Turan Tunc1, Vural Kesik1, Hilmi Demirin2, Nail Ersoz3, Sebahattin Vurucu1, Mustafa Kul4, Bülent Uysal5, Serdar Sadir5, Ahmet Guven6, Emin Oztas7. 1. Department of Pediatrics, Gülhane Military Medical Academy, Ankara, Turkey. 2. Department of Biochemistry, Gülhane Military Medical Academy, Ankara, Turkey. 3. Department of General Surgery, Gülhane Military Medical Academy, Ankara, Turkey. 4. Department of Pediatrics, Gülhane Military Medical Academy, Haydarpasa, Turkey. 5. Department of Physiology, Gülhane Military Medical Academy, Ankara, Turkey. 6. Department of Pediatric Surgery, Gülhane Military Medical Academy, Ankara, Turkey. 7. Department of Histology and Embryology, Gülhane Military Medical Academy, Ankara, Turkey.
Abstract
BACKGROUND: The reactive oxygen and nitrogen species generated during reperfusion of tissue are characteristic of intestinal ischemia and reperfusion (IIR) injury. OBJECTIVE: This study was designed to assess whether the administration of aminoguanidine (AG), a selective nitric oxide synthase inhibitor, and/or melatonin has protective potential in IIR injury. METHODS: Male Wistar albino rats (age, 3-4 weeks; weight, 100-150 g) were divided in a nonrandom fashion into 5 groups of equal size: group 1, IIR injury + AG 100 mg/kg; group 2, IIR injury + melatonin 10 mg/kg; group 3, IIR injury + AG 100 mg/kg + melatonin 10 mg/kg; group 4, sham operation; and group 5, IIR injury alone. Sixty minutes of intestinal ischemia and 4 hours of reperfusion were carried out in all but the sham-operation group. Ileal specimens were obtained from all rats to determine the extent of histologic changes, measure tissue concentrations of malondialdehyde (MDA) and protein carbonyl (PC), and assess the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Specimens were also assessed and scored by a pathologist blinded to the experiment and the data. RESULTS: Forty rats were divided into 5 groups of 8 each; all 40 survived until study end. In the IIR injury-alone group, mean (SD) MDA concentration and PC content were significantly higher than that of the sham-operation group, and SOD and GPx activity were significantly lower: MDA concentration, 0.86 (0.03) versus 0.54 (0.01) mmol/g protein, respectively; PC content, 0.60 (0.02) versus 0.34 (0.01) mmol/g protein; SOD activity, 104.33 (43.14) versus 2954.72 (109.55) U/g protein; and GPx activity, 10.44 (0.63) versus 24.34 (1.77) U/g protein (all, P < 0.001). Administration of AG, melatonin, and the AG/melatonin combination was associated with significantly higher SOD (1802.31 [102.35], 1776.50 [58.41], and 1924.28 [98.10] U/g protein, respectively) and GPx (17.36 [1.23], 15.96 [1.08], and 18.06 [1.72] U/g protein) activity and significantly lower MDA concentration (0.62 [0.02], 0.64 [0.02], and 0.56 [0.01] mmol/g protein) and PC content (0.53 [0.03], 0.51 [0.01], and 0.49 [0.02] mmol/g protein) compared with the IIR injury-alone group (P < 0.001). Mean intestinal mucosal injury scores were significantly lower in the 3 treatment groups (2.12 [0.35], 1.75 [0.46], and 1.12 [0.35]) compared with the IIR injury-alone group (3.87 [0.35]; all, P < 0.001). CONCLUSION: In this study, AG, melatonin, or both administered in combination were associated with improvements in oxidative markers in this rat model of IIR injury.
BACKGROUND: The reactive oxygen and nitrogen species generated during reperfusion of tissue are characteristic of intestinal ischemia and reperfusion (IIR) injury. OBJECTIVE: This study was designed to assess whether the administration of aminoguanidine (AG), a selective nitric oxide synthase inhibitor, and/or melatonin has protective potential in IIR injury. METHODS: Male Wistar albino rats (age, 3-4 weeks; weight, 100-150 g) were divided in a nonrandom fashion into 5 groups of equal size: group 1, IIR injury + AG 100 mg/kg; group 2, IIR injury + melatonin 10 mg/kg; group 3, IIR injury + AG 100 mg/kg + melatonin 10 mg/kg; group 4, sham operation; and group 5, IIR injury alone. Sixty minutes of intestinal ischemia and 4 hours of reperfusion were carried out in all but the sham-operation group. Ileal specimens were obtained from all rats to determine the extent of histologic changes, measure tissue concentrations of malondialdehyde (MDA) and protein carbonyl (PC), and assess the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Specimens were also assessed and scored by a pathologist blinded to the experiment and the data. RESULTS: Forty rats were divided into 5 groups of 8 each; all 40 survived until study end. In the IIR injury-alone group, mean (SD) MDA concentration and PC content were significantly higher than that of the sham-operation group, and SOD and GPx activity were significantly lower: MDA concentration, 0.86 (0.03) versus 0.54 (0.01) mmol/g protein, respectively; PC content, 0.60 (0.02) versus 0.34 (0.01) mmol/g protein; SOD activity, 104.33 (43.14) versus 2954.72 (109.55) U/g protein; and GPx activity, 10.44 (0.63) versus 24.34 (1.77) U/g protein (all, P < 0.001). Administration of AG, melatonin, and the AG/melatonin combination was associated with significantly higher SOD (1802.31 [102.35], 1776.50 [58.41], and 1924.28 [98.10] U/g protein, respectively) and GPx (17.36 [1.23], 15.96 [1.08], and 18.06 [1.72] U/g protein) activity and significantly lower MDA concentration (0.62 [0.02], 0.64 [0.02], and 0.56 [0.01] mmol/g protein) and PC content (0.53 [0.03], 0.51 [0.01], and 0.49 [0.02] mmol/g protein) compared with the IIR injury-alone group (P < 0.001). Mean intestinal mucosal injury scores were significantly lower in the 3 treatment groups (2.12 [0.35], 1.75 [0.46], and 1.12 [0.35]) compared with the IIR injury-alone group (3.87 [0.35]; all, P < 0.001). CONCLUSION: In this study, AG, melatonin, or both administered in combination were associated with improvements in oxidative markers in this rat model of IIR injury.
Authors: U Koltuksuz; S Ozen; E Uz; M Aydinç; A Karaman; A Gültek; O Akyol; M H Gürsoy; E Aydin Journal: J Pediatr Surg Date: 1999-10 Impact factor: 2.545
Authors: C Hammerman; D Goldschmidt; M S Caplan; M Kaplan; M S Schimmel; A I Eidelman; D Branski; A Hochman Journal: J Pediatr Gastroenterol Nutr Date: 1999-07 Impact factor: 2.839