Glutathione S-transferase: a potential new marker of intestinal ischemia

The accurate and early diagnosis of intestinal ischemia remains difficult chiefly because of a lack of a suitable marker that is noninvasive and easy to use. The glutathione S-transferases (GST) are a family of cytosolic enzymes involved in detoxification and released from a variety of cells when the cell membrane is damaged. The enzymes are distributed widely in the intestine and show isoform specificity in their distribution throughout the intestinal tract. Several previous reports have shown the utility of these enzymes in the diagnosis of liver and renal graft damage during and after organ transplantation. The object of this study was to determine if GST levels correlated with histologic changes of intestinal ischemia in a controlled animal model of mesenteric intestinal ischemia.

Control and experimental male Sprague-Dawley rats underwent laparotomy and ligation of the Superior Mesenteric Artery (SMA) and both control and experimental animals were studied at 30, 60, 90, 120, and 240 minutes. Blood taken from the Inferior Vena Cava (IVC) and Portal Vein (PV) and jejunal and ileal perfusates were assayed for alpha and mu isoforms of GST using a commercially available enzyme immunoassay. In addition, jejunal and ileal segments were sampled and reviewed by a histopathologist blinded to the group being studied.

A reproducible pattern of intestinal ischemia was noted with worsening grades of injury observed with greater ligation times. Luminal alpha and mu GST release (as measured by the appearance in luminal perfusate) increased with increasing ischemia times. Increased ischemia times resulted in increased levels of alpha and mu GST in both portal and systemic venous samples but lagged behind the appearance of raised luminal GST values.

The results suggest that GST may be an interesting and useful marker in the early detection of intestinal ischemia. Its detection in peripheral blood has implications for a more detailed study design to determine the sensitivity and specificity of this marker in more diverse clinical conditions such as necrotizing enterocolitis and superior mesenteric artery occlusion.