Effects of isoflurane, pentobarbital, and urethane on apoptosis and apoptotic signal transduction in rat kidney.
BACKGROUND
Renal cell apoptosis contributes significantly to the pathogenesis of acute renal failure. Anesthetic agents have been shown to modulate apoptotic signal transduction in various tissues. We examined the effects of 6 h of different general anesthetic techniques on renal cell apoptosis in rat kidneys.


METHODS
Twenty-one male Sprague-Dawley rats were randomly allocated into four groups: (i) control, non-anesthetized rats (n= 3) and rats anesthetized with (ii) inhaled isoflurane (n= 6), (iii) intraperitoneal pentobarbital (n= 6), and (iv) intraperitoneal urethane (n= 6). Animals were sacrificed 6 h after the induction of anesthesia.


RESULTS
Apoptosis was assessed by terminal deoxynucleotidyl transferase-fluorescein end-labeling analysis. RNA was extracted from the left kidney to probe cDNA microarrays. Gene expression was measured as a percentage of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and subsequently confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with the control (no anesthesia), urethane significantly (P < 0.001) induced apoptosis in both the renal cortex and medulla. Isoflurane significantly (P < 0.001) inhibited apoptosis in the medulla. Microarray analysis revealed that urethane up-regulated more (74) genes than pentobarbital (16) and isoflurane (10). Isoflurane down-regulated more genes (85) than pentobarbital (74) and urethane (12). These anesthetic-induced modulations were significant (P < 0.05) for 60 isoflurane-, 30 pentobarbital- and 4 urethane-modulated genes.


CONCLUSIONS
Our results suggest that general anesthetic drugs have an effect on renal cell apoptosis and apoptotic signal transduction, and thus may potentially affect the risk of subsequent acute renal failure.
Aravindan
N
N
Division of Anesthesiology and Critical Care, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. naravind@ouhsc.edu
Cata
J P
JP
Hoffman
L
L
Dougherty
P M
PM
Riedel
B J
BJ
Price
K J
KJ
Shaw
A D
AD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D017931:DNA Primers; D007530:Isoflurane / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014520:Urethane / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics
D017931:DNA Primers; D051028:bcl-2-Associated X Protein; D014520:Urethane; D007530:Isoflurane; D010424:Pentobarbital