Lithium-induced renal toxicity in rats: protection by a novel antioxidant caffeic acid phenethyl ester.
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.
Oktem
Faruk
F
Department of Pediatric Nephrology, School of Medicine, Suleyman Demirel University, P.K. 13, 32100, Isparta, Turkey. oktemfaruk@hotmail.com
Ozguner
Fehmi
F
Sulak
Osman
O
Olgar
Seref
S
Akturk
Onur
O
Yilmaz
H Ramazan
HR
Altuntas
Irfan
I
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D002109:Caffeic Acids / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008094:Lithium / Q000097:blood / Q000633:toxicity*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D002109:Caffeic Acids; D008315:Malondialdehyde; D008094:Lithium; D003404:Creatinine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000118:Acetylglucosaminidase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol