Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA124

Poster Communications

Melatonin in combination with antibiotherapy alleviates gastric oxidative injury in rats: role of microbiota

A. Yildirim1, S. Arabaci Tamer1, E. Kuntsal Dertsiz2, O. Cevik3, M. Yüksel4, S. SIRVANCI2, B. Yegen1

1. Faculty of Medicine, Department of Physiology, Marmara University, Istanbul, Turkey. 2. Faculty of Medicine, Department of Histology and Embryology, Marmara University, Istanbul, Turkey. 3. Faculty of Medicine, Department of Biochemistry, Adnan Menderes University, Aydin, Turkey. 4. Vocational School of Health Related Professions, Marmara University, Istanbul, Turkey.

Gastric dysbiosis, by affecting the host inflammatory response, was suggested to have a critical role in gastric pathogenesis 1. The pineal hormone melatonin is the modulator of circadian rhythm of both the host and gut bacteria2, and exerts protective effects on acute gastric damage3. The present study was aimed to elucidate the contribution of gut dysbiosis and the effect of melatonin on the host's oxidative response to gastric ulcerogenesis. Following the ethical approval, Wistar albino rats of both sexes were randomized to control or ulcer groups. Under ketamine and chlorpromazine (100 and 10 mg/kg, intraperitoneally) anaesthesia, saline (control; n=6) or acetic acid (0.5 ml, 80 %) was applied on gastric serosa (ulcer; n=24). Before the induction of ulcer, rats were given either normal water, a cocktail of broad-spectrum antibiotics (neomycin+ampicillin+metronidazole;1g/L each), melatonin ( 40 mg/L), or melatonin plus antibiotics combination in their drinking water for 12 days. All treatments were continued on the postsurgical 3 days until they were decapitated. In gastric tissue samples, myeloperoxidase (MPO) and caspase-3 activities, and the levels of glutathione, malondialdehyde, luminol- and lucigenin-enhanced chemiluminescence (CL), 8-hydroxy-2′-deoxyguanosine (8OHDG) were measured. Gastric tissues were stained with hematoxylin and eosin for microscopical analysis, and apoptosis was evaluated by terminal deoxynucleotidly transferase dUTP nick end labeling (TUNEL) method. Statistical analysis was made using ANOVA test. Compared to control group, malondialdehyde, luminol- and lucigenin-CL, 8OHdG levels and MPO and caspase-3 activities were increased in the gastric tissues of non-treated ulcer group (p<0.01-0.001), while the antioxidant glutathione was depleted (p<0.01). The number of TUNEL-positive cells in the ulcer group was increased with respect to the control group (p<0.05). Pretreatments with antibiotics, melatonin or combination similarly reduced ulcer-induced elevations in malondialdehyde, CL, 8OHdG (p<0.001), while increased caspase-3 and MPO activities were depressed significantly only by the combination (p<0.05 and p<0.001). Ulcer-induced reduction in glutathione was replenished by both melatonin and combined therapies (p<0.05-0.01). Compared to the untreated ulcer group, less necrotic lesions and a relatively lower number of TUNEL-positive cells were observed in melatonin-, antibiotics- and melatonin+antibiotics-treated ulcer groups. The results show that antibiotics in combination with melatonin provide protection against oxidative gastric injury. Antibiotics and melatonin could be alleviating oxidative gastric injury by preventing bacterial colonization and supporting the gut microbiota in reconstructing its homeostatic state.

Where applicable, experiments conform with Society ethical requirements