Time- and dose-dependent differential regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase enzymatic activity and mRNA level by vitamin E in rat blood cells.
BACKGROUND
Vitamin E is the most important lipid-soluble antioxidant. Recently, it has been proposed as a gene regulator, and its gene modulation effects have been observed at different levels of gene expression and cell signaling. This study was performed to investigate  the effects of vitamin E on the activity and expression of the most important endogenous antioxidant enzyme, superoxide dismutase (SOD), in rat plasma.


METHODS
Twenty-eight male Sprauge-Dawley rats were divided into four groups: control group and three dosing groups.  The control group received the vehicle (liquid paraffin), and the dosing groups received twice-weekly intraperitoneal injections of 10, 30, and 100 mg/kg of vitamin E ((±)-α-Tocopherol) for 6 weeks. Quantitative real-time reverse transcription-polymerase chain reaction and  enzyme assays were used to assess the levels of Cu/Zn-SOD and Mn-SOD mRNA and enzyme activity levels in blood cells at 0, 2, 4, and 6 weeks following vitamin E administration. Catalase enzyme activity and total antioxidant capacity were also assessed in plasma at the same time intervals.


RESULTS
Mn-SOD activity was significantly increased in the 100 and 30 mg/kg dosing groups after 4 and 6 weeks, with corresponding significant increase in their mRNA levels. Cu/Zn-SOD activity was not significantly changed in response to vitamin E administration at any  time points, whereas Cu/Zn-SOD mRNA levels were significantly increased after longer time points with high doses (30 and 100 mg/kg) of vitamin E. Catalase enzyme activity was transiently but significantly increased after 4 weeks of vitamin E treatment in 30 and 100 mg/kg dosing groups.  Total antioxidant status was significantly increased after 4 and 6 weeks in the 100 mg/kg dosing group.


CONCLUSIONS
Only the chronic administration of higher doses of alpha-tocopherol is associated with the increased activity and expression of Mn-SOD in rats. Cu/Zn-SOD  activity and expression does not dramatically change in response to vitamin E.
\Department of Biochemistry, Tehran University of Medical Sciences, Tehran, Iran.
Maliheh
M
Hajiani
Farideh
F
Razi
Aboualfazl
A
Golestani
Mehdi
M
Frouzandeh
Ali Akbar
AA
Owji
Shahnaz
S
Khaghani
Naghmeh
N
Ghannadian
Ahmad
A
Shariftabrizi
Parvin
P
Pasalar
D000818:Animals; D000975:Antioxidants / Q000032:analysis; D001773:Blood Cells / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D057075:Enzyme Assays; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D008899:Mineral Oil / Q000008:administration & dosage; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013482:Superoxide Dismutase / Q000097:blood* / Q000235:genetics; D013997:Time Factors; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; D012333:RNA, Messenger; D008899:Mineral Oil; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol