title: Mitochondrial dysfunction in an animal model of hyperoxaluria: a prophylactic approach with fucoidan.
abstract: Oxalate/calcium oxalate toxicity is mediated through generation of reactive oxygen species in a process that partly depends upon events that induce mitochondrial damage. Mitochondrial dysfunction is an important event favoring stone formation. The objective of the present study was to investigate whether mitochondria is a target for oxalate/calcium oxalate and the plausible role of naturally occurring glycosaminoglycans from edible seaweed, fucoidan in ameliorating mitochondrial damage. Male albino rats of Wistar strain were divided into four groups and treated as follows: Group I: vehicle treated control, Group II: hyperoxaluria was induced with 0.75% ethylene glycol in drinking water for 28 days, Group III: fucoidan from F. vesiculosus (5 mg/kg b.wt, s.c) from the 8th day of the experimental period, Group IV: ethylene glycol+fucoidan treated rats. The tricarboxylic acid (TCA) cycle enzymes like succinate dehydrogenase, isocitrate dehydrogenase, malate dehydrogenase and respiratory complex enzyme activities were assessed to evaluate mitochondrial function. Oxidative stress was assessed based on the activities of antioxidant enzymes, level of reactive oxygen species, lipid peroxidation and reduced glutathione. Mitochondrial swelling was also analyzed. Ultra structural changes in renal tissue were analyzed with electron microscope. Hyperoxaluria induced a decrease in the activities of TCA cycle enzymes and respiratory complex enzymes. The oxidative stress was evident by the decrease in antioxidant enzymes, glutathione and an increase in reactive species and lipid peroxidation in mitochondria. Mitochondrial damage was evident by increased mitochondrial swelling. Administration of fucoidan, decreased reactive oxygen species, lipid peroxidation (P<0.05), mitochondrial swelling and increased the activities of antioxidant enzymes and glutathione levels (P<0.05) and normalized the activities of mitochondrial TCA cycle and respiratory complex enzymes (P<0.05). From the present study, it can be concluded that mitochondrial damage is an essential event in hyperoxaluria, and fucoidan was able to effectively prevent it and thereby the renal damage in hyperoxaluria.
authors.affiliation: Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai - 600 113, India.
authors.forename: Coothan Kandaswamy
authors.initials: CK
authors.lastname: Veena
authors.forename: Anthony
authors.initials: A
authors.lastname: Josephine
authors.forename: Sreenivasan P
authors.initials: SP
authors.lastname: Preetha
authors.forename: Nachiappa Ganesh
authors.initials: NG
authors.lastname: Rajesh
authors.forename: Palaninathan
authors.initials: P
authors.lastname: Varalakshmi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D002952:Citric Acid Cycle / Q000187:drug effects; D004195:Disease Models, Animal; D019855:Ethylene Glycol / Q000633:toxicity; D044645:Fucus / Q000737:chemistry*; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006959:Hyperoxaluria / Q000139:chemically induced / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D011134:Polysaccharides; D017382:Reactive Oxygen Species; C007789:fucoidan; D019855:Ethylene Glycol; D005978:Glutathione