Drug-induced enteropathy

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed medications for treatment of inflammatory and pain-related conditions. However, their use is associated with a broad spectrum of adverse reactions, including upper gastrointestinal (GI) adverse effects, such as dyspepsia, heartburn, and abdominal discomfort, as well as more serious events, such as peptic ulcer with life-threatening complications of bleeding and perforation. But these drugs can elicit detrimental effects also in the lower digestive tract, including the occurrence of small bowel mucosal injury. A large body of experimental evidence suggests that NSAID-induced enteropathy results from direct effects, characterized by the accumulation of usually acidic NSAIDs into mucosal cells via damage to the membrane brush border and disruption of mitochondrial oxidative phosphorylation, with consequent adenosine triphosphate deficiency. These events would lead to increased mucosal permeability, with facilitation of tissue entry and detrimental actions of luminal factors, such as dietary macromolecules, bile acids, components of pancreatic juice, and bacteria, which activate the inflammatory cascade.

Our research investigates the mechanisms underlying the adverse effects of NSAIDs-induced enteropathy and possible pharmacological and non-pharmacological approaches for its prevention and treatment.

Our research focuses on two main areas:

• Molecular mechanisms that promote NSAIDs-induced enteropathy

We are currently investigating the mechanisms underlying the NSAIDS-induced enteropathy, especially in the elderly, with animal models of indomethacin or diclofenac-induced enteropathy developed in the elder rats, focusing on the interactions with other possible drugs that can participate to the induction of this pathology. 

• Novel therapeutical approaches

We ae currently characterizing the effects of probiotics in animal models of NSAIDS-induced enteropathy. We study the protective effects of these therapeutical approaches, with particular regard on the amelioration of small intestine injuries and local and systemic inflammatory parameters.