Water soluble vitamin E (TMG) as a radioprotector

Abstract

1365-1371<span style="font-size:14.0pt;mso-bidi-font-size:8.0pt; line-height:115%;font-family:" times="" new="" roman","serif";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">Tocopherol monoglucoside (TMG), a water soluble derivative of vitamin E offers protection against deleterious effects of  ionizing radiation, both under <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">in vivo <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">and <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">in vitro <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">conditions, to biological systems. TMG was found to be a potent antioxidant and an effective free radical scavenger. It forms <span style="font-size:15.5pt; mso-bidi-font-size:9.5pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">a <span style="font-size:14.0pt; mso-bidi-font-size:8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">phenoxy<span style="font-size:14.5pt; mso-bidi-font-size:8.5pt;line-height:115%;font-family:" arial","sans-serif";="" mso-fareast-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">I <span style="font-size:14.0pt; mso-bidi-font-size:8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">radical similar to trolox upon reaction with various one-electron oxidants. TMG protected DNA from radiation-induced strand breaks. It also protected thymine glycol formation induced by gamma-radiation. Gamma-radiation-induced loss of viability of EL-tumor cells and peroxidation of lipids in microsomal and mitochondrial membranes were prevented by TMG. TMG was nontoxic to mice when administered orally up to <span style="font-size: 14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">7.0 <span style="font-size:14.0pt; mso-bidi-font-size:8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">g/kg body weight. The LD50 dose of TMG for ip administration in mice was 1<span style="font-size:14.5pt; mso-bidi-font-size:8.5pt;line-height:115%;font-family:" arial","sans-serif";="" mso-fareast-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">.15 <span style="font-size:14.0pt; mso-bidi-font-size:8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">g/kg body wt. In rats, following oral and ip administration of TMG, the absorption (distribution) half lives were <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">5.8 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">and <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">3.0 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">min respectively and elimination half  lives were <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">6.7 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">and <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">3.1 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">min respectively. Embryonic mortality resulting from exposure of pregnant mice to ionizing radiation <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%; font-family:" times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">(2 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">Gy) was reduced by <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">75% <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">by ip administration of TMG <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt; line-height:115%;font-family:" times="" new="" roman","serif";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">(0.6 <span style="font-size:14.0pt;mso-bidi-font-size: 8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">g/kg, body wt) prior to irradiation. TMG offered protection to mice against whole body gamma-radiation-induced lethality and weight loss. The LD5<span style="font-size:11.0pt; mso-bidi-font-size:5.0pt;line-height:115%;font-family:" arial","sans-serif";="" mso-fareast-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">0(30)<span style="font-size:11.0pt; mso-bidi-font-size:5.0pt;line-height:115%;font-family:" arial","sans-serif";="" mso-fareast-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"=""> <span style="font-size:14.0pt; mso-bidi-font-size:8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">of mice increased from <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">6 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">to <span style="font-size:14.5pt;mso-bidi-font-size:8.5pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">6.72 <span style="font-size:14.0pt;mso-bidi-font-size:8.0pt;line-height:115%;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">Gy upon post irradiation administration of a single dose of TMG <span style="font-size:14.5pt; mso-bidi-font-size:8.5pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">(0.6 <span style="font-size:14.0pt; mso-bidi-font-size:8.0pt;line-height:115%;font-family:" times="" new="" roman","serif";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">g/kg, body wt) by ip.</span