title: Ligustrazine attenuates elevated levels of indoxyl sulfate, kidney injury molecule-1 and clusterin in rats exposed to cadmium.
abstract: In this study, we aimed at evaluating the effect of ligustrazine, a major constituent of Ligusticum wallichii from traditional Chinese medicine, on Cd-induced changes in nephrotoxicity indices. Rats were divided into four experimental groups: control; ligustrazine; Cd and ligustrazine+Cd. Cd treated alone group showed significant decreases (P<0.05) in body weight, renal levels of superoxide dismutase (SOD) and glutathione reductase (GR); and significant increases (P<0.05) in urine volume (24h), pH values, serum blood urea nitrogen (BUN), serum uric acid, kidney malondialdehyde (MDA), urinary total protein, urinary glucose, urinary lactate dehydrogenase (LDH) and urinary alkaline phosphatase (ALP). Apart from indoxyl sulfate (a uremic toxin), two newly accepted nephrotoxicity biomarkers including kidney injury molecule-1 (kim-1) and clusterin were also found to be increased. Nonetheless, all these effects induced by Cd were reversed upon treatment by ligustrazine although it failed in decreasing the concentrations of Cd in kidney and urine. Histopathological studies in Cd-treated rats exhibited renal tubule damage, which was also ameliorated by ligustrazine pretreatment. These results suggest that ligustrazine exhibits protective effects on Cd-induced nephrotoxicity. Additionally, this study also demonstrates Cd exposure induces elevated levels of indoxyl sulfate in serum and kidney, and clusterin in urine.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Lan
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
authors.forename: Kai Shun
authors.initials: KS
authors.lastname: Bi
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China. Electronic address: cebu007@126.com.
authors.forename: Xiao Hui
authors.initials: XH
authors.lastname: Chen
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002104:Cadmium / Q000032:analysis / Q000633:toxicity* / Q000652:urine; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000652:urine; D051152:Clusterin / Q000378:metabolism* / Q000652:urine; D007200:Indican / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D002104:Cadmium; D015815:Cell Adhesion Molecules; D051152:Clusterin; D007200:Indican; D011719:Pyrazines; D013482:Superoxide Dismutase; C498500:Clu protein, rat; C110936:Havcr1 protein, rat; C017953:tetramethylpyrazine
keywords: Antioxidants; Biomarkers; Cadmium; Indoxyl sulfate; Ligustrazine