title: Cardiovascular effects of low versus high-dose beta-carotene in a rat model.
abstract: β-carotene (BC), a lipid-soluble tetraterpene precursor to vitamin A, widely distributed in plants, including many used in human diet, has well-known health-enhancing properties, including reducing risk of and treatment for certain diseases. Nevertheless, BC may also act to promote disease through the activity of BC derivatives that form in the presence of external toxicants such as cigarette smoke and endogenously-produced reactive oxygen species. The present investigation evaluates the dose-dependent cardioprotective and possibly harmful properties of BC in a rat model. Adult male rats were gavage-fed BC for 4 weeks, at dosages of either 0, 30 or 150 mg/kg/day. Then, hearts excised from the animals were mounted in a "working heart" apparatus and subjected to 30 min of global ischemia, followed by 120 min of reperfusion. A panel of cardiac functional evaluations was conducted on each heart. Infarct size and total antioxidant capacity of the myocardium were assessed. Heart tissue content of heme oxygenase-1 (HO-1) by Western blot analysis; and potential direct cytotoxic effects of BC by MTT assay were evaluated. Hearts taken from rats receiving 30 mg/kg/day BC exhibited significantly improved heart function at lower reperfusion times, but lost this protection at higher BC dosage and longer reperfusion times. Myocardial HO-1 content was significantly elevated dose-responsively to both BC dosage. Finally, in vitro evaluation of BC on H9c2 cells showed that the agent significantly improved vitality of these cells in a dose range of 2.5-10 μM. Although data presented here do not allow for a comprehensive mechanistic explanation for reduced cardioprotection at high dose BC, it is speculated that since Fe2+ produced as a metabolite of HO-1 activity, may determine whether BC acts as an antioxidant or prooxidant agent, the strong induction of this enzyme in response to ischemia/reperfusion-induced oxidative stress may account for the high-dose BC loss of cardioprotection.
authors.affiliation: University of Debrecen, Faculty of Pharmacy, Department of Pharmacology, Debrecen, Hungary.
authors.forename: Evelin
authors.initials: E
authors.lastname: Csepanyi
authors.affiliation: University of Debrecen, Faculty of Pharmacy, Department of Pharmacology, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Czompa
authors.affiliation: University of Debrecen, Faculty of Pharmacy, Department of Pharmacology, Debrecen, Hungary.
authors.forename: David
authors.initials: D
authors.lastname: Haines
authors.affiliation: University of Debrecen, Faculty of Pharmacy, Department of Pharmacology, Debrecen, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Lekli
authors.affiliation: University of Debrecen, Faculty of Medicine, Department of Medical Chemistry, Debrecen, Hungary.
authors.forename: Edina
authors.initials: E
authors.lastname: Bakondi
authors.affiliation: Hemostasis, Thrombosis and Vascular Biology Research Group, Hungarian of Academy of Sciences, Debrecen, Hungary.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Balla
authors.affiliation: University of Debrecen, Faculty of Pharmacy, Department of Pharmacology, Debrecen, Hungary.
authors.forename: Arpad
authors.initials: A
authors.lastname: Tosaki
authors.affiliation: University of Debrecen, Faculty of Pharmacy, Department of Pharmacology, Debrecen, Hungary. Electronic address: bak.istvan@pharm.unideb.hu.
authors.forename: Istvan
authors.initials: I
authors.lastname: Bak
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D019207:beta Carotene / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D002316:Cardiotonic Agents; D019207:beta Carotene; D051547:Heme Oxygenase-1
keywords: Beta-carotene; CID: 5280489; Heart; Heme-oxygenase-1; Ischemia/reperfusion