Mitigation of whole-body gamma radiation–induced damages by Clerodendron infortunatum in mammalian organisms

Abstract

Several phytoceuticals and extracts of medicinal plants are reported to mitigate deleterious effects of ionizing radiation. The potential of hydro-alcoholic extract of Clerodendron infortunatum (CIE) for providing protection to mice exposed to gamma radiation was investigated. Oral administration of CIE bestowed a survival advantage to mice exposed to lethal doses of gamma radiation. Radiation-induced depletion of the total blood count and bone marrow cellularity were prevented by treatment with CIE. Damage to the cellular DNA (as was evident from the comet assay and the micronucleus index) was also found to be decreased upon CIE administration. Radiation-induced damages to intestinal crypt cells was also reduced by CIE. Studies on gene expression in intestinal cells revealed that there was a marked increase in the Bax/Bcl-2 ratio in mice exposed to whole-body 4 Gy gamma radiation, and that administration of CIE resulted in significant lowering of this ratio, suggestive of reduction of radiation-induced apoptosis. Also, in the intestinal tissue of irradiated animals, following CIE treatment, levels of expression of the DNA repair gene Atm were found to be elevated, and there was reduction in the expression of the inflammatory Cox-2 gene. Thus, our results suggest a beneficial use of Clerodendron infortunatum for mitigating radiation toxicity.

Natural Product Interventions for Chemotherapy and Radiotherapy-Induced Side Effects

“…Clerodendrum infortunatum rich in flavonoids and saponins is used in Ayurvedic and Siddha traditional medicine. Its hydro-alcoholic extract reduces radiation-induced damage to intestinal crypt cells and suppress BCL2-associated X protein (Bax)/B-cell lymphoma (Bcl-2) ratio, DNA repair gene ataxia telangiectasia mutated (ATM) and COX-2 gene in mice exposed to whole-body γ-radiation (Chacko et al, 2017 ).…”

The comet assay in animal models: From bugs to whales – (Part 2 Vertebrates)

“…Interestingly, DNA damage has been A c c e p t e d M a n u s c r i p t 20 detected not only in target organs but also in non-target organs [338]. The comet assay in rodents is also used to detect DNA damage induced by physical agents, such as ionizing γradiation [339][340][341][342], radiofrequency radiation [343][344][345], microwave radiation [346,347] and/or UV radiation [348][349][350] as well as loud noise as one of the major environmental threats to public health [351][352][353]. These studies are often performed in order to evaluate the protective potential of various natural products, e.g.…”

Cyclooxygenase‑2‑mediated upregulation of heme oxygenase 1 mitigates the toxicity of deuterium‑tritium fusion radiation

“…Additionally, the overexpression of COX-2 in NCI-H460 cells reduced the radiation sensitivity induced by gefitinib; however, no direct association was determined between the activation of ATM and expression of COX-2 ( 29 ). Chacko et al ( 30 ) determined that the hydro-alcoholic extract of Clerodendron infortunatum (CIE) reduces the total body gamma-ray radiation exposure in mice. Additionally, in the intestinal tissue of irradiated animals, following CIE treatment, the expression levels of ATM, but not its phosphorylated form, were elevated; however, the expression of COX-2 was reduced ( 30 ).…”

“…Chacko et al ( 30 ) determined that the hydro-alcoholic extract of Clerodendron infortunatum (CIE) reduces the total body gamma-ray radiation exposure in mice. Additionally, in the intestinal tissue of irradiated animals, following CIE treatment, the expression levels of ATM, but not its phosphorylated form, were elevated; however, the expression of COX-2 was reduced ( 30 ). In a previous study by Kim and Pyo ( 31 ), it was reported that treatment with the mixture of 17-AAG, an inhibitor of heat shock protein 90, and celecoxib, an inhibitor of COX-2, increased the sensitivity of various human cancer cells to radiation through downregulating ATM and ATR ( 31 ).…”