Free radical scavenging and radioprotective activity of dehydrozingerone against whole body gamma irradiation in Swiss albino mice.
Dehydrozingerone (DZ) was explored for in vitro-in vivo antioxidant potential and in vivo radioprotective activity against whole body gamma irradiation in Swiss albino mice. DZ scavenged the ABTS (2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) and DPPH (1, 1-dipehnyl-2-picrylhydrazyl) free radicals at room temp. DZ reduced Fe (III) to Fe (II) at pH 7.4 and scavenged the NADH/phenazine methosulfate generated superoxide radical in cell free system. DZ also scavenged the nitric oxide radical generated by sodium nitroprusside. To evaluate the radioprotective activity, mice were exposed to whole body gamma irradiation 30 min after the drug treatment at a dose rate of 1.66 Gy/min. Pretreatment with DZ 75, 100 and 125 mg/kg, i.p. reduced the radiation induced mortality and increased the mean survival times (MSTs). An i.p. dose of DZ 100 mg/kg was found the most effective dose in preventing radiation sickness and increasing the MST. Pretreatment DZ100 mg/kg maintained the spleen index (spleen weight/body weight x 100) and stimulates the endogenous spleen colony forming units (CFU). Pretreatment with DZ100 mg/kg maintained the villus height close to normal, prevents mucosal erosion and basement membrane damage in irradiated mice jejunum. However, no significant reductions in dead, inflammatory and mitotic cells were observed in DZ pretreated mice, but there was an increased in crypt cells proliferation and regeneration. Pretreatment with DZ100 mg/kg significantly elevated the endogenous antioxidant enzymes (GSH, GST and SOD) in mice at 2, 4 and 8 h post sham irradiation. Radiation induced fall in endogenous antioxidant enzymes was significantly prevented by DZ pretreatment. Pretreatment with DZ 75 and 100 mg/kg reduced the radiation induced micronucleated polychromatic erythrocytes (MPCE) and normochromatic erythrocytes (MNCE) in mice bone marrow. DZ also maintained the polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) ratio (P/N ratio) in irradiated mice. Dose modifying factor (DMF) was calculated by using the graded radiation dose (8.0, 9.0, 9.5 and 10 Gy). DZ 100 mg/kg elevated radiation LD(50) from 9.1 to 10.0 Gy, indicating the DMF of 1.09.
Parihar
Vipan Kumar
VK
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal, India.
Dhawan
Jatin
J
Kumar
Suryakant
S
Manjula
S N
SN
Subramanian
G
G
Unnikrishnan
M K
MK
Rao
C Mallikarjuna
CM
D000818:Animals; D052160:Benzothiazoles / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D015162:Micronucleus Tests; D009569:Nitric Oxide / Q000378:metabolism; D010627:Phenethylamines / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013343:Styrenes / Q000494:pharmacology*; D013451:Sulfonic Acids / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D016019:Survival Analysis; D014916:Whole-Body Irradiation
D052160:Benzothiazoles; D016166:Free Radical Scavengers; D010627:Phenethylamines; D011837:Radiation-Protective Agents; D013343:Styrenes; D013451:Sulfonic Acids; D013481:Superoxides; C057485:1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D009569:Nitric Oxide; C052933:methyl-3-methoxy-4-hydroxystyryl ketone; D002374:Catalase; D005982:Glutathione Transferase; D005978:Glutathione