الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
The present study is conducted to investigate the possible curative effect of the gas transmitter, H2S, in acetaminophen-induced hepatotoxicity in mice. N-Acetyl cysteine, a well established therapeutic antidote, was used as a positive control drug.
The curative effect of sodium hydrogen sulfide, an H2S donor, in acetaminophen-induced hepatotoxicity in mice was evaluated by measuring serum alanine aminotransferase as well as histopathological study 4 h after acetaminophen administration. The effects of investigated drugs on the oxidative stress parameters (hepatic malondialdehyde, reduced glutathione and catalase levels) were also investigated. In addition, hepatic nitric oxide content as well as immunohistochemical study for tumor necrosis factor-α and cyclooxygenase-2 expression were performed. Hence the KATP channel was demonstrated to mediate some actions of H2S; second set of experiments was designed to investigate the effect of coadministration of glibenclamide, KATP blocker, on the examined curative effect of sodium hydrogen sulfide by assessing serum alanine aminotransferase as well as histopathological study.
The results of the current study revealed that acetaminophen administration (650 mg/kg i.p.) significantly increased serum level of alanine aminotransferase indicating damage of hepatocytes. Sodium hydrogen sulfide treatment (3 mg/kg i.p.) produced comparable results with N-acetyl cysteine (1200 mg/kg i.p.). It almost normalized the alanine aminotransferase level.
The light microscopic pictures were in harmony with results of alanine aminotransferase. The hepatic lobules showed centrilobular necrosis and inflammatory cell infiltration with dilated congested central vein in acetaminophen treated-mice. Treatment with sodium hydrogen sulfide significantly improved the microscopic picture. It preserved the hepatic architecture, reduced infiltration by inflammatory cell.
Assessment of oxidative stress parameters revealed elevation of malondialdehyde, the marker of lipid peroxidation, and depletion of reduced glutathione in liver of acetaminophen treated-mice indicating oxidative damage. Acetaminophen also caused significant elevation of hepatic nitric oxide content in the form of nitrites and nitrates.
Sodium hydrogen sulfide treatment led to reduction in oxidative stress as evidenced by decrease in malondialdehyde level and replenishment the glutathione stores in liver. It also significantly reduced the hepatic nitric oxide content. This effect also contributed in impeding the oxidative damage.
Immunohistochemical study of liver tissue showed that acetaminophen induced marked expression of the proinflammatory tumor necrosis factor-α and the cyclooxygenase-2, a proposed anti-inflammatory mediator. Sodium hydrogen sulfide treatment markedly reduced tumor necrosis factor-α expression, while cyclooxygenase-2 expression was markedly enhanced with nuclear translocation into hepatocytes. The results obtained by sodium hydrogen sulfide treatment were similar to results produced by the reference drug.
Results of the second set of experiments indicated that glibenclamide did not abolish the curative effect of sodium hydrogen sulfide. This was evidenced by observing no significant difference in serum alanine aminotransferase as well as histopathological study between administration of sodium hydrogen sulfide alone or concurrently with glibenclamide in acetaminophen-induced hepatotoxicity in mice.
from the above data, it is clear that hydrogen sulfide was able to treat the liver from the toxicant effect of acetaminophen at least in part through amelioration of oxidative damage, decreasing tumor necrosis factor-α expression and up regulation with nuclear translcation of cyclooxygenase-2 which posses diverse hepatoprotective effects. However, the lack of glibenclamide effect pushed us for suggestion that KATP had no role in the curative effect of H2S.
It is fairly to mention that one study is not capable of interpreting the hepatic curative effect for such gas, with multiple mechanisms and diverse actions that are not completely elucidated till now. Thus, other possible mechanisms can not be ruled out and further studies are still required to clarify this point.
In conclusion, the results of present study demonstrated the curative effect of H2S against acetaminophen-induced hepatotoxicity in mice. The antioxidant effect of H2S was evident in this study. The newly emerging role of H2S, an up regulation and nuclear translocation of the anti-inflammatory cyclooxygenase-2 was also implicated in the hepatic curative effect. At last, the comparable results of H2S with N-acetyl cysteine is encouraging to suggest H2S as a treatment in acetaminophen hepatotoxicity. However further experimental studies are still needed for more details about H2S as a drug.