Protection of the Hemopoietic System by Podophyllum hexandrum against Gamma Radiation-Induced Damage

Abstract

A semi-purified extract of low-altitude Podophyllum hexandrum (REC-2001) containing a relatively low content of podophyllotoxin (3.25 %) exhibited potent antioxidant ability in lipid media (at 1000 μg/mL against 0.25 kGy) and significant (p < 0.05) hydroxyl ion scavenging potential (78.83 % at 500 μg/mL). In vitro investigations revealed the ability of REC-2001 to significantly (p < 0.05) reduce radiation-induced hemolysis (2 μg/mL; 46.184 %) and nitric oxide scavenging levels (IC₅₀: 792 ± 1.25 μg/mL). Protection of the hemopoietic system of Strain ‘A’ mice administered 20 mg/kg BW REC-2001 30 min prior to lethal irradiation (10 Gy) was recorded and was mediated by free radical scavenging and lowering of lipid oxidation. Further studies investigating the effects of REC-2001 on stem cell modulation are warranted.

Radioprotection - hemopoietic system - antioxidant - Podophyllum hexandrum - Podophyllotoxin - lignan glycoside

References

• 1 Coleman N E, Blakely W F, Fike J R. Molecular and cellular biology of moderate-dose (1 - 10 Gy) radiation and potential mechanisms of radiation protection: Report of a workshop (Bethesda, Maryland, USA, December 17 - 18, 2001).  Radiat Res. 2003;  159 812-34
• 2 Thomson J F. Radiation protection in mammals. New York; Reinhold 1962
• 3 Prasad K N. Modification of cellular radiation damage.  In: Handbook of Radiobiology. 2nd Edition New York; CRC Press 1995: p. 61-89
• 4 Bump A, Malaker K. The mechanism of radiation protection by non-protein sulfhydryls: glutathione, cysteine and cysteamine.  In: Radioprotectors chemical, biological, and clinical perspectives. Edward A, editor Boca Raton; CRC Press 1997: p. 25-52
• 5 Floersheim G L. Calcium antagonists protect against lethal doses of ionizing radiation.  Br J Radiol. 1992;  65 1025-9
• 6 Behling U H. The radioprotective effect of bacterial endotoxin.  In: Beneficial effects of endotoxin. Nowotry A, editor New York; Plenum Press 1983: p. 127
• 7 Patchen M L, Mac Vittie T J. Hemopoietic effects of intravenous soluble glucan administration.  J Immunopharmacol. 1986;  8 407-25
• 8 Neta R, Oppenheim J J, Ledney G D. Role of cytokines in innate and LPS-enhanced radioresistance.  In: Radiation research: a twentieth-century perspective. Dewey WC, Edington M, Fry RJM, Hall EJ, Whitmore GF, editors San Diego; Academic Press; 1992: p. 830
• 9 Milenkovic P, Ivanovic Z, Stosic-Grujicic S. The in vivo effect of recombinant human interleukin-1 receptor antagonist on spleen colony forming cells after radiation induced myelosuppression.  Eur Cytokine Netw. 1995;  6 177-80
• 10 Gardner R V, McKinnon E, Poretta C, Leiva L. Hemopoietic function after use of IL-1 with chemotherapy or irradiation.  J Immunol. 2003;  171 1202-6
• 11 Arora R, Gupta D, Chawla R, Sagar R, Sharma A K, Prasad J. et al . Radioprotection by plant products: present status and future prospects.  Phytother Res. 2005;  19 1-22
• 12 Song J Y, Han S K, Bae K G, Lin D S, Son S J, Jung I S. et al . Radioprotective effects of ginsan on immunomodulation.  Radiat Res. 2003;  159 744-68
• 13 Singh J, Shah N C. Podophyllum: A review.  Curr Res Med Aromat Plants. 1994;  16 53-83
• 14 Botta B, Delle Monache G, Misiti D, Vitali A, Zappia G. Aryltetralin lignan: chemistry, pharmacology and biotransformations.  Curr Med Chem. 2001;  8 1363-81
• 15 Giri A, Narasu M L. Production of podophyllotoxin from Podophyllum hexandrum: a potential natural product for clinically useful anticancer drugs.  Cytotechnology. 2000;  34 17-26
• 16 Gupta D, Arora R, Garg A P, Goel H C. Radiation protection of HepG2 cells by Podophyllum hexandrum .  Mol Cell Biochem. 2003;  250 25-40
• 17 Asamari A M, Addis P B, Epley R J, Krick T P. Wild rice hull antioxidants.  J Agric Food Chem. 1996;  44 126-30
• 18 Halliwell B, Gutteridge J MC, Aruoma O I. The deoxyribose method: A simple test tube assay for determination of the rate constants for reactions of hydroxyl radicals.  Anal Biochem. 1987;  165 215-9
• 19 Green L C, Wagner D A, Glogowski J. Analysis of nitrate, nitrite and nitrate in biological fluids.  Anal Biochem. 1982;  126 131-8
• 20 Srour M A, Bitto Y Y, Juma M, Irhimeh M R. Exposure of human erythrocytes to oxygen radicals causes loss of deformability, increased osmotic fragility, lipid peroxidation and protein degradation.  Clin Hemorheol Microcircul. 2000;  23 13-21
• 21 Chawla R, Arora R, Kumar R, Sharma A K, Prasad J, Singh S. et al . Antioxidant activity of fractionated extracts of rhizomes of high altitude Podophyllum hexandrum: Role in radiation protection.  Mol Cell Biochem. 2005;  273 193-208
• 22 Arouma O I, Grootveld M, Halliwell B. The role of iron in ascorbate dependent deoxyribose degradation: evidence consistent with site specific hydroxyl radical generation caused by iron ions bound to deoxyribose molecule.  J Inorg Biochem. 1987;  29 289-99
• 23 Kumar P I, Goel H C. Iron chelation and related properties of Podophyllum hexandrum, a possible role in radioprotection.  Indian J Exp Biol. 2000;  38 1003-6
• 24 Pugh N I, Khan I, Moraes R M, Pasco D. Podophyllotoxin lignans enhance IL-1E but suppress TNF-α mRNA expression in LPS-treated monocytes.  Immunopharmacol Immunotoxicol. 2001;  23 83-95
• 25 Gupta D, Arora R, Garg A P, Goel H C. Radiation protection of mitochondrial system by Podophyllum hexandrum Royale in-vivo .  Mol Cell Biochem. 2004;  266 65-77
• 26 Middleton E J, Kandaswami C, Theoharides T C. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer.  Pharmacol Rev. 2000;  52 673-751
• 27 Kitts D D, Wijewickreme A N, Hu C. Antioxidant properties of a North American ginseng extract.  Mol Cell Biochem. 2000;  203 1-10
• 28 Arora R, Chawla R, Sagar R, Prasad J, Singh S, Kumar R. et al .Evaluation of radioprotective activities of Rhodiola imbricata Edgew - A high altitude plant. Mol Cell Biochem 2005: 209-23
• 29 Cassarett A P. Radiation Biology. New Jersey; Prentice-Hall Inc. England Cliffs 1968
• 30 Goel H C, Prasad J, Singh S, Sagar R K, Agrawala P K, Sinha A K. et al . Radioprotective potential of a herbal extract of Tinospora cordifolia .  J Radiat Res. 2004;  45 61-8