Doxorubicine-Congestive Heart Failure-Increased Big Endothelin-1 Plasma Concentration: Reversal by Amlodipine, Losartan, and Gastric Pentadecapeptide BPC157 in Rat and Mouse

• Main Authors: Martina Lovric-Bencic (Author), Predrag Sikiric (Author), Jadranka S. Hanzevacki (Author), Sven Seiwerth (Author), Dunja Rogic (Author), Vesna Kusec (Author), Gorana Aralica (Author), Pasko Konjevoda (Author), Lovorka Batelja (Author), Alenka B. Blagaic (Author)
• Format: Book
• Published: Elsevier, 2004-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Overall, doxorubicine-congestive heart failure (CHF) (male Wistar rats and NMRI mice; 6 challenges with doxorubicine (2.5 mg/kg, i.p.) throughout 15 days and then a 4-week-rest period) is consistently deteriorating throughout next 14 days, if not reversed or ameliorated by therapy (/kg per day): a stable gastric pentadecapeptide BPC157 (GEPPPGKPADDAGLV, MW 1419, promisingly studied for inflammatory bowel disease (Pliva; PL 10, PLD-116, PL 14736)) (10 μg, 10 ng), losartan (0.7 mg), amlodipine (0.07 mg), given intragastrically (i.g.) (once daily, rats) or in drinking water (mice). Assessed were big endothelin-1 (BET-1) and plasma enzyme levels (CK, MBCK, LDH, AST, ALT) before and after 14 days of therapy and clinical status (hypotension, increased heart rate and respiratory rate, and ascites) every 2 days. Controls (distilled water (5 ml/kg, i.g., once daily) or drinking water (2 ml/mouse per day) given throughout 14 days) exhibited additionally increased BET-1 and aggravated clinical status, while enzyme values maintained their initial increase. BPC157 (10 μg/kg) and amlodipine treatment reversed the increased BET-1 (rats, mice), AST, ALT, CK (rats, mice), and LDH (mice) values. BPC157 (10 ng/kg) and losartan opposed further increase of BET-1 (rats, mice). Losartan reduces AST, ALT, CK, and LDH serum values. BPC157 (10 ng/kg) reduces AST and ALT serum values. Clinical status of CHF-rats and -mice is accordingly improved by the BPC157 regimens and amlodipine. Keywords:: pentadecapeptide BPC157, big endothelin-1, doxorubicine-congestive heart failure, amlodipine, losartan

Item Description

1347-8613
10.1254/jphs.95.19