ORIGINAL ARTICLE Protective effects of N-acetylcysteine on myocardial injury induced by hindlimb ischaemia–reperfusion: a histological study in a rat model Mohammad Ashrafzadeh Takhtfooladi & Gholamreza Jahanshahi & Amir Sotoudeh & Amirali Jahanshahi Received: 21 January 2013 / Accepted: 16 May 2013 / Published online: 28 May 2013 # Springer-Verlag London 2013 Abstract This study evaluated the effects of N-acetylcysteine as a scavenger of radical oxygen species on myocardial injury as a remote organ after skeletal muscle ischaemia–reperfusion. Twenty male Wistar rats were allocated randomly into two experimental groups: ischaemia–reperfusion and ischaemia– reperfusion+ N-acetylcysteine. All animals underwent 2 h of ischaemia by occlusion of the femoral artery followed by 24 h of reperfusion. Rats treated with N-acetylcysteine were given an intravenous dose of 150 mg/kg, immediately before reper- fusion. After the reperfusion period, animals were euthanized and hearts harvested for histopathological analysis under light microscopy. In the ischaemia–reperfusion group, tissues showed histological changes with interstitial oedema, neutro- phil infiltration and adhesion of neutrophils to the endothelium, haemorrhage and coagulative necrosis. Histopathologically, there was a significant difference (P <0.05) between the two groups. The administration of N-acetylcysteine significantly decreased myocardial injury induced by skeletal muscle is- chaemia–reperfusion according to our histological findings. Keywords Wistar . Skeletal muscle . N-acetylcysteine . Myocardium . Histology Introduction Organ injury occurs not only during periods of ischaemia, but paradoxically also during reperfusion (Welbourn et al. 1991). This damage is collectively known as ischaemia– reperfusion injury. It is known that ischaemia–reperfusion causes remote organ injury as well as local injury. It is also seen in many other clinical scenarios, such as limb ischae- mia, organ transplantation, stroke, the gastrointestinal tract (Parks and Granger 1986) and hypovolaemic shock (Welbourn et al. 1991). Clearly ischaemia–reperfusion inju- ry is not only clinically relevant, but also very prevalent. Several mechanisms have been proposed to explain the local organ dysfunction induced by ischaemia–reperfusion; how- ever, most attention has focused on the role of reactive oxygen species and inflammatory leucocytes (Granger 1988; Granger and Korthuis 1995). Not surprisingly, oxi- dants and activated leucocytes have also been implicated as mediators of the remote organ injury induced by ischaemia– reperfusion. N-acetylcysteine has antioxidant properties and is freely filterable with a ready access to intracellular compartments (De Vries and De Flora 1993; Holodines 1991). The diver- sity of pharmacological applications of N-acetylcysteine is due mainly to the chemical properties of the cysteinyl thiol group of its molecule since the ability of reduced thiol groups to scavenge oxygen free radicals is well established (Aruoma et al. 1989; Cuzzocrea et al. 2000). Because of these properties, N-acetylcysteine is widely used in clinical practice as an antioxidant. Recently, administered N-acetylcysteine was shown to protect against ischaemia–reperfusion injuries in local and remote organs, and it was suggested that this protective effect may be due to its ability to scavenge free radicals (Cuzzocrea et al. 2000; Sotoudeh et al. 2012; Takhtfooladi M. A. Takhtfooladi (*) : A. Jahanshahi Department of Veterinary Surgery, Faculty of Specialized Veterinary Science, Science and Research Branch, Islamic Azad University, Tehran, Iran e-mail: dr_ashrafzadeh@yahoo.com G. Jahanshahi Department of Oral and Maxillofacial Pathology, School of Dentistry, Isfahan University of Medical Science, Isfahan, Iran A. Sotoudeh Faculty of Veterinary Science, Kahnooj Branch, Islamic Azad University, Kerman, Iran Comp Clin Pathol (2014) 23:1237–1240 DOI 10.1007/s00580-013-1768-7