Cyclosporine reduces hepatic antioxidant capacity: protective roles of antioxidants

Durak, İlker; Özbek, Hanefí; Elgün, Serenay

doi:10.1016/j.intimp.2004.01.018

Cited by 39 publications

(31 citation statements)

References 16 publications

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“…Hepatotoxicity induced by CsA administration is widely reported in literature (Wolf et al 1997, Durak et al 2004, Hagar 2004, Rezzani 2004, 2005a, 2006, Kurus et al 2008, Bohmer et al 2011. There are two possible mechanisms of CsAinduced hepatotoxicity: (1) due to an excess of free radical production during CsA metabolism in the liver; or (2) CsA may impair the antioxidant defense (Durak et al 2004).…”

Section: Discussionmentioning

confidence: 99%

“…There are two possible mechanisms of CsAinduced hepatotoxicity: (1) due to an excess of free radical production during CsA metabolism in the liver; or (2) CsA may impair the antioxidant defense (Durak et al 2004). Rezzani et al (2005a) suggested that the oxidative stress induced by CsA is associated with the imbalance of free oxygen radical production and the antioxidant defense system.…”

Section: Discussionmentioning

confidence: 99%

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The effects of Cyclosporin A and Heteropterys tomentosaon the rat liver

Freitas

Almeida

Monteiro

et al. 2015

An. Acad. Bras. Ciênc.

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Cyclosporin A (CsA) is a widely employed immunosuppressive drug that is associated with several side effects, among then hepatotoxicity. Heteropterys tomentosa is a Brazilian plant efficient in reducing damage caused by CsA on the rat testis and prostate. The aim of this study was to evaluate the effect of CsA and H. tomentosa (administered isolated or simultaneously) on the liver of Wistar rats. The animals were treated daily with water (control), CsA (15mg/kg/day), H. tomentosa infusion or CsA+H. tomentosa, for 21 or 56 days. The treatments did not alter liver morphology or cause fibrosis. H. tomentosa administered for 21 days increased the number of hepatocyte nuclei and Kupffer cell volumetric proportion. After 56 days of treatment, H. tomentosa administration did not alter the parameters analyzed. Biochemical plasma dosages and liver stereology showed impairment caused by CsA-treatment after 21 days; these results were not observed after 56 days of treatment. The simultaneous treatment with CsA and H. tomentosa for 21 or 56 days did not alleviate nor accentuate CsA hepatic effects. The present study showed that the 21 days treatment with CsA caused more alteration to the liver than the 56 days treatment; this could be related to hepatic recovery after the long term treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The effects of Cyclosporin A and Heteropterys tomentosaon the rat liver

Freitas

Almeida

Monteiro

et al. 2015

An. Acad. Bras. Ciênc.

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“…The mechanisms of CsA-induced hepatotoxicity are not fully elucidated. However, increased production of reactive oxygen species (ROS) and a consequent imbalance between oxidants and endogenously produced antioxidants have been reported to play an important role in CsA-induced hepatotoxicity (Durak et al, 2004;Hagar, 2004;Rezzani, 2006). ROS induced by CsA can be antagonized by using a powerful antioxidant agent (Kaya et al, 2008;Rezzani, 2006).…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of the protective role of wheat germ oil against cyclosporin A-induced hepatotoxicity in rats

Akool

2015

Pharmaceutical Biology

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Context: Cyclosporin A (CsA) is one of the most important immunosuppressive agents. However, its clinical use is strongly limited by several side effects including hepatotoxicity which remains a major clinical problem. Involvement of reactive oxygen species (ROS) in CsAinduced hepatotoxicity has been reported. Objective: This study investigates the potential protective role of wheat germ oil (WGO) as an antioxidant against CsA-induced hepatotoxicity. Materials and methods: Twenty-four male Wistar albino rats (six animals in each group) received castor oil, the vehicle of CsA i.p. (control) or either CsA (25 mg/kg/d i.p.), WGO (900 mg/kg/d by oral gavage), or CsA in combination with WGO daily for 21 d. Results: CsA administration significantly increased serum levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, an increase in lipid peroxidation, inducible NO-synthase (iNOS), and NF-kB expression were observed in hepatic tissues of CsA-alone-treated rats. Furthermore, significant reduction in the hepatic content of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) was also observed in CsA-alone-treated animals. Moreover, histopathological changes occurred in CsA-alonetreated rats. Concomitant administration of WGO along with CsA improved all these parameters. Most interestingly, the immunosuppressive effect of CsA was not affected by WGO. Conclusion: The present study suggests that concomitant use of WGO might be useful in reducing liver toxicity induced by CsA via inhibition of ROS, iNOS, and NF-kB expression.

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“…45 MDA is one of the most important end products of lipid peroxidation and is known to be an indicator of free radical damage and also indirectly of tissue damage. 46 Durak et al 47 have shown that decrease in glutathione and accumulation of MDA are important mechanisms in CsA-induced toxicity.…”

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confidence: 99%

Protective effect of trapidil andl-arginine against renal and hepatic toxicity induced by cyclosporine in rats

Salem

Maarouf

et al. 2010

Renal Failure

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(2010) Protective effect of trapidil and l-arginine against renal and hepatic toxicity induced by cyclosporine in rats, Renal Failure, 32:8,[959][960][961][962][963][964][965][966][967][968] DOI: 10.3109 CsA induced renal and hepatic dysfunction, which was confirmed by laboratory and histopathological examination. Administration of trapidil diminished the renal and liver injury and significantly attenuated the levels of serum creatinine, urea, aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin1b (IL-1b), tumor necrosis factor alpha (TNF-a), monocyte chemoattractant protein-1 (MCP-1), and oxidative stress, while it significantly elevated the level of serum nitric oxide and the activity of antioxidative stress. L-Arginine gave the same trend as trapidil, but trapidil effect was more pronounced. Coadministration of trapidil + L-arginine significantly ameliorated the toxic effect of CsA, but did not differ significantly from the effect of trapidil alone. Conclusions: Treatment with trapidil or L-arginine diminished the renal and hepatic CsA-induced toxicity. However, the effect of trapidil was more pronounced. Therefore, treatment with trapidil alone may be the most economic and effective as a potential therapeutic agent in CsA injury.

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Cyclosporine reduces hepatic antioxidant capacity: protective roles of antioxidants

Cited by 39 publications

References 16 publications

The effects of Cyclosporin A and Heteropterys tomentosaon the rat liver

The effects of Cyclosporin A and Heteropterys tomentosaon the rat liver

Molecular mechanisms of the protective role of wheat germ oil against cyclosporin A-induced hepatotoxicity in rats

Protective effect of trapidil andl-arginine against renal and hepatic toxicity induced by cyclosporine in rats

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