Mito dysfunction in hyperoxaluria and protection by fucoidan

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Eur J Pharmacol. 2008 Jan 28;579(1-3):330-6. Epub 2007 Oct 16.

Mitochondrial dysfunction in an animal model of hyperoxaluria: a

prophylactic approach with fucoidan.

Veena CK, phine A, Preetha SP, Rajesh NG, Varalakshmi P.

Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of

Basic Medical Sciences, University of Madras, Taramani Campus, Chennai - 600

113, India.

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. PMID: 18001705 [