title: Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: L-NAME, L-arginine, stable gastric pentadecapeptide BPC 157.
abstract: We revealed a new point with cyclophosphamide (150 mg/kg/day intraperitoneally for 7 days): we counteracted both rat stomach and duodenal ulcers and increased NO- and MDA-levels in these tissues. As a NO-system effect, BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once a day or in drinking water, till the sacrifice) attenuated the increased NO- and MDA-levels and nullified, in rats, severe cyclophosphamide-ulcers and even stronger stomach and duodenal lesions after cyclophosphamide + L-NAME (5 mg/kg intraperitoneally once a day). L-arginine (100 mg/kg intraperitoneally once a day not effective alone) led L-NAME-values only to the control values (cyclophosphamide + L-NAME + L-arginine-rats). Briefly, rats were sacrificed at 24 h after last administration on days 1, 2, 3, or 7, and assessment included sum of longest lesions diameters (mm) in the stomach and duodenum, oxidative stress by quantifying thiobarbituric acid reactivity as malondialdehyde equivalents (MDA), NO in stomach and duodenal tissue samples using the Griess reaction. All these parameters were highly exaggerated in rats who underwent cyclophosphamide treatment. We identified high MDA-tissue values, high NO-tissue values, ulcerogenic and beneficial potential in cyclophosphamide-L-NAME-L-arginine-BPC 157 relationships. This suggests that in cyclophosphamide damaged rats, NO excessive release generated by the inducible isozyme, damages the vascular wall and other tissue cells, especially in combination with reactive oxygen intermediates, while failing endothelial production and resulting in further aggravation by L-NAME which was inhibited by L-arginine. Finally, BPC 157, due to its special relations with NO-system, may both lessen increased MDA- and NO-tissues values and counteract effects of both cyclophosphamide and L-NAME on stomach and duodenal lesions.
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.|Faculty of Medicine, J.J. Strossmayer University of Osijek, J. Huttlera 4, 31000, Osijek, Croatia.
authors.forename: Krešimir
authors.initials: K
authors.lastname: Luetic
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.|Faculty of Medicine, J.J. Strossmayer University of Osijek, J. Huttlera 4, 31000, Osijek, Croatia.
authors.forename: Mario
authors.initials: M
authors.lastname: Sucic
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Josipa
authors.initials: J
authors.lastname: Vlainic
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.|Faculty of Medicine, J.J. Strossmayer University of Osijek, J. Huttlera 4, 31000, Osijek, Croatia.
authors.forename: Zeljka Belosic
authors.initials: ZB
authors.lastname: Halle
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.|Faculty of Medicine, J.J. Strossmayer University of Osijek, J. Huttlera 4, 31000, Osijek, Croatia.
authors.forename: Dean
authors.initials: D
authors.lastname: Strinic
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Tinka
authors.initials: T
authors.lastname: Vidovic
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Franka
authors.initials: F
authors.lastname: Luetic
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.|Faculty of Medicine, J.J. Strossmayer University of Osijek, J. Huttlera 4, 31000, Osijek, Croatia.
authors.forename: Marinko
authors.initials: M
authors.lastname: Marusic
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Sasa
authors.initials: S
authors.lastname: Gulic
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Tatjana Turudic
authors.initials: TT
authors.lastname: Pavelic
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.|Faculty of Medicine, J.J. Strossmayer University of Osijek, J. Huttlera 4, 31000, Osijek, Croatia.
authors.forename: Antonio
authors.initials: A
authors.lastname: Kokot
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Ranka Serventi
authors.initials: RS
authors.lastname: Seiwerth
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Domagoj
authors.initials: D
authors.lastname: Drmic
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Lovorka
authors.initials: L
authors.lastname: Batelja
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Sven
authors.initials: S
authors.lastname: Seiwerth
authors.affiliation: Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia. sikiric@mef.hr.
authors.forename: Predrag
authors.initials: P
authors.lastname: Sikiric
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage; D001120:Arginine / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000633:toxicity*; D004359:Drug Therapy, Combination; D005260:Female; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010437:Peptic Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage*; D011506:Proteins / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000897:Anti-Ulcer Agents; D010446:Peptide Fragments; D011506:Proteins; D009569:Nitric Oxide; C083833:BPC 157; D003520:Cyclophosphamide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester
keywords: BPC 157; Cyclophosphamide; Duodenal lesions; Gastric lesions; NO-MDA-tissue levels; NO-system; Rats