Countering effects of a combination of podophyllotoxin, podophyllotoxin β-D-glucoside and rutin hydrate in minimizing radiation induced chromosomal damage, ROS and apoptosis in human blood lymphocytes

Dutta, Saurav K.; Yashavarddhan, M.H.; Srivastava, Nitya N.; Ranjan, Rajiv; Bajaj, Sania; Kalita, Bhargab; Singh, Abhinav; Flora, S.J.S.; Gupta, Manju Lata

doi:10.1016/j.fct.2016.03.007

Cited by 10 publications

(3 citation statements)

References 40 publications

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“…During this study, p53 level was obtained to be similar in G-003M and amifostine pretreated mice. Antiapoptotic attribute of the formulation is due to reversible cell cycle arrest property (G2/M) of podophyllotoxin present in G-003M ( 25 ). DNA damage and faulty repair, the prerequisite of radiation-induced apoptosis and necrosis, was found amended by G-003M pretreatment.…”

Section: Discussionmentioning

confidence: 99%

“…However, the current study is designed to investigate the protective efficacy of G-003M (combination of podophyllotoxin and rutin) against lethal radiation-induced damage to mice bone marrow and spleen. Podophyllotoxin has been demonstrated for its DNA-protecting ability by reversible cell cycle arrest (G2/M) via inhibition of tubulin polymerization ( 25 , 26 ). During this stage, cells remain in quiescent stage and therefore are more radioresistant.…”

Section: Introductionmentioning

confidence: 99%

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Podophyllotoxin and Rutin Modulates Ionizing Radiation-Induced Oxidative Stress and Apoptotic Cell Death in Mice Bone Marrow and Spleen

et al. 2017

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The present study is aimed to investigate the radioprotective efficacy of G-003M (combination of podophyllotoxin and rutin) against gamma radiation-induced oxidative stress and subsequent cell death in mice bone marrow and spleen. Prophylactic administration of G-003M (−1 h) rendered more than 85% survival in mice exposed to 9 Gy (lethal dose) with dose reduction factor of 1.26. G-003M pretreated mice demonstrated significantly reduced level of reactive oxygen species, membrane lipid peroxidation, and retained glutathione level. In the same group, we obtained increased expression of master redox regulator, nuclear factor erythroid-derived like-2 factor (Nrf-2), and its downstream targets (heme oxygenase-1, Nqo-1, glutathione S-transferase, and thioredoxin reductase-1). In addition, G-003M preadministration has also shown a significant reduction in Keap-1 level (Nrf-2 inhibitor). Radiation-induced lethality was significantly amended in combination-treated (G-003M) mice as demonstrated by reduced 8-OHdG, annexin V FITC+ cells, and restored mitochondrial membrane potential. Expression of antiapoptotic protein Bcl-2 and Bcl-xL was restored in G-003M pretreated group. However, proapoptotic proteins (Puma, Bax, Bak, Caspase-3, and Caspase-7) were significantly declined in this group. Further analysis of immune cells revealed G-003M-mediated restoration of CD3 and CD19 receptor, which was found decreased to significant level following irradiation. Similarly, Gr-1, a marker of granulocytes, was also retained by G-003M administration prior to radiation. Modulatory potential of this formulation (G-003M) can be exploited as a safe and effective countermeasure against radiation-induced lymphohemopoietic injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Podophyllotoxin and Rutin Modulates Ionizing Radiation-Induced Oxidative Stress and Apoptotic Cell Death in Mice Bone Marrow and Spleen

et al. 2017

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“…Rutin has been reported to decrease oxidative stress by regulating oxidative stress related genes and proteins [33,34,35]. Quercetin, also identified as a component of RE-CE, together with rutin have antioxidant and radioprotective potential in mice exposed to γ-radiation [36,37,38].…”

Section: Discussionmentioning

confidence: 99%

Rutin-Enriched Extract from Coriandrum sativum L. Ameliorates Ionizing Radiation-Induced Hematopoietic Injury

Han

Xue

Zhao

et al. 2017

IJMS

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Hematopoietic injury is a major cause of mortality in radiation accidents and a primary side effect in patients undergoing radiotherapy. Ionizing radiation (IR)-induced myelosuppression is largely attributed to the injury of hematopoietic stem and progenitor cells (HSPCs). Coriander is a culinary herb with multiple pharmacological effects and has been widely used in traditional medicine. In this study, flavonoids were identified as the main component of coriander extract with rutin being the leading compound (rutin-enriched coriander extract; RE-CE). We evaluated the radioprotective effect of RE-CE against IR-induced HSPCs injury. Results showed that RE-CE treatment markedly improved survival, ameliorated organ injuries and myelosuppression, elevated HSPCs frequency, and promoted differentiation and proliferation of HSPCs in irradiated mice. The protective role of RE-CE in hematopoietic injury is probably attributed to its anti-apoptotic and anti-DNA damage effect in irradiated HSPCs. Moreover, these changes were associated with reduced reactive oxygen species (ROS) and enhanced antioxidant enzymatic activities in irradiated HSPCs. Collectively, these findings demonstrate that RE-CE is able to ameliorate IR-induced hematopoietic injury partly by reducing IR-induced oxidative stress.

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A comprehensive overview of radiation therapy impacts of various cancer treatments and pivotal role in the immune system

Srinivasan,

Subbarayan,

Srivastava

et al. 2024

Cell Biochemistry & Function

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The cancer treatment landscape is significantly evolving, focusing on advanced radiation therapy methods to maximize effectiveness and minimize the adverse effects. Recognized as a pivotal component in cancer and disease treatment, radiation therapy (RT) has drawn attention in recent research that delves into its intricate interplay with inflammation and the immune response. This exploration unveils the underlying processes that significantly influence treatment outcomes. In this context, the potential advantages of combining bronchoscopy with RT across diverse clinical scenarios, alongside the targeted impact of brachytherapy, are explored. Concurrently, radiation treatments serve multifaceted roles such as DNA repair, cell elimination, and generating immune stress signaling molecules known as damage‐associated molecular patterns, elucidating their effectiveness in treating various diseases. External beam RT introduces versatility by utilizing particles such as photons, electrons, protons, or carbon ions, each offering distinct advantages. Advanced RT techniques contribute to the evolving landscape, with emerging technologies like FLASH, spatially fractionated RT, and others poised to revolutionize the field. The comprehension of RT, striving for improved treatment outcomes, reduced side effects, and facilitating personalized and innovative treatments for cancer and noncancer patients. After navigating these advancements, the goal is fixed to usher in a new era in which RT is a cornerstone of precision and effectiveness in medical interventions. In summarizing the myriad findings, the review underscores the significance of understanding the differential impacts of radiation approaches on inflammation and immune modulation, offering valuable insights for developing innovative therapeutic interventions that harness the immune system in conjunction with RT.

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Countering effects of a combination of podophyllotoxin, podophyllotoxin β-D-glucoside and rutin hydrate in minimizing radiation induced chromosomal damage, ROS and apoptosis in human blood lymphocytes

Cited by 10 publications

References 40 publications

Podophyllotoxin and Rutin Modulates Ionizing Radiation-Induced Oxidative Stress and Apoptotic Cell Death in Mice Bone Marrow and Spleen

Podophyllotoxin and Rutin Modulates Ionizing Radiation-Induced Oxidative Stress and Apoptotic Cell Death in Mice Bone Marrow and Spleen

Rutin-Enriched Extract from Coriandrum sativum L. Ameliorates Ionizing Radiation-Induced Hematopoietic Injury

A comprehensive overview of radiation therapy impacts of various cancer treatments and pivotal role in the immune system

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