Effect of iron and ascorbate on cyclosporine-induced oxidative damage of kidney mitochondria and microsomes

Lee, Suk Ha; Yoon, Young Chul; Jang, Yoon Young; Song, Jin Ho; Han, Eun Sook; Lee, Chung Soo

doi:10.1006/phrs.2000.0759

Cited by 19 publications

(8 citation statements)

References 38 publications

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“…Ascorbate-induced lipid peroxidation was reported to increase in cyclosporine A-administered rats [22]. In kidney cortex mitochondria and microsomes, ascorbate was observed to increase cyclosporine A-induced lipid peroxidation and viability loss similar to the effect of ferrous iron [23]. However, pro-oxidant effects of ascorbate are not necessarily deleterious: accelerated DNA repair activity has been suggested to be induced by short-term co-supplementation of ascorbate plus a Fe(II)-salt to healthy volunteers [24].…”

Section: Pro-oxidant Effects Of Ascorbate Via Reduction Of Cellular mentioning

confidence: 78%

Vitamin C in Chronic Kidney Disease and Hemodialysis Patients

Deicher

Hörl

2003

Kidney Blood Press Res

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Increments of oxidative stress have been addressed as one potential cause for the accelerated atherosclerosis of chronic kidney disease patients. Ascorbate represents one of the most prominent antioxidants both in plasma as well as intracellulary, exerting beneficial effects by an inhibition of lipid peroxidation and by reducing endothelial dysfunction. However, in the presence of transition metals like iron, ascorbate may give rise to an increased generation of oxidants, and ascorbylation may impose additional carbonyl stress to uremic patients. Unsupplemented dialysis patients have reportedly lower plasma levels of ascorbate in comparison to healthy controls, mostly due to a loss into the dialysate or, in case of not dialyzed patients, increased urinary losses. Currently, 60 mg of ascorbate are recommended for chronic kidney disease patients, and 1–1.5 g of oral ascorbate/week in case of suspected subclinical ascorbate deficiency or 300 mg parenteral ascorbate/dialysis session, respectively. Ascorbate’s role in modifying arterial blood pressure remains unclear, but anemic patients with functional iron deficiency might benefit from short-term, moderately dosed ascorbate supplements.

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Section: Pro-oxidant Effects Of Ascorbate Via Reduction Of Cellular mentioning

confidence: 78%

Vitamin C in Chronic Kidney Disease and Hemodialysis Patients

Deicher

Hörl

2003

Kidney Blood Press Res

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“…The mechanisms of CsA nephrotoxicity are not well understood. CsA at high concentrations inhibits respiration and damages proteins and lipids in isolated mitochondria [17], [65], [66]. After in vivo treatment CsA decreases ATP levels in the rat kidney [19], [21].…”

Section: Discussionmentioning

confidence: 99%

Green Tea Polyphenols Stimulate Mitochondrial Biogenesis and Improve Renal Function after Chronic Cyclosporin A Treatment in Rats

et al. 2013

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Our previous studies showed that an extract from Camellia sinenesis (green tea), which contains several polyphenols, attenuates nephrotoxicity caused by cyclosporine A (CsA). Since polyphenols are stimulators of mitochondrial biogenesis (MB), this study investigated whether stimulation of MB plays a role in green tea polyphenol protection against CsA renal toxicity. Rats were fed a powdered diet containing green tea polyphenolic extract (0.1%) starting 3 days prior to CsA treatment (25 mg/kg, i.g. daily for 3 weeks). CsA alone decreased renal nuclear DNA-encoded oxidative phosphorylation (OXPHOS) protein ATP synthase-β (AS-β) by 42%, mitochondrial DNA (mtDNA)-encoded OXPHOS protein NADH dehydrogenase-3 (ND3) by 87% and their associated mRNAs. Mitochondrial DNA copy number was also decreased by 78% by CsA. Immunohistochemical analysis showed decreased cytochrome c oxidase subunit IV (COX-IV), an OXPHOS protein, in tubular cells. Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, the master regulator of MB, and mitochondrial transcription factor-A (Tfam), the transcription factor that regulates mtDNA replication and transcription, were 42% and 90% lower, respectively, in the kidneys of CsA-treated than in untreated rats. These results indicate suppression of MB by chronic CsA treatment. Green tea polyphenols alone and following CsA increased AS-β, ND3, COX-IV, mtDNA copy number, PGC-1α mRNA and protein, decreased acetylated PGC-1α, and increased Tfam mRNA and protein. In association with suppressed MB, CsA increased serum creatinine, caused loss of brush border and dilatation of proximal tubules, tubular atrophy, vacuolization, apoptosis, calcification, and increased neutrophil gelatinase-associated lipocalin expression, leukocyte infiltration, and renal fibrosis. Green tea polyphenols markedly attenuated CsA-induced renal injury and improved renal function. Together, these results demonstrate that green tea polyphenols attenuate CsA-induced kidney injury, at least in part, through the stimulation of MB.

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“…Later studies confirmed these observations, showing that large ascorbic acid doses did not produce kidney stones but, also, reduced the risk of kidney stone formation, concluding the ascorbic acid restriction, due to possibility of kidney stones formation, is unwarranted [86][87][88]. Pro-oxidative effects have been described in vitro for vitamin C in the presence of transition metal such as iron and copper [92]. Iron, through Fenton reaction, generates the highly reactive hydroxyl radical.…”

Section: Toxicological Considerationsmentioning

confidence: 87%

A short overview of vitamin C and selected cells of the immune system

Pavlović

Saraç

2010

Open Medicine

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AbstractVitamin C (ascorbic acid) is an essential water-soluble nutrient that primarily exerts its effect on a host defense mechanisms and immune homeostasis and is the most important physiological antioxidant. Stable intake of vitamin C is essential for life in humans because the body does not synthesize it. Even the numerous studies have demonstrated that vitamin C supplementation stimulates the immune system, prevents DNA damage and significantly decreases the risk of a wide range of pathologies; the potential protective mechanisms are still largely unknown. This review summarizes the recently known facts about the role of vitamin C on the selected cells of the immune system and potential molecular mechanisms involved. Further, in this review, many new data about the positive effects of vitamin C on the immune system, potential toxicological effects, vitamin C supplementation in disease development, as well as some proposed mechanisms of vitamin C activity, are discussed.

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Effect of iron and ascorbate on cyclosporine-induced oxidative damage of kidney mitochondria and microsomes

Cited by 19 publications

References 38 publications

Vitamin C in Chronic Kidney Disease and Hemodialysis Patients

Vitamin C in Chronic Kidney Disease and Hemodialysis Patients

Green Tea Polyphenols Stimulate Mitochondrial Biogenesis and Improve Renal Function after Chronic Cyclosporin A Treatment in Rats

A short overview of vitamin C and selected cells of the immune system

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