An Experimental Study on the Protective Role of Aminoguanidine on Liver Injury in Endotoxic Shock_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SONG Wenzhe ¹ , SONG Yan ¹ , TAN Yan ² , YIN Jiajun ¹

Department of General Surgery, The ChinaJapan Union Hospital, Jilin University, Changchun 130031, China;

Corresponding author：

Keywords：

Aminoguanidine; Endotoxic shock; Mitochondrion; Nitric oxide; Liver

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ObjectiveTo study the effects of aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS) on the pathological changes of liver tissues and ultrastructural changes of liver cells in rodent model of endotoxic shock. MethodsTwentyfour male Wistar rats were randomly divided into normal control group，lipopolysaccharide (LPS) control group and AG treatment group, each group had 8 rats. Rats were challenged by E.coli LPS to set up the model of endotoxic shock, AG group were treated by aminoguanidine. The pathological and ultrastructural changes of liver tissues and plasma NO contents of three groups were observed and compared. ResultsLight microscopy revealed that many tiny abscesses scattered in liver tissue in LPS group, accompanied by necrosis of liver cells and neutrophils infiltration, while liver injuries of AG group were much slighter than that in LPS group. Electron microscopy revealed that there were dissolved plaques in hepatocyte nuclears, swelling of mitochondria, decreasing in number of mitochondrial ridges, while AG play a protective role to nuclears and mitochondria of hepatocytes. The plasma NO levels of LPS control group were higher than that of normal control group, and plasma NO levels decreased significantly after AG treatment, but still higher than that of normal control group. Conclusion Aminoguanidine selectively inhibits iNOS activity and prevents the overproduction of NO induced by iNOS, thus attenuates the damages of liver structure induced by NO. This method has potential value in clinical application, which deserves more deep research.

Citation： SONG Wenzhe,SONG Yan,TAN Yan,YIN Jiajun. An Experimental Study on the Protective Role of Aminoguanidine on Liver Injury in Endotoxic Shock. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2003, 10(4): 347-350. doi: Copy

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1. Ruetten H, Southan GJ, Abate A, et al. Attenuation of endotoxininduced multiple organ dysfunction by 1amino2hydroxyguanidine, a potent inhibitor of inducible nitric oxide synthase [Ｊ]. Br J Pharmacol, 1996； 118(2)∶261.
2. Witte K, Schnecko A, Zuther P, et al. Contribution of the nitric oxideguanylyl cyclase system to circadian regulation of blood pressure in normotensive WistarKyoto rats [Ｊ]. Cardiovasc Res, 1995； 30（5）∶682.
3. Yang F, Comtois AS, Fang L, et al. Nitric oxidederived nitrate anion contributes to endotoxic shock and multiple organ injury/dysfunction [Ｊ]. Crit Care Med, 2002； 30(3)∶650.
4. Moncada S, Higgs A. The Largininenitric oxide pathway [Ｊ]. N Eng J Med, 1993； 329(27)∶2002.
5. Thiemermann C .The role of the Larginine： nitric oxide pathway in circulatory shock [Ｊ]. Adv Pharmacol, 1994； 28（1）∶45.
6. Brealey D, Brand M, Hargreaves I, et al. Association between mitochondrial dysfunction and severity and outcome of septic shock [Ｊ]. Lancet, 2002； 360(9328)∶219.
7. Morris SM Jr, Billiar TR. New insights into the regulation of inducible nitric oxide synthesis [Ｊ]. Am J Physiol, 1994； 266（6 Pt 1）∶E829.
8. Billiar TR, Curran RD, Stuehr DJ, et al. An Largininedependent mechanism mediates Kupffer cell inhibition of hepatocyte protein synthesis in vitro [Ｊ]. J Exp Med, 1989； 169(4)∶1467.
9. Nathan C. Nitric oxide as a secretory product of mammalian cells [Ｊ]. FASEB J, 1992； 6(12)∶3051.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

An Experimental Study on the Protective Role of Aminoguanidine on Liver Injury in Endotoxic Shock

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