title: The decreased expression of mitofusin-1 and increased fission-1 together with alterations in mitochondrial morphology in the kidney of rats with chronic fluorosis may involve elevated oxidative stress.
abstract: This study was designed to characterize changes in the expression of mitofusin-1 (Mfn1) and fission-1 (Fis1), as well as in mitochondrial morphology in the kidney of rats subjected to chronic fluorosis and to elucidate whether any mitochondrial injury observed is associated with increased oxidative stress. Sixty Sprague-Dawley (SD) rats were divided randomly into 3 groups of 20 each, i.e., the untreated control group (natural drinking water containing <0.5mg fluoride/L), the low-fluoride group (drinking water supplemented with 10mg fluoride/L, prepared with NaF) and the high-fluoride group (50mg fluoride/L), and treated for 6 months. Thereafter, renal expression of Mfn1 and Fis1 at both the protein and mRNA levels was determined by immunohistochemistry and real-time PCR, respectively. In addition, the malondiadehyde (MDA) was quantitated by the thiobarbituric acid procedure and the total antioxidative capability (T-AOC) by a colorimetric method. The morphology of renal mitochondria was observed under the transmission electron microscope. In the renal tissues of rats with chronic fluorosis, expression of both Mfn1 protein and mRNA was clearly reduced, whereas that of Fis1 was elevated. The level of MDA was increased and the T-AOC lowered. Swollen or fragmented mitochondria in renal cells were observed under the electronic microscope. These findings indicate that chronic fluorosis can lead to the abnormal mitochondrial dynamics and changed morphology in the rat kidney, which in mechanism might be induced by a high level of oxidative stress in the disease.
authors: Department of Pathology in the Affiliated Hospital, Guiyang Medical University, Guiyang 550004, PR China.
authors: Shuang-Li
authors: SL
authors: Qin
authors: Key Laboratory of Molecular Biology, Guiyang Medical University, Guiyang 550004, PR China.
authors: Jie
authors: J
authors: Deng
authors: Department of Pathology in the Affiliated Hospital, Guiyang Medical University, Guiyang 550004, PR China.
authors: Di-Dong
authors: DD
authors: Lou
authors: Key Laboratory of Molecular Biology, Guiyang Medical University, Guiyang 550004, PR China.
authors: Wen-Feng
authors: WF
authors: Yu
authors: KI-Alzheimer Disease Research Center, Novum, Karolinska Institute, SE 14186 Huddinge, Sweden.
authors: Jinjing
authors: J
authors: Pei
authors: Department of Pathology in the Affiliated Hospital, Guiyang Medical University, Guiyang 550004, PR China; Key Laboratory of Molecular Biology, Guiyang Medical University, Guiyang 550004, PR China. Electronic address: zhizhongguan@yahoo.com.
authors: Zhi-Zhong
authors: ZZ
authors: Guan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002908:Chronic Disease; D060766:Drinking Water / Q000737:chemistry; D005459:Fluorides / Q000652:urine; D009050:Fluorosis, Dental / Q000235:genetics / Q000473:pathology* / Q000652:urine; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D060766:Drinking Water; C503403:Fis1 protein, rat; D008565:Membrane Proteins; C489709:Mfn1 protein, rat; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D008315:Malondialdehyde; D005459:Fluorides
keywords: Fis1; Fluorosis; Mfn1; Oxidative stress; Rats