Effects of penehyclidine hydrochloride in small intestinal damage caused by limb ischemia-reperfusion.

AIM To investigate the protective effect of penehyclidine hydrochloride post-conditioning in the damage to the barrier function of the small intestinal mucosa caused by limb ischemia-reperfusion (LIR) injury. METHODS Male Wistar rats were randomly divided into three groups (36 rats each): the sham-operation group (group S), lower limb ischemia-reperfusion group (group LIR), and penehyclidine hydrochloride post-conditioning group (group PHC). Each group was divided into subgroups (n = 6 in each group) according to ischemic-reperfusion time, i.e. immediately 0 h (T₁), 1 h (T₂), 3 h (T₃), 6 h (T₄), 12 h (T₅), and 24 h (T₆). Bilateral hind-limb ischemia was induced by rubber band application proximal to the level of the greater trochanter for 3 h. In group PHC, 0.15 mg/kg of penehyclidine hydrochloride was injected into the tail vein immediately after 3 h of bilateral hind-limb ischemia. The designated rats were sacrificed at different time-points of reperfusion; diamine oxidase (DAO), superoxide dismutase (SOD) activity, myeloperoxidase (MPO) of small intestinal tissue, plasma endotoxin, DAO, tumor necrosis factor-α (TNF-α), and interleukin (IL)-10 in serum were detected in the rats. RESULTS The pathological changes in the small intestine were observed under light microscope. The levels of MPO, endotoxin, serum DAO, and IL-10 at T₁-T₆, and TNF-α level at T₁-T₄ increased in groups LIR and PHC (P < 0.05) compared with those in group S, but tissue DAO and SOD activity at T₁-T₆ decreased (P < 0.05). In group PHC, the tissue DAO and SOD activity at T₂-T₆, and IL-10 at T₂-T₅ increased to higher levels than those in group LIR (P < 0.05); however, the levels of MPO, endotoxin, and DAO in the blood at T₂-T₆, and TNF-α at T₂ and T₄ decreased (P < 0.05). CONCLUSION Penehyclidine hydrochloride post-conditioning may reduce the permeability of the small intestines after LIR. Its protection mechanisms may be related to inhibiting oxygen free radicals and inflammatory cytokines for organ damage.

[1]  Zhen Jin,et al.  Protective effects of penehyclidine hydrochloride on liver injury in a rat cardiopulmonary bypass model , 2010, European journal of anaesthesiology.

[2]  Z. Xia,et al.  Effects of penehyclidine hydrochloride on apoptosis of lung tissues in rats with traumatic acute lung injury. , 2010, Chinese journal of traumatology = Zhonghua chuang shang za zhi.

[3]  B. Savaş,et al.  Endotoxin level in ischemia-reperfusion injury in rats: effect of glutamine pretreatment on endotoxin levels and gut morphology. , 2010, Nutrition.

[4]  Jian-xin Gan,et al.  Penehyclidine hydrochloride attenuates LPS-induced acute lung injury involvement of NF-kappaB pathway. , 2009, Pharmacological research.

[5]  Ning Wang 王宁,et al.  Relationship between transmembrane signal transduction pathway and DNA repair and the mechanism after global cerebral ischemia-reperfusion in rats , 2009, Neuroscience Bulletin.

[6]  A. García,et al.  Ketamine anesthesia reduces intestinal ischemia/reperfusion injury in rats. , 2008, World journal of gastroenterology.

[7]  T. Annecke,et al.  Effects of sevoflurane and propofol on ischaemia-reperfusion injury after thoracic-aortic occlusion in pigs. , 2007, British journal of anaesthesia.

[8]  B. Zhong,et al.  Synthesis of the optical isomers of a new anticholinergic drug, penehyclidine hydrochloride (8018). , 2005, Bioorganic & medicinal chemistry letters.

[9]  M. Teixeira,et al.  The balance between the production of tumor necrosis factor-alpha and interleukin-10 determines tissue injury and lethality during intestinal ischemia and reperfusion. , 2005, Memorias do Instituto Oswaldo Cruz.

[10]  L. Hejjel,et al.  The role of free radicals in endogenous adaptation and intracellular signals. , 2004, Experimental and clinical cardiology.

[11]  M. Teixeira,et al.  IL-1-Driven Endogenous IL-10 Production Protects Against the Systemic and Local Acute Inflammatory Response Following Intestinal Reperfusion Injury1 , 2003, The Journal of Immunology.

[12]  M. Karin,et al.  The two faces of IKK and NF-κB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion , 2003, Nature Medicine.

[13]  Marie-Luise Brennan,et al.  Myeloperoxidase Functions as a Major Enzymatic Catalyst for Initiation of Lipid Peroxidation at Sites of Inflammation* , 2002, The Journal of Biological Chemistry.

[14]  Mauro M Teixeira,et al.  Increased mortality and inflammation in tumor necrosis factor-stimulated gene-14 transgenic mice after ischemia and reperfusion injury. , 2002, The American journal of pathology.

[15]  D. Slaaf,et al.  Effects of experimental lower‐limb ischaemia–reperfusion injury on the mesenteric microcirculation , 2002, The British journal of surgery.

[16]  Q. Chen,et al.  Anisodamine protects against neuronal death following cerebral ischemia in gerbils. , 2000, Chinese medical journal.

[17]  J. Pincemail,et al.  Local and systemic consequences of severe ischemia and reperfusion of the skeletal muscle. Physiopathology and prevention. , 1998, Acta chirurgica Belgica.

[18]  T. G. Parks,et al.  Lower limb ischaemia–reperfusion injury causes endotoxaemia and endogenous antiendotoxin antibody consumption but not bacterial translocation , 1998, The British journal of surgery.

[19]  S. Ashley,et al.  Interleukin-10 reduces the systemic inflammatory response in a murine model of intestinal ischemia/reperfusion. , 1997, Surgery.

[20]  J. Stechmiller,et al.  Gut dysfunction in critically ill patients: a review of the literature. , 1997, American journal of critical care : an official publication, American Association of Critical-Care Nurses.

[21]  M. Mathru,et al.  Tourniquet‐induced Exsanguination in Patients Requiring Lower Limb Surgery: An Ischemia‐Reperfusion Model of Oxidant and Antioxidant Metabolism , 1996, Anesthesiology.

[22]  B. Rowlands,et al.  Bowel ischaemia and organ impairment in elective abdominal aortic aneurysm repair , 1995 .

[23]  I. Gartside,et al.  Prevalence of cyclic changes in limb volume (volumotion) of male patients with knee injury and the effects of ischemia/reperfusion due to tourniquet. , 1995, International journal of microcirculation, clinical and experimental.

[24]  B. Rowlands,et al.  Reduction of free radical generation minimises lower limb swelling following femoropopliteal bypass surgery. , 1994, European journal of vascular surgery.

[25]  M. Wolvekamp,et al.  Diamine oxidase: an overview of historical, biochemical and functional aspects. , 1994, Digestive diseases.

[26]  S. Kazmierczak,et al.  Evaluation of a spectrophotometric method for measurement of activity of diamine oxidase in newborn infants. , 1992, Annals of clinical and laboratory science.

[27]  C. McCollum,et al.  Lower limb ischaemia and reperfusion alters gut permeability. , 1992, European journal of vascular surgery.

[28]  P. Braquet,et al.  Superoxide dismutase (SOD) and the PAF-antagonist (BN 52021) reduce small intestinal damage induced by ischemia-reperfusion. , 1991, Free radical research communications.

[29]  C. Liu,et al.  The effects of a new cholinolytic--8018--and its optical isomers on the central muscarinic and nicotinic receptors. , 1990, Archives internationales de pharmacodynamie et de therapie.

[30]  R. Berg,et al.  Endotoxin induces bacterial translocation and increases xanthine oxidase activity. , 1989, The Journal of trauma.

[31]  K. Mullane,et al.  Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. , 1985, Journal of pharmacological methods.