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Lithium-induced renal toxicity in rats: protection by a novel antioxidant caffeic acid phenethyl ester.

Abstract
Lithium carbonate used in the long-term treatment of manic-depressive illness has been reported to lead to progressive renal impairment in rats and humans. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, protects tissues from reactive oxygene species mediated oxidative stress in ischemia-reperfusion and toxic injuries. The beneficial effect CAPE on lithium-induced nephrotoxicity has not been reported yet. The purpose of this study was to examine a possible renoprotective effect of CAPE against lithium-induced nephrotoxicity in a rat model. Twenty-two adult male rats were randomly divided into three experimental groups, as follows: control group, lithium-treated group (Li), and lithium plus CAPE-treated group (Li+CAPE). Li were treated intraperitoneally (i.p.) with 25 mg/kg Li2CO3 solution in 0.9% NaCl twice daily for 4 weeks. CAPE was co-administered i.p. with a dose of 10 microM/kg/day for 4 weeks. Serum Li, blood urea nitrogen and plasma creatinine, urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury), and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of oxidative stress-induced renal impairment in Li-treated rats. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in renal tissue. Serum Li levels were found high in the Li and Li+CAPE groups. In Li-administrated rats, urinary NAG and renal MDA levels were increased according to control and Li+CAPE groups (p < 0.05). CAPE caused a significant reduction in the levels of these parameters. Likewise, renal SOD, CAT and GSH-Px activities were decreased in Li-administrated animals; CAPE caused a significant increase in the activities of these antioxidant enzymes. In conclusion, CAPE treatment has a protective effect against Li-induced renal tubular damage and oxidative stress in a rat model.
AuthorsFaruk Oktem, Fehmi Ozguner, Osman Sulak, Seref Olgar, Onur Akturk, H Ramazan Yilmaz, Irfan Altuntas
JournalMolecular and cellular biochemistry (Mol Cell Biochem) Vol. 277 Issue 1-2 Pg. 109-15 (Sep 2005) ISSN: 0300-8177 [Print] Netherlands
PMID16132721 (Publication Type: Journal Article)
Chemical References
  • Antioxidants
  • Caffeic Acids
  • Malondialdehyde
  • Lithium
  • Creatinine
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Acetylglucosaminidase
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol
Topics
  • Acetylglucosaminidase (urine)
  • Animals
  • Antioxidants (pharmacology)
  • Blood Urea Nitrogen
  • Caffeic Acids (pharmacology)
  • Catalase (metabolism)
  • Creatinine (blood)
  • Glutathione Peroxidase (metabolism)
  • Kidney (drug effects, metabolism)
  • Lithium (blood, toxicity)
  • Male
  • Malondialdehyde (metabolism)
  • Phenylethyl Alcohol (analogs & derivatives, pharmacology)
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase (metabolism)

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