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Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: l-NAME, l-arginine, stable gastric pentadecapeptide BPC 157

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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.

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Acknowledgements

This research was supported from Ministry of Science, Education and Sports, Republic of Croatia (Grant Number 108-1083570-3635).

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Authors and Affiliations

  1. Departments of Pharmacology and Pathology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia

    Krešimir Luetic, Mario Sucic, Josipa Vlainic, Zeljka Belosic Halle, Dean Strinic, Tinka Vidovic, Franka Luetic, Marinko Marusic, Sasa Gulic, Tatjana Turudic Pavelic, Antonio Kokot, Ranka Serventi Seiwerth, Domagoj Drmic, Lovorka Batelja, Sven Seiwerth & Predrag Sikiric

  2. Faculty of Medicine, J.J. Strossmayer University of Osijek, J. Huttlera 4, 31000, Osijek, Croatia

    Krešimir Luetic, Mario Sucic, Zeljka Belosic Halle, Dean Strinic, Marinko Marusic & Antonio Kokot

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  1. Krešimir Luetic
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  2. Mario Sucic
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Correspondence to Predrag Sikiric.

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Luetic, K., Sucic, M., Vlainic, J. et al. Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: l-NAME, l-arginine, stable gastric pentadecapeptide BPC 157. Inflammopharmacol 25, 255–264 (2017). https://doi.org/10.1007/s10787-017-0330-7

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