Modulation of Gamma Radiation-Inflicted Damage in Swiss Albino Mice by an Alcoholic Fraction of Podophyllum hexandrum Rhizome

Abstract

A partially characterized extract of Podophyllum hexandrum rhizomes was studied for its radioprotective potential in mice. A major portion of the podophyllotoxin was obtained from the extract by further fractionation. Acute toxicity and maximum tolerated dose (MTD) of a single intraperitoneal dose of the extract were studied in mice to evaluate the toxicity of the extract, if any. Radioprotective efficacy was determined in terms of survival against 10 Gy whole-body irradiation (WBI), protection against 1 Gy-induced chromosomal aberration (CA), and estimation of dose reduction factor (DRF) in irradiated and extract pretreated mice. The MTD was observed to be 60 mg/kg of body weight, whereas a dose of 90 mg/kg of body weight yielded 50% death in mice within 72 hours of intraperitoneal administration of the extract. A dose range of 15-20 mg/kg of body weight administered 2 hours before 10 Gy WBI of mice yielded 66% survival, while administration of 10-15 mg/kg of body weight of the extract 1 hour before WBI yielded more than 90% survival. A DRF of 1.625 was estimated for 10 and 15 mg/kg of body weight of the extract administered 1 hour before WBI. Further studies on modulation of 1 Gy-induced CA revealed significant radioprotective efficacy of the extract in mouse bone marrow cells. Partial removal of podophyllotoxin was useful in reducing toxicity of the extract without altering its radioprotective efficacy.

Normal Tissue Protectors Against Radiation Injury

“…The effective radioprotective dose for P. hexandrum extract is well below the maximum tolerable dose 54 and both intraperitoneal and intramuscular routes have been demonstrated to impart significant radioprotection, at least in animal models. An extract prepared from the berries of Hippophae rhamnoides has shown similar (> 90 %) survival in mice with lethal WBI 56,57 . It protected DNA in vitro 58,59 , reduced bone marrow cytogenetic damage 60 , scavenged radiation and chemical-induced free radicals 55 , reduced cytotoxicity in cultured cells 61 .…”

Ethnopharmacology, phytochemistry and cytotoxicity of emerging biotechnological tool: Mayapple (Podophyllum hexandrum L.: Berberidaceae)

“…hexandrum also has a radioprotective potential exerted by its rhizome. The radioprotective property of this plant at molecular level along with expression of the patterns of the various proteins associated with apoptosis in the spleen of male Swiss albino mice by immunoblotting were reported by some researchers [34][35][36][37][38][39][40][41]. The radioprotective activities of this plant are used widely.…”

Stress-Mediated Adaptive Response Leading to Genetic Diversity and Instability in Metabolite Contents of High Medicinal Value: An Overview onPodophyllum hexandrum

“…The DRF of various preparations of P. hexandrum, calculated based on the available formula (Miller and Tainter, 1944), has been documented as 1.3-1.60 depending on the extract used (Gupta et al, 2007(Gupta et al, , 2008Sankhwar et al, 2009). P. hexandrum preparations have shown highly significant difference in MTD, LD 50 , LD 100 , and therapeutic doses (Gupta et al, 2007(Gupta et al, , 2008(Gupta et al, , 2009).…”

“…The DRF of various preparations of P. hexandrum, calculated based on the available formula (Miller and Tainter, 1944), has been documented as 1.3-1.60 depending on the extract used (Gupta et al, 2007(Gupta et al, , 2008Sankhwar et al, 2009). P. hexandrum preparations have shown highly significant difference in MTD, LD 50 , LD 100 , and therapeutic doses (Gupta et al, 2007(Gupta et al, , 2008(Gupta et al, , 2009). More than 90% whole-body protection against nil survival in lethally irradiated mice by various preparations of this herb has proven this plant could be highly useful during accidental radiation exposure scenario (Gupta et al, 2007(Gupta et al, , 2008(Gupta et al, , 2009.…”

“…P. hexandrum preparations have shown highly significant difference in MTD, LD 50 , LD 100 , and therapeutic doses (Gupta et al, 2007(Gupta et al, , 2008(Gupta et al, , 2009). More than 90% whole-body protection against nil survival in lethally irradiated mice by various preparations of this herb has proven this plant could be highly useful during accidental radiation exposure scenario (Gupta et al, 2007(Gupta et al, , 2008(Gupta et al, , 2009.…”