Possible radical scavenging properties of cicletanine and renal protection in Dahl salt sensitive rats.
Much interest in cicletanine, a novel antihypertensive drug, has grown because it uniquely stimulates prostacyclin (PGI2) production and may, thereby, provide further cardiovascular protection. We postulated that cicletanine may be an antioxidant, and assessed its ability to protect the kidney in Dahl salt-sensitive (Dahl S) rats on a high salt diet. Cicletanine eradicated in vitro a stable radical, DPPH, and decreased the lipid peroxidation both in rat brain homogenate and in a xanthine-xanthine oxidase (X-XOD) superoxide generating system. Furthermore, cicletanine attenuated the inhibition of PGI2 synthase activity by 15HPETE. However, cicletanine did not exhibit superoxide dismutase-like activity in X-XOD system, suggesting that it behaves primarily as a hydroxy radical scavenger. A 6 week cicletanine treatment reduced blood pressure in Dahl S rats fed a high salt diet, and ameliorated functional and morphological injury to the kidney. This attenuation of glomerular sclerosis correlated with the attenuation of lipid peroxidation in the kidney homogenate. These data indicate that cicletanine is an antioxidant that protects the kidney from salt-induced hypertension in Dahl salt-sensitive strain rats.
Uehara
Y
Y
Second Department of Medicine, University of Tokyo, Japan.
Kawabata
Y
Y
Hirawa
N
N
Takada
S
S
Nagata
T
T
Numabe
A
A
Iwai
J
J
Sugimoto
T
T
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D016166:Free Radical Scavengers; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D015289:Leukotrienes / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008054:Lipid Peroxides / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
D000959:Antihypertensive Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D015289:Leukotrienes; D008054:Lipid Peroxides; D011725:Pyridines; D012982:Sodium, Dietary; D014970:Xanthines; D019820:Xanthine; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C038068:cicletanine; D011464:Epoprostenol; D014969:Xanthine Oxidase