title: Involvement of oxidative stress in the mechanism of triptolide-induced acute nephrotoxicity in rats.
abstract: Triptolide is one of the most widely used and one of the most potent Chinese traditional herbal medicines. However, side effects, especially nephrotoxicity, limit the use of triptolide. It has been reported that oxidative stress is involved in drug-induced nephrotoxicity. In the present study, we focused on observing triptolide-induced acute nephrotoxicity in rats and investigating whether or not oxidative stress is involved in the pathogenesis of this process. The results showed that a single large dose peritoneal injection of triptolide caused severe oxidative stress characterized by significant decreases of renal SOD and GSH-Px activities, as well as significant increase of renal MDA content and also led to severe impairment of renal structure and function characterized by injury of renal tubules observed in HE-stained and TUNEL-stained slides and increases of Cre and BUN concentrations in a short time. However, pretreatment with the antioxidant vitamin C significantly ameliorated triptolide-induced depletion in renal SOD and GSH-Px activities, caused marked normalization of renal MDA content and also blunt the impairment of renal tubules and renal function. These results suggest that triptolide induces oxidative stress via impairing the antioxidant system, and oxidative stress contributes, at least in part, to the mechanism of triptolide-induced acute nephrotoxicity.
authors.affiliation: Faculty of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, Hubei, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Liang
authors.initials: L
authors.lastname: Ren
authors.forename: Luo
authors.initials: L
authors.lastname: Zhuo
authors.forename: Sunnassee
authors.initials: S
authors.lastname: Ananda
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004224:Diterpenes / Q000302:isolation & purification / Q000633:toxicity*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000633:toxicity*; D004852:Epoxy Compounds / Q000302:isolation & purification / Q000633:toxicity; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010616:Phenanthrenes / Q000302:isolation & purification / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide