Doxorubicine-congestive heart failure-increased big endothelin-1 plasma concentration: reversal by amlodipine, losartan, and gastric pentadecapeptide BPC157 in rat and mouse.
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 microg, 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 microg/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.
Lovric-Bencic
Martina
M
Department of Pharmacology, Medical Faculty, University of Zagreb, Croatia.
Sikiric
Predrag
P
Hanzevacki
Jadranka S
JS
Seiwerth
Sven
S
Rogic
Dunja
D
Kusec
Vesna
V
Aralica
Gorana
G
Konjevoda
Pasko
P
Batelja
Lovorka
L
Blagaic
Alenka B
AB
D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004317:Doxorubicin / Q000633:toxicity; D019332:Endothelin-1 / Q000097:blood*; D005753:Gastric Mucosa / Q000378:metabolism; D006333:Heart Failure / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D011506:Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects
D019332:Endothelin-1; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D017311:Amlodipine; D004317:Doxorubicin; C083833:BPC 157; D019808:Losartan