Protective Effects of N-acetylcysteine and a Prostaglandin E1 Analog, Alprostadil, Against Hepatic Ischemia: Reperfusion Injury in Rats

Abstract

Ischemia-reperfusion (I/R) injury has a complex pathophysiology resulting from a number of contributing factors. Therefore, it is difficult to achieve effective treatment or protection by individually targeting the mediators or mechanisms. Our aim was to analyze the individual and combined effects of N-acetylcysteine (NAC) and the prostaglandin E1 (PGE1) analog alprostadil on hepatic I/R injury in rats. Thirty male Sprague-Dawley rats were randomly divided into five groups (six rats per group) as follows: Control group, I/R group, I/R + NAC group, I/R + alprostadil group, and I/R + NAC + alprostadil group. The rats received injections of NAC (150 mg/kg) and/or alprostadil (0.05 μg/kg) over a period of 30 min prior to ischemia. These rats were then subjected to 60 min of hepatic ischemia followed by a 60-min reperfusion period. Hepatic superoxide dismutase (SOD), catalase, and glutathione levels were significantly decreased as a result of I/R injury, but they were increased in groups treated with NAC. Hepatic malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) activities were significantly increased after I/R injury, but they were decreased in the groups with NAC treatment. Alprostadil decreased NO production, but had no effect on MDA and MPO. Histological results showed that both NAC and alprostadil were effective in improving liver tissue morphology during I/R injury. Although NAC and alprostadil did not have a synergistic effect, our findings suggest that treatment with either NAC or alprostadil has benefits for ameliorating hepatic I/R injury.

Keywords: Alprostadil; Ischemia–reperfusion; N-acetylcysteine; Prostaglandin E1 analog.

Figure 1

Effects of ischemia–reperfusion (I/R) and pretreatment with NAC and/or alprostadil on (a) catalase, (b) superoxide dismutase, (c) glutathione, and (d) malondialdehyde levels in liver tissues. Procedures are described in Materials and Methods. *P< 0.05 as compared with the I/R group

Figure 2

Effects of ischemia–reperfusion (I/R) and pretreatment with NAC and/or alprostadil on (a) myeloperoxidase and (b) nitric oxide levels in liver tissue. Procedures are described in Materials and Methods. *P< 0.05 as compared with the I/R group

Figure 3

Liver histological analysis. In the control group, normal liver parenchyma cells appear with hepatocytes and sinusoids around the central vein and show regular morphology. In the I/R group, hepatocytes are prominently swollen with marked vacuolization (*). Congestion (+) is noted in enlarged sinusoids. The liver parenchyma cells accompanied by hepatocytes and sinusoids around the central vein show irregular morphology. In the I/R + NAC group, the I/R + alprostadil group, and the I/R + NAC + alprostadil group, hepatocytes and sinusoids are present with normal morphology reflecting well-preserved liver parenchyma cells. The scale bars represent 50 μm. (H and E, ×400)