Intestinal motility disorder induced by peroxides: possible role of lipid peroxidation.
The effect of oxidative stress on the rat small intestine was investigated by pretreatment of isolated segments from the jejunum with hydrogen peroxide or cumene hydroperoxide. Both peroxides induced responses in the small intestine, viz. a contraction followed by a slow relaxation. The contraction could be blocked by the cyclooxygenase inhibitor indomethacin and the phospholipase A2 inhibitor quinacrine, suggesting a role for prostaglandins in the response. Pretreatment of intestinal segments with the peroxides diminished the muscarinic cholinergic response to methacholine. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) and the antioxidant butylated hydroxytoluene (BHT) both protected against the damage induced by cumene hydroperoxide, but did not influence the effect of hydrogen peroxide on the muscarinic response. In contrast to hydrogen peroxide, cumene hydroperoxide induced lipid peroxidation in intestinal membranes, which could also be blocked by NDGA or BHT. We conclude that cumene hydroperoxide alters the muscarinic response in the rat jejunum by the induction of lipid peroxidation, whereas the damage by hydrogen peroxide is probably induced intracellularly.
Van der Vliet
A
A
Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Tuinstra
T J
TJ
Rademaker
B
B
Bast
A
A
D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006162:Guanylate Cyclase / Q000502:physiology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D006878:Hydroxides; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D015227:Lipid Peroxidation; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects
D001555:Benzene Derivatives; D006878:Hydroxides; D011976:Receptors, Muscarinic; D017665:Hydroxyl Radical; D009637:Masoprocol; D006861:Hydrogen Peroxide; D010741:Phospholipases A; D054467:Phospholipases A2; D006162:Guanylate Cyclase; C007164:cumene hydroperoxide; D007213:Indomethacin