Depletion of liver glutathione potentiates the oxidative stress and decreases nitric oxide synthesis in a rat endotoxin shock model.
OBJECTIVE
To verify the effects of liver glutathione depletion on redox status and nitric oxide system in a rat endotoxic shock model.


METHODS
Prospective, randomized, controlled study on rats.


METHODS
A cardiocirculatory research laboratory.


METHODS
A total of 28 Sprague-Dawley male rats (200-250 g body weight) were divided into four experimental groups.


METHODS
Arterial blood, liver, and lung samples were taken from each animal under sodium pentobarbital (40 mg/kg i.p.) anesthesia 4 hrs after lipopolysaccharide (LPS group: 5 mg/kg i.p.; n = 7) or vehicle (control group: isotonic NaCl sterile solution i.p.; n = 7) treatments. Phorone (250 mg/kg i.p.) was injected to deplete glutathione in another two experimental groups of rats 30 mins before LPS (phorone+LPS group; n = 7) or vehicle (phorone group; n = 7) treatments, and 4 hrs later the same samples as in LPS and control groups were taken under anesthesia.


RESULTS
Compared with the control group, the LPS group presented higher plasma concentration of end products of nitric oxide metabolism nitrites/nitrates, higher lung activity of inducible nitric oxide synthase, and oxidative stress defined by increased plasma concentration of the lipid peroxides malonaldehyde and 4-hydroxynonenal, and decreased plasma total antioxidant capacity. Treatment with phorone depleted liver glutathione (80% to 90%). In the liver glutathione-depleted animals, the oxidative stress induced by LPS was potentiated and blunted the increases in inducible nitric oxide synthase and plasma nitrites/nitrates.


CONCLUSIONS
These results show that depletion of the liver glutathione increases the oxidative stress and decreases nitric oxide synthesis of LPS-induced shock in rats.
Carbonell
L F
LF
Department of Physiology, Faculty of Medicine, University of Murcia, Spain.
Nadal
J A
JA
Llanos
M C
MC
Hernández
I
I
Nava
E
E
Díaz
J
J
D000818:Animals; D005978:Glutathione / Q000172:deficiency*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000378:metabolism*
D009569:Nitric Oxide; D005978:Glutathione