The protective effect of Podophyllum hexandrum on hepato-pulmonary toxicity in irradiated mice

Objective: Present study reports the modulatory effect of a novel formulation (G-002M), prepared from three isolated molecules of Podophyllum hexandrum rhizomes on radiation induced oxidative stress in lung and liver tissues of strain A mice. Methods: Mice, administered with G-002M formulation 1 h prior to lethal (9Gy) radiation exposure dose, were sacrificed at different time intervals. Lung and liver tissues were processed to assess the expression of extracellular superoxide dismutase (EC-SOD) by immunohistochemistry and Western blotting techniques. Histological alterations along with the biochemical determinations, using as reported markers of hepatic and lung oxidative stress were recorded. Preadministration of G-002M resulted in significant restoration of radiation induced decline in the expression of EC-SOD in both lung and liver tissues. Results: In lungs, radiation mediated histological alterations like alveolar edema, interalveolar septa thickening, inflammation and infiltration of inflammatory cells into alveolar spaces were significantly prevented by G-002M pre-treatment. Histopathological features of liver in response to radiation such as steatosis, deformed cell structure, vacuolization of the cytoplasm and injury of hepatocyte membranes were also minimized by formulation pre-treatment. The formulation could successfully inhibit radiation induced malondialdehyde (MDA) content and counter the radiation induced depletion in SOD, catalase, glutathione reductase, glutathione S-transferase and glutathione, in serum, lung and liver tissues. Radiation induced alterations in serum aspartate aminotransferase, alanine tranaminase, cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, alkaline phosphatase, total protein, albumin and lactate dehydrogenase were maintained by G-002M pre-treatment. Conclusion: These results demonstrated that the bioactive phyto-constituents of Podophyllum hexandrum could significantly protect lung and liver against radiation, predominantly by reduction in lipid peroxidation and elevation of EC-SOD along with a set of endogenous defense enzymes. © 2013 GESDAV