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Attenuation of the Deleterious Course and Gastric Lesions after Bilateral Nephrectomy in Rats, NO‐system relation. BPC 157, L‐arginine, L‐NAME
Author(s) -
Drmic Domagoj,
Sucic Mario,
Sever Anita Zenko,
Kolenc Danijela,
Andrijasevic Vedran,
Suran Jelena,
Seiwerth Sven,
Sikiric Predrag
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.720.2
Subject(s) - medicine , arginine , creatinine , nephrectomy , gastroenterology , lesion , endocrinology , kidney , pathology , chemistry , biochemistry , amino acid
Aim Chronic renal insufficiency might be associated with increased peptic ulcer presentation. Recently, stable gastric pentadecapeptide BPC 157 (an antiulcer peptide tested in clinical trials, for inflammatory bowel disease and multiple sclerosis, effective against a variety of different ulcerogens), counteracted gastric lesions and other disturbances, after bilateral nephrectomy in rats. Now, we demonstrate that this effect might be NO‐system related. Materials and methods Rats were subjected to bilateral nephrectomy, sacrificed either at 24h or 48h. Medication (/kg i.p.) BPC 157 (10μg, 10ng), L‐arginine (100mg), L‐NAME (5mg) alone and/or combined, was given immediately after nephrectomy. Assessment included gastric lesions, gross clinical presentation, urea, creatinine, AST, ALT, bilirubin, K, Na, Mg, Ca, inorganic phosphate, values in serum as described (Sikiric et al, Curr Pharm Des. 2014;20(7):1126–35) as well as brain lesion presentation, as described (Sikiric et al., Curr Neuropharm. 2015, in press). Results Comparison of gastric lesions (means±SD, sum of the longest lesions diameters, mm) in the nephrectomized rats (10.5±1.5 (24h), 15.0±3.0 (48h)), revealed that the gastric lesions were either consistently attenuated (vs. *P<0.05, at least) in BPC 157‐rats (1.8±0.5 (24h), 1.0±0.5 (48h)), L‐arginine‐rats (5.8±0.8 (24h), 5.0±0.7 (48h)), BPC 157+L‐arginine‐rats (0.8±0.5 (24h), 1.3±0.4 (48h)), L‐arginine+L‐NAME‐rats (4.9±0.4 (24h), 5.3±0.5 (48h)), BPC 157+L‐NAME‐rats (1.3±0.4 (24h), 1.2±0.5 (48h)), BPC 157+L‐arginine+L‐NAME‐rats (1.6±0.4 (24h), 1.4±0.3 (48h)) or aggravated (vs. *P<0.05, at least) in L‐NAME‐rats (20.5±1.7(24h), 25.0±2.0 (48h)). The influence (decreasing/increasing) on the otherwise increased values of the urea, creatinine, AST, inorganic phosphates as well as on rat edema formation (controls rats were edematous (scored 0–3) (Min/Med/Max, scored 3/3/3)) (attenuation/aggravation) was in accordance with the influence on gastric lesions(attenutation/aggravation) while K, Na, Mg, Ca values in serum were not affected. Conclusions Applied after nephrectomy, the otherwise deleterious course was attenuated after BPC 157, and/or L‐arginine administration, while they were aggravated by L‐NAME admisitration, an effect also counteracted by BPC 157 and L‐arginine, portraying it as NO‐related. Gastric lesions seem to be a particular indicator of the severity of the course of events which ensue after nephrectomy. Support or Funding Information This research was supported by Grant 108‐1083570‐3635, Ministry of Science, Education and Sports, Republic of Croatiaand by Grant BM099, University of Zagreb, Republic of Croatia.