Non-steroidal anti-inflammatory drugs and apoptosis in the gastrointestinal tract: potential role of the pentose phosphate pathways

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely pr escribed drugs, primarily for treatment of arthritis. NSAIDs can have two e ffects independent of their anti-inflammatory action. Tn the stomach and sm all bowel long term NSAID consumption can lead to ulceration, whereas in th e colon NSAID use can regress existing tumours. In this review, we hypothes ise that NSAID-induced damage occurs predominantly by promoting apoptosis, involving a number of mechanisms depending on the type and the redox state of the cell. In addition to inhibiting cyclooxygenase (COX) activity, this includes interfering with glucose metabolism through both arms of the pento se phosphate pathways and energy production via glycolysis and oxidative ph osphorylation. Shifting the cellular balance from proliferation to apoptosi s is probably the most important outcome by which NSAIDs exhibit their diff ering actions. Understanding how these different pathways can be reconciled and their contribution to the balance between cell birth and cell death is the challenge for the future. The pentose phosphate pathways may provide a pivotal point for understanding links between factors which alter prolifer ative activity (e.g. COXs), provide energy metabolism (particularly aerobic and anaerobic metabolism of glucose), and change the redox state of the ce ll leading to apoptosis. (C) 2000 Elsevier Science B.V. All rights reserved .