Related Experiment Video
Updated: May 7, 2026

Experimental Protocol for Detecting Mitochondrial Function in Hepatocytes Exposed to Organochlorine Pesticides
Published on: September 16, 2020
Protective effect of metronidazole on uncoupling mitochondrial oxidative phosphorylation induced by NSAID: a new
A Z Leite1, A M Sipahi, A O Damião
1Department of Gastroenterology, University of São Paulo (USP) Medica1 School, São Paulo, Brazil. azl@po.cwru.edu
Background:
The pathogenesis of non-steroidal anti-inflammatory drug (NSAID) enteropathy is complex. It involves uncoupling of mitochondrial oxidative phosphorylation which alters the intercellular junction and increases intestinal permeability with consequent intestinal damage. Metronidazole diminishes the inflammation induced by indomethacin but the mechanisms remain speculative. A direct effect on luminal bacteria has traditionally been thought to account for the protective effect of metronidazole. However, a protective effect of metronidazole on mitochondrial oxidative phosphorylation has never been tested.
Aims:
To assess the protective effect of metronidazole on mitochondrial uncoupling induced by indomethacin and also on the increased intestinal permeability and macroscopic damage.
Material And Methods:
The protective effect of metronidazole was evaluated in rats given indomethacin; a macroscopic score was devised to quantify intestinal lesions, and intestinal permeability was measured by means of (51)Cr-ethylenediaminetetraacetic acid. The protective effect of metronidazole against mitochondrial uncoupling induced by indomethacin was assessed using isolated coupled rat liver mitochondria obtained from rats pretreated with metronidazole or saline.
Results:
Metronidazole significantly reduced the macroscopic intestinal damage and increase in intestinal permeability induced by indomethacin; furthermore, at the mitochondrial level, it significantly reduced the increase in oxygen consumption in state 4 induced by indomethacin and caused less reduction of the respiratory control rate.
Conclusion:
Our study confirmed the beneficial effects of metronidazole on intestinal damage and intestinal permeability, and demonstrated, for the first time, a direct protective effect of metronidazole on uncoupling of mitochondrial oxidative phosphorylation caused by NSAIDs.
Related Concept Videos
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
Drugs for Peptic Ulcer Disease: Prostaglandin Analogs as Mucosal Protective Agents
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...
Drugs for Treatment of Ulcerative Colitis in IBD
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Drug toxicity: Drug–Drug Interaction
Peptic Ulcer Disease II: Pathophysiology

