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2016 ; 38
(6
): 1683-1692
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Effect of endotoxemia in mice genetically deficient in cystathionine-?-lyase,
cystathionine-?-synthase or 3-mercaptopyruvate sulfurtransferase
#MMPMID27748832
Ahmad A
; Gerö D
; Olah G
; Szabo C
Int J Mol Med
2016[Dec]; 38
(6
): 1683-1692
PMID27748832
show ga
Hydrogen sulfide (H2S) has been proposed to exert pro- as well as
anti-inflammatory effects in various models of critical illness. In this study,
we compared bacterial lipopolysaccharide (LPS)?induced changes in inflammatory
mediator production, indices of multiple organ injury and survival in
wild?type (WT) mice and in mice with reduced expression of one of the three
H2S?producing enzymes, cystathionine-?-lyase (CSE),
cystathionine-?-synthase (CBS) or 3-mercaptopyruvate sulfurtransferase (3MST).
Mice were injected intraperitoneally (i.p.) with LPS (10 mg/kg). After 6 h, the
animals were sacrificed, blood and organs were collected and the following
parameters were evaluated: blood urea nitrogen (BUN) levels in blood,
myeloperoxidase (MPO) and malondialdehyde (MDA) in the lung, cytokine levels in
plasma and the expression of the three H2S?producing enzymes (CBS, CSE and 3MST)
in the spleen, lung, liver and kidney. LPS induced a tissue?dependent
upregulation of some of the H2S?producing enzymes in WT mice (upregulation of CBS
in the spleen, upregulation of 3MST in the liver and upregulation of CBS, CSE and
3MST in the lung). Moreover, LPS impaired glomerular function, as evidenced by
increased BUN levels. Renal impairment was comparable in the CSE?/? and ?3MST
mice after LPS challenge; however, it was attenuated in the CBS+/? mice. MPO
levels (an index of neutrophil infiltration) and MDA levels (an index of
oxidative stress) in lung homogenates were significantly increased in response to
LPS; these effects were similar in the WT, CBS+/?, CSE?/? and ?3MST mice;
however, the MDA levels tended to be lower in the CBS+/? and CSE?/? mice. LPS
induced significant increases in the plasma levels of multiple cytokines [tumor
necrosis factor (TNF)?, interleukin (IL)?1?, IL?6, IL?10, IL?12 and
interferon (IFN)?] in plasma; TNF?, IL?10 and IL?12 levels tended to be lower in
all three groups of animals expressing lower levels of H2S?producing enzymes. The
survival rates after the LPS challenge did not show any significant differences
between the four animal groups tested. Thus, the findings of this study indicate
that a deficiency in 3MST does not significantly affect endotoxemia, while a
deficiency in CBS or CSE slightly ameliorates the outcome of LPS-induced
endotoxemia in vivo.
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