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

Ishikawa, Akira; Homma, Yukio

doi:10.1590/s1677-55382012000200011

Cited by 8 publications

(6 citation statements)

References 21 publications

(18 reference statements)

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“…Oxidative stress is a key contributor to the pathogenesis of CSA‐induced organ damage and dysfunction (El‐Mas et al ., 2011; 2012; de Arriba et al ., ). The current observation that CSA caused significant elevations in the renal content of MDA, the lipid peroxidation product of oxidative destruction of polyunsaturated fatty acids of biological membranes, is in line with the established role of oxidative stress caused by lipid peroxides in CSA‐induced nephrotoxicity (Ishikawa and Homma, ). Alternatively, the concomitant increase in renal GSH might presumably constitute a feedback mechanism to offset the progression in oxidative damage caused by CSA (Helmy and El‐Gowelli, ).…”

Section: Discussionsupporting

confidence: 82%

Endothelin ET_A receptor/lipid peroxides/COX‐2/TGF‐β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats

Helmy

El‐Gowelli

Ali

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSECyclosporine (CSA) and non-steroidal anti-inflammatory drugs (NSAIDs) are co-prescribed for some arthritic conditions. We tested the hypothesis that this combined regimen elicits exaggerated nephrotoxicity in rats via the up-regulation of endothelin (ET) receptor signalling. EXPERIMENTAL APPROACHThe effects of a 10 day treatment with CSA (20 mg·kg ) or their combination on renal biochemical, inflammatory, oxidative and structural profiles were assessed. The roles of ETA receptor and COX-2 pathways in the interaction were evaluated. KEY RESULTSOral treatment with CSA or indomethacin elevated serum urea and creatinine, caused renal tubular atrophy and interstitial fibrosis, increased renal TGF-β1, and reduced immunohistochemical expressions of ETA receptors and COX-2. CSA, but not indomethacin, increased renal ET-1, the lipid peroxidation product malondialdehyde (MDA) and GSH activity. Compared with individual treatments, simultaneous CSA/indomethacin exposure caused: (i) greater elevations in serum creatinine and renal MDA; (ii) loss of the compensatory increase in GSH; (iii) renal infiltration of inflammatory cells and worsening of fibrotic and necrotic profiles; and (iv) increased renal ET-1 and decreased ETA receptor and COX-2 expressions. Blockade of ETA receptors by atrasentan ameliorated the biochemical, structural, inflammatory and oxidative abnormalities caused by the CSA/indomethacin regimen. Furthermore, atrasentan partly reversed the CSA/indomethacin-evoked reductions in the expression of ETA receptor and COX-2 protein. CONCLUSIONS AND IMPLICATIONSThe exaggerated oxidative insult and associated dysregulation of the ETA receptor/COX-2/TGF-β1 signalling might account for the aggravated nephrotoxicity caused by the CSA/indomethacin regimen. The potential renoprotective effect of ETA receptor antagonism might be exploited therapeutically.

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Section: Discussionsupporting

confidence: 82%

Endothelin ET_A receptor/lipid peroxides/COX‐2/TGF‐β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats

Helmy

El‐Gowelli

Ali

et al. 2015

British J Pharmacology

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“…CoQ 10 acts as a powerful antioxidant that scavenges free radicals, prevents lipid peroxidation in cellular biomembranes, and promotes a-tocophrol regeneration (5,6). Previous studies confirmed the protective effects of CoQ 10 in various models of oxidative injury (7)(8)(9)(10)(11)(12)(13)(14).…”

mentioning

confidence: 88%

Coenzyme Q ₁₀ alleviates tacrolimus‐induced mitochondrial dysfunction in kidney

Lim

Luo

et al. 2019

FASEB j.

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The major side effect of tacrolimus (Tac) is nephrotoxicity. We studied whether supplementation of coenzyme Q10, (CoQ10) a potent antioxidant, can reduce Tac‐induced nephrotoxicity via improving mitochondrial function. In an in vitro study, CoQ10 reduced the production of Tac‐induced mitochondrial reactive oxygen species and abolished the loss of mitochondrial membrane potential in proximal tubular cell line. Assessment of mitochondrial function revealed that CoQ10 decreased oxygen consumption and mitochondrial respiration rate increased by Tac, suggesting improvement of mitochondrial function to synthesize ATP with CoQ10 treatment. The effect of the CoQ10 in vitro study was observed in an experimental model of chronic Tac‐induced nephropathy. CoQ10 attenuated Tac‐induced oxidative stress and was accompanied by function and histologic improvement. On electron microscopy, addition of CoQ10 increased not only the number but also the volume of mitochondria compared with Tac treatment only. Our data indicate that CoQ10 improves Tac‐induced mitochondrial dysfunction in kidney. Supplementary CoQ10 treatment may be a promising approach to reduce Tac‐induced nephrotoxicity.—Yu, J. H., Lim, S. W., Luo, K., Cui, S., Quan, Y., Shin, Y. J., Lee, K. E., Kim, H. L., Ko, E. J., Chung, B. H., Kim, J. H., Chung, S. J., Yang, C. W. Coenzyme Q10 alleviates tacrolimus‐induced mitochondrial dysfunction in kidney. FASEB J. 33, 12288‐12298 (2019). http://www.fasebj.org

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“…18 The anti-oxidative and anti-inflammatory potential of CoQ10 was reported to be beneficial for the nephropathy induced by cisplatin or cyclosporine. 19,20 It has been suggested that some types of antioxidants have health benefits that fight cyclophosphamide-induced toxicity in lung tissue. However, the effectiveness of coenzyme Q10 as a protective role against oxidative injury varies greatly according to the physiological status of animals, health and disease of animals, concentration and period of dietary CoQ10 supplementation, interaction with other nutrients, etc.…”

Section: Introductionmentioning

confidence: 99%

The potential protective role of coenzyme q10 on the cyclophosphamide-induced lung toxicity in adult male albino rats: a histological and ultrastructural study

2018

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Background: Cyclophosphamide is anticancer and immunosuppressant agent used to treat malignant and autoimmune diseases. Its long-term use causes side effects, as infertility and pulmonary toxicity. Coenzyme Q10; the only synthesized antioxidant in human body, acts as powerful antioxidant, scavenging free radicals, and inhibiting lipid peroxidation. Aim of present study was to examine effect of coenzyme Q10 on blood biochemical profiles, histopathological changes in lungs of adult rats exposed to cyclophosphamide-induced toxicity.Methods: 36 adult male albino rats divided into four groups; control and three experimental each having 9 rats. First experimental group received coenzyme Q10, second received cyclophosphamide while third group received coenzyme Q10 along with cyclophosphamide. Experiment lasted for 7 days. On 8th day, animals were sacrificed by decapitation. Lung tissue samples were collected for histopathological examination. SOD (superoxide dismutase) and MDA (malondialdehyde) levels were determined and used for statistical analysis. Results: In coenzyme Q10 treated group, H&E stained sections revealed normal respiratory alveoli. Ultrathin sections revealed normal alveolar septa, pneumocyte and blood capillaries contain erythrocytes. In cyclophosphamide treated group, H&E stained sections revealed peribronchial and interstitial fibrosis. Ultrathin sections revealed alveoli having apparent free lumen with extravasated erythrocytes. Alveolar septa revealed collagen fibrils deposits, and proliferated fibroblasts. In combined coenzyme Q10 and cyclophosphamide treated group, H&E stained sections revealed marked decrease of inter-alveolar tissue thickening. Ultrathin sections revealed destructed alveolar septa with dissociated remnants of collagen fibrils. Blood capillaries appeared wide, containing monocytes and erythrocytes.Conclusions: Administration of coenzyme Q10 with cyclophosphamide is advised to alleviate cyclophosphamide-induced lung toxicity.

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

Abstract: ARTICLE INFO ___________________________________________ _

Cited by 8 publications

References 21 publications

Endothelin ET_A receptor/lipid peroxides/COX‐2/TGF‐β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats

Endothelin ET_A receptor/lipid peroxides/COX‐2/TGF‐β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats

Coenzyme Q ₁₀ alleviates tacrolimus‐induced mitochondrial dysfunction in kidney

The potential protective role of coenzyme q10 on the cyclophosphamide-induced lung toxicity in adult male albino rats: a histological and ultrastructural study

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

Abstract: ARTICLE INFO _______________________________________________________________ _____________________

Cited by 8 publications

References 21 publications

Endothelin ETA receptor/lipid peroxides/COX‐2/TGF‐β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats

Endothelin ETA receptor/lipid peroxides/COX‐2/TGF‐β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats

Coenzyme Q 10 alleviates tacrolimus‐induced mitochondrial dysfunction in kidney

The potential protective role of coenzyme q10 on the cyclophosphamide-induced lung toxicity in adult male albino rats: a histological and ultrastructural study

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Abstract: ARTICLE INFO ___________________________________________ _

Endothelin ET_A receptor/lipid peroxides/COX‐2/TGF‐β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats

Endothelin ET_A receptor/lipid peroxides/COX‐2/TGF‐β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats

Coenzyme Q ₁₀ alleviates tacrolimus‐induced mitochondrial dysfunction in kidney