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Original

Effects of fasting on oxidative stress in rat liver mitochondria

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Pages 339-347 | Received 04 Apr 2005, Published online: 07 Jul 2009
 

Abstract

While moderate caloric restriction has beneficial effects on animal health state, fasting may be harmful. The present investigation was designed to test how fasting affects oxidative stress, and to find out whether the effects are opposite to those previously found in caloric restriction studies. We have focused on one of the main determinants of aging rate: the rate of mitochondrial free radical generation. Different parameters related to lipid and protein oxidative damage were also analyzed. Liver mitochondria from rats subjected to 72 h of fasting leaked more electrons per unit of O2 consumed at complex III, than mitochondria from ad libitum fed rats. This increased leak led to a higher free radical generation under state 3 respiration using succinate as substrate. Regarding lipids, fasting altered fatty acid composition of hepatic membranes, increasing the double bond and the peroxidizability indexes. In accordance with this, we observed that hepatic membranes from the fasted animals were more sensitive to lipid peroxidation. Hepatic protein oxidative damage was also increased in fasted rats. Thus, the levels of oxidative modifications, produced either indirectly by reactive carbonyl compounds (Nepsilon- malondialdehyde-lysine), or directly through amino acid oxidation (glutamic and aminoadipic semialdehydes) were elevated due to the fasting treatment in both liver tissue and liver mitochondria. The current study shows that severe food deprivation increases oxidative stress in rat liver, at least in part, by increasing mitochondrial free radical generation during state 3 respiration and by increasing the sensitivity of hepatic membranes to oxidative damage, suggesting that fasting and caloric restriction have different effects on liver mitochondrial oxidative stress.

Abbreviations
ROS=

reactive oxygen species

ETC=

electron transport chain

CR=

caloric restriction

GSA=

glutamic semialdehyde

AASA=

aminoadipic semialdehyde

MDA=

malondialdehyde

MDAL=

malondialdehyde lysine

DBI=

double bond index

AA=

antimycin A

TTFA=

theonoyltrifluoroacetone

Rot=

rotenone

FRL=

free radical leak

Abbreviations
ROS=

reactive oxygen species

ETC=

electron transport chain

CR=

caloric restriction

GSA=

glutamic semialdehyde

AASA=

aminoadipic semialdehyde

MDA=

malondialdehyde

MDAL=

malondialdehyde lysine

DBI=

double bond index

AA=

antimycin A

TTFA=

theonoyltrifluoroacetone

Rot=

rotenone

FRL=

free radical leak

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