In vivo effect of the natural antioxidant hydroxytyrosol on cyclosporine nephrotoxicity in rats

Capasso, Giovambattista; Gennaro, Chiara Iolanda Di; Ragione, Fulvio Della; Manna, Caterina; Ciarcia, Roberto; Florio, Salvatore; Perna, Angelica; Pollastro, Rosa Maria; Damiano, Sara; Mazzoni, Orazio; Galletti, Patrizia; Zappia, Vincenzo

doi:10.1093/ndt/gfm784

Cited by 56 publications

(40 citation statements)

References 36 publications

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“…Several previous studies had suggested that cyclosporine nephrotoxicity may be improved or prevented by antioxidants. [12][13][14][15][16][17] A meta-analysis of clinical trials of CoQ10 for hypertension concluded that CoQ10 had potential for lowering blood pressure in hypertensive patients 18 ; however, in this study, no significant reduction of systolic blood pressure was observed when rCoQ10 was administered with cyclosporine. A possible explanation for this finding is that cyclosporine-induced hypertension may be caused by activation of the intrarenal renin-angiotensin axis, 7 but the renal protective effect of rCoQ10 may be accomplished by another mechanism.…”

Section: Discussioncontrasting

confidence: 60%

Effect of Reduced Form of Coenzyme Q10 on Cyclosporine Nephrotoxicity

Sato

Ishikawa²,

Homma³

2012

Exp Clin Transplant

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Objectives: Cyclosporine, a potent immunosuppressant, has nephrotoxic adverse effects that may be mediated by oxidative stress. The reduced form of coenzyme Q10 has antioxidant effects. The aim of the present study was to evaluate the effect of the reduced form of coenzyme Q10 on cyclosporine nephrotoxicity. Materials and Methods: Six-week-old male Wistar rats were divided into 3 groups (10 animals each). Group 1 (control) received olive oil only. Group 2 received cyclosporine (30 mg/kg/d, which is an experimentally nephrotoxic dose). Group 3 received cyclosporine (30 mg/kg/d) and the reduced form of coenzyme Q10 (600 mg/kg/d). The cyclosporine and the reduced form of coenzyme Q10 were given orally for 4 weeks. Daily urinary albumin excretion, serum creatinine level, and urinary 8-hydroxydeoxyguanosine level were measured, and renal tissue was evaluated by immunohis tochemistry. Results: In rats treated with cyclosporine and the reduced form of coenzyme Q10 (group 3), there were significantly less abnormalities in mean urinary albumin excretion (group 1: 2.8 ± 0.5; group 2: 41 ± 7; group 3: 21 ± 4 µg/d), serum creatinine (group 1: 1.0 ± 0.2; group 2: 1.8 ± 0.4; group 3: 1.4 ± 0.3 mg/dL), and urine 8-hydroxydeoxyguanosine levels (group 1: 7 ± 3; group 2: 10 ± 3; group 3: 7 ± 1 mg/mL creatinine) than rats treated with cyclosporine alone (group 2). There were 8-hydroxydeoxyguanosine deposits seen in the proximal tubular cells of group 2 that were not present in rats treated with the reduced form of coenzyme Q10 (group 3). Conclusions: The reduced form of coenzyme Q10 may prevent or minimize cyclosporine nephrotoxicity by an antioxidant effect.

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Section: Discussioncontrasting

confidence: 60%

Effect of Reduced Form of Coenzyme Q10 on Cyclosporine Nephrotoxicity

Sato

Ishikawa²,

Homma³

2012

Exp Clin Transplant

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“…RCoQ10 also diminished TGF-beta expression in the proximal renal tubular cells. There are several animal and clinical studies suggesting that antioxidative agents have some preventive effect of CyA nephrotoxicity (7)(8)(9)(10)(11)(12). In 2004, Dlugosz et al reported the benefit of CoQ10 on renal transplant recipients for the first time (13); however, they used ubiquinone, the oxidized form of CoQ10.…”

Section: Discussionmentioning

confidence: 99%

Beneficial effect of ubiquinol, the reduced form of coenzyme Q10, on cyclosporine nephrotoxicity

Ishikawa

Homma

2012

Int. braz j urol.

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“…For tubular injury, the following score was used: 0 ¼ no tubular injury; 1 ¼ <25% of tubules injured; 2 ¼ from 25 to 50% of tubules injured; 3 ¼ from 51 to 75% of tubules injured; 4 ¼ more than 76% of tubules injured. 19 Measurements of Renal MDA Levels, SOD, ACE, Ang II, and NADPH Oxidase Activities…”

Section: Renal Histopathological Examinationmentioning

confidence: 99%

Aged Rats Are Susceptible to Nephrotoxicity Induced by Iodinated Contrast Media

et al. 2012

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Objective: The objective of this study is to evaluate the effect and mechanism of aging on iodinated-contrast-mediainduced nephropathy in male rats. Methods: Twenty-four healthy male rats were initially divided into 12-month-old and 24-month-old age groups (adult and older age groups, respectively; n ¼ 12/group); subsequently, each age group was randomly divided into saline control (NS) and contrast media (CM) groups (n ¼ 6/group). CM (76% diatrizoate, 10 mL/kg b.w.) was given through the caudal vein. Urinary creatinine (Ucr) and serum creatinine (Scr) were detected by an automatic biochemical analyzer. The activities of renal malondialdehyde (MDA), superoxide dismutase (SOD), angiotensinconverting enzyme (ACE), angiotensin II (Ang II), and reduced form of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) were determined by spectrophotometric assays with commercially available kits according to the manufacturers' protocols. Renal histological changes were observed by hematoxylin and eosin staining and scored semiquantitatively. Results: In diatrizoate-injected aged rats, Scr, the activities of ACE, Ang II, MDA, and NADPH oxidase in renal tissues were significantly increased (p < 0.01). The histologic scores were higher in the aged animals with CM treatment than those of control or adult rats (p < 0.01). There was an increasing trend but no significant statistical difference in renal ACE, Ang II, MDA, and NADPH oxidase or histologic scores in adult CM-injected rats compared with control animals (p > 0.05). Conclusions: Older age is an aggravating factor of iodinated-contrast-media-induced nephropathy in male rats. Oxidative stress and the renin-angiotensin system (RAS) may play an important role in nephrotoxicity induced by iodinated contrast media, especially in aged male rats.

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In vivo effect of the natural antioxidant hydroxytyrosol on cyclosporine nephrotoxicity in rats

Cited by 56 publications

References 36 publications

Effect of Reduced Form of Coenzyme Q10 on Cyclosporine Nephrotoxicity

Effect of Reduced Form of Coenzyme Q10 on Cyclosporine Nephrotoxicity

Beneficial effect of ubiquinol, the reduced form of coenzyme Q10, on cyclosporine nephrotoxicity

Aged Rats Are Susceptible to Nephrotoxicity Induced by Iodinated Contrast Media

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