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2017 ; 8
(ä): 658
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A Combination of Podophyllotoxin and Rutin Alleviates Radiation-Induced
Pneumonitis and Fibrosis through Modulation of Lung Inflammation in Mice
#MMPMID28649248
Verma S
; Kalita B
; Bajaj S
; Prakash H
; Singh AK
; Gupta ML
Front Immunol
2017[]; 8
(ä): 658
PMID28649248
show ga
Pneumonitis and pulmonary fibrosis are predominant consequences of radiation
exposure, whether planned or accidental. The present study, demonstrates
radioprotective potential of a formulation, prepared by combining podophyllotoxin
and rutin (G-003M), in mice exposed to 11?Gy thoracic gamma radiation (TGR).
Treated mice were observed for survival and other symptomatic features. Formation
of reactive oxygen species (ROS)/nitric oxide (NO) was measured in
bronchoalveolar lavage cells. DNA damage and cell death were assessed in alveolar
cells by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay.
Total protein (TP), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP)
were measured in bronchoalveolar lavage fluid (BALF)/serum of mice to assess lung
vascular permeability. Interleukin-6 (IL-6), tumor necrosis factor-? (TNF-?),
transforming growth factor-?1 (TGF-?1), cluster of differentiation 45, inducible
nitric oxide synthase (iNOS), and nitrotyrosine were also estimated in lungs/BALF
of differentially treated mice. Our observations revealed 100% survival in
G-003M-pretreated mice against 66.50% in 11?Gy TGR exposed. Other symptoms like
reduction in graying of hair, weight loss, and breathing rate were also observed
in pretreated groups. Significant decline in ROS/NO and cell death in formulation
pretreated mice were also observed. Decreased level of TP, LDH, and ALP in
BALF/serum samples revealed G-003M-induced inhibition in lung permeability. Level
of IL-6, TNF-?, and TGF-?1 in the lungs of these mice was found corresponding to
control group at 8?weeks posttreatment. On the contrary, these cytokines raised
significantly in 11?Gy TGR-exposed mice. Lung pneumonitis and fibrosis were found
significantly countered in these mice. The observations revealed that G-003M
could regulate immune system by curtailing radiation-induced oxidative and
inflammatory stress, which has helped in minimizing radiation-inflicted
pneumonitis and fibrosis.