearly 60% protection to peripheral blood leukocytes as DNA tail length reduced to 12.2 ± 1.28 μm (P = .000), and DNA damage score to 48.6 (15 min post irradiation). Sampling at 120 min post irradiation in pre-treated irradiated group revealed further shortening of tail length to 8.3 ± 1.04 μm, and reduction in DNA damage score to 29. The similar trend continued at 24 h also, where DNA tail length shortened to 6 ± 0.78 μm and DNA damage score to 23.3 (Figure 8). Concentrations of G-001M below 5 mg and more than 7 mg kg−1 body weight were found less efficient in exhibiting protection to leukocytic DNA, as depicted in Figure 7. Pre-administration of 10 mg kg−1 body weight of G-001M could decrease the DNA tail length (15 min sampling time) up to 18.8 ± 0.81 μm only, as against 7.28 ± 0.52 μm in 6 mg kg−1 body weight treated group.

Bottom Line: In the treated irradiated groups, there was a steep reduction in the counts initially, but this phase did not prolong.At later intervals, thymus was found fully regressed.In G-001M pre-treated irradiated groups also, thymocytes decreased till the 5th day but thereafter rejuvenated and within 30 days of treatment the values were close to normal.

View Article: PubMed Central - PubMed

Affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Majumdar Marg, Timarpur, New Delhi 110054, India.

ABSTRACT
This study aims at the development of a safe and effective formulation to counter the effects of lethal irradiation. The sub-fraction (G-001M), prepared from Podophyllum hexandrum has rendered high degree of survival (>90%) at a dose of 6 mg kg(-1) body weight (intramuscular) in lethally irradiated mice. Therapeutic dose of G-001M, at about 20 times lower concentration than its LD(100), has revealed a DRF of 1.62. Comet assay studies in peripheral blood leukocytes have reflected that, treatment of G-001M before irradiation has significantly reduced DNA tail length (P < .001) and DNA damage score (P < .001), as compared to radiation-only group. Spleen cell counts in irradiated animals had declined drastically at the very first day of exposure, and the fall continued till the 5th day (P < .001). In the treated irradiated groups, there was a steep reduction in the counts initially, but this phase did not prolong. More than 60% decline in thymocytes of irradiated group animals was registered at 5 h of irradiation when compared with controls, and the fall progressed further downwards with the similar pace till 5th day of exposure (P < .001). At later intervals, thymus was found fully regressed. In G-001M pre-treated irradiated groups also, thymocytes decreased till the 5th day but thereafter rejuvenated and within 30 days of treatment the values were close to normal. Current studies have explicitly indicated that, G-001M in very small doses has not only rendered high survivability in lethally irradiated mice, but also protected their cellular DNA, besides supporting fast replenishment of the immune system.

No MeSH data available.


Related in: MedlinePlus