An in vivo, ex vivo and in vitro comparative study of activity of copper oligopeptide complexes vs Cu(II) ions.
The tetrapeptide-Cu(II) complex H-(l-His-Gly)2-OH/Cu(II), indicated as L-Cu(II), has been investigated, as compared to the Cu(II) inorganic salt CuSO4, for its antioxidative and anti-inflammatory properties under a panel of experimental conditions. Both inorganic and organic Cu(II) compounds showed comparable activities in vitro and ex vivo by: (i) protecting, in a dose-dependent manner, rat brain homogenates from Fe(III)/ascorbate- or haemoglobin-induced lipid peroxidation; (ii) inhibiting the superoxide-mediated ferricytochrome c reduction by activated macrophages. CuSO4 and L-Cu(II) also exhibited similar anti-inflammatory effects in vivo by reducing significantly the extent of carrageenan-induced edema in the rat paw. The activities of the two compounds diverged strikingly only in the xanthine/xanthine oxidase system at low phosphate buffer concentration. L-Cu(II) decreased the rate of NBT reduction by superoxide in a true SOD-like fashion without affecting urate production. Instead, Cu(II) ions caused the rapid xanthine oxidase inactivation thus inhibiting both urate and superoxide production; this effect might be ascribed to the superoxide-mediated generation of the strong oxidant Cu(III) and its interaction with the enzyme. The administration of Cu(II), whether complexed with linear oligopeptides or as an inorganic salt, to animals or tissue extracts, conferred protection against oxidation and ought, conceivably, to interact with endogenous biological molecules and form highly bioavailable complexes which serve, subsequently, as the real scavengers. Moreover, the claimed prominent scavenger activities of Cu(II)-oligopeptide complexes over inorganic copper ions could be realised only in very simple in vitro systems through mechanisms which, although of biochemical interest, are unlikely to be of physiopathological significance.
Dipartimento di Farmacologia Preclinica e Clinica, Firenze, Italy.
M
M
Ciuffi
C
C
Cellai
S
S
Franchi-Micheli
L
L
Zilletti
M
M
Ginanneschi
M
M
Chelli
A M
AM
Papini
F
F
Paoletti
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology; D002351:Carrageenan; D002413:Cations, Divalent / Q000494:pharmacology; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D003300:Copper / Q000494:pharmacology*; D003574:Cytochrome c Group / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005528:Foot / Q000473:pathology; D016166:Free Radical Scavengers / Q000378:metabolism; D006168:Guinea Pigs; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002413:Cations, Divalent; D003574:Cytochrome c Group; D016166:Free Radical Scavengers; D008054:Lipid Peroxides; D009842:Oligopeptides; D009942:Organometallic Compounds; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003300:Copper; D002351:Carrageenan; D013482:Superoxide Dismutase