title: Effects of long-term mildronate treatment on cardiac and liver functions in rats.
abstract: Mildronate is a cardioprotective drug that improves cardiac function during ischaemia and functions by lowering l-carnitine concentration in body tissues and modulating myocardial energy metabolism. The aim of the present study was to characterise cardiovascular function and liver condition after long-term mildronate treatment in rats. In addition, changes in the plasma lipid profile, along with changes in the concentration of mildronate, l-carnitine and gamma-butyrobetaine were monitored in the rat tissues. Wistar rats were perorally treated daily with a mildronate dose of either 100, 200 or 400 mg/kg for 4, 8 or 12 weeks. The l-carnitine-lowering effect of mildronate was dose-dependent. However, the carnitine levels reached a plateau after about four weeks of treatment. During the additional weeks of treatment, the carnitine levels were not considerably changed. The obtained results provide evidence that even a high dose of mildronate does not alter cardiovascular parameters and the function of isolated rat hearts. Furthermore, the histological evaluation of liver tissue cryosections and measurement of biochemical markers of hepatic toxicity showed that all the measured values were within the normal reference range. Our results provide evidence that long-term mildronate administration induces significant changes in carnitine homeostasis, but it is not associated with cardiac impairment or disturbances in liver function.
authors: Latvian Institute of Organic Synthesis, Riga, Latvia.
authors: Edgars
authors: E
authors: Liepinsh
authors: Janis
authors: J
authors: Kuka
authors: Baiba
authors: B
authors: Svalbe
authors: Reinis
authors: R
authors: Vilskersts
authors: Elina
authors: E
authors: Skapare
authors: Helena
authors: H
authors: Cirule
authors: Osvalds
authors: O
authors: Pugovics
authors: Ivars
authors: I
authors: Kalvinsh
authors: Maija
authors: M
authors: Dambrova
mesh_terms: D000818:Animals; D001622:Betaine / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D002331:Carnitine / Q000032:analysis / Q000097:blood; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000032:analysis; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D008055:Lipids / Q000032:analysis / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D008112:Liver Glycogen / Q000032:analysis; D008297:Male; D008763:Methylhydrazines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D036401:Toxicity Tests, Chronic
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002317:Cardiovascular Agents; D008055:Lipids; D008112:Liver Glycogen; D008763:Methylhydrazines; D001622:Betaine; C002889:gamma-butyrobetaine; C050147:3-(2,2,2-trimethylhydrazine)propionate; D002334:Carnitine O-Palmitoyltransferase; D005947:Glucose; D002331:Carnitine