Evidence That Alterations in Renal Metabolism and Lipid Peroxidation May Contribute to Cyclosporine Nephrotoxicity

Walker, Robert; Lazzaro, V. A.; Duggin, Geoffrey G.; Horvath, John S.; Tiller, David J.

doi:10.1097/00007890-199009000-00025

Cited by 61 publications

(15 citation statements)

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“…Both SAC and vitamin C improved the renal function, with more pronounced eff ect observed in SAC-treated animals. The increased levels of TBARS indicate excessive formation of free radicals by CsA induction and activation of the lipid peroxidative process, resulting in irreversible damage to renal tissue in animals subjected to CsA stress (Walker et al, 1990;Longoni et al, 1999). SAC treatment signifi cantly decreased the LPO levels by preventing formation of lipid peroxides from fatty acids.…”

Section: Discussionmentioning

confidence: 99%

S‐allylcysteine attenuates renal injury by altering the expressions of iNOS and matrix metallo proteinase‐2 during cyclosporine‐induced nephrotoxicity in Wistar rats

Mani¹,

Umesalma²,

Srinivasan³

et al. 2009

J of Applied Toxicology

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Cyclosporine A (CsA) is the first choice immunosuppressant used for the prevention of allograft rejection in solid organ transplantation and immune-mediated diseases. Reactive oxygen species-induced oxidative stress and lipid peroxidation are implicated in the pathophysiology of CsA-induced renal injury. In this work, we have studied the effect of a garlic-derived compound, S-allylcysteine (SAC) on CsA-induced nephrotoxicity. CsA-induced nephrotoxicity was assessed in terms of increased activities of serum marker enzymes and levels of kidney markers. CsA administration induced significant elevation in lipid peroxidation along with abnormal levels of enzymic and non-enzymic antioxidants in the kidneys of the rats. SAC administration improved renal function by bringing about a significant decrease in peroxidative levels and increase in antioxidant status. Elevated expressions of inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-kappaB) due to CsA administration were reduced by SAC treatment. An increase in the expression of matrix metalloproteinase-2 (MMP-2) was evident in CsA-induced groups of rats, which was moderately reduced in SAC treated rats. An increase in the levels of serum constituent's urea, uric acid and creatinine was observed in the CsA-induced rats, which was reduced upon treatment with SAC. These results indicate that SAC has a protective action against CsA-induced nephrotoxicity which is also supported by histopathological studies. A comparative study of the antioxidant vitamin C and SAC is more valuable to assess the efficacy of the drug that can be used for the treatment of nephrotoxicity.

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Section: Discussionmentioning

confidence: 99%

S‐allylcysteine attenuates renal injury by altering the expressions of iNOS and matrix metallo proteinase‐2 during cyclosporine‐induced nephrotoxicity in Wistar rats

Mani¹,

Umesalma²,

Srinivasan³

et al. 2009

J of Applied Toxicology

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“…Although the mechanisms of nephrotoxicity are not completely defined, there is evidence suggesting that the role of oxidative stress and the generation of oxygen free radicals are increasingly considered as an important factor involved in CsA nephrotoxicity [17]. For example, reactive oxygen species (ROS) have been implicated in models of acute renal failure induced by gentamicin [18], cisplatin [19], and CsA in animals [20].…”

Section: Discussionmentioning

confidence: 99%

“…Various studies have shown that increased lipid peroxidation accompanies loss of renal function in CsA-induced nephrotoxicity [29, 30]. NSO significantly attenuated the increase of MDA concentration in the kidney tissue, possibly by preventing oxidant reactions.…”

Section: Discussionmentioning

confidence: 99%

<i>Nigella sativa</i> Oil for Prevention of Chronic Cyclosporine Nephrotoxicity: An Experimental Model

Uz¹,

Bayrak²,

Uz³

et al. 2008

Am J Nephrol

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Nephrotoxicity is the main secondary effect of cyclosporine A (CsA) treatment. The antioxidant action of Nigella sativa oil (NSO) may explain the protective effect of these agents against various hepatotoxic and nephrotoxic models in vivo and in vitro. This study was designed to investigate the possible protective effects of NSO, in prevention of chronic CsA-induced nephrotoxicity in rats. Animals were randomly divided into four experimental groups: the control group received sunflower oil, the other groups were treated with CsA (25 mg/kg/day b.w. orally) or NSO (2 ml/kg orally) or CsA + NSO, respectively. Urine and serum creatinine levels, tissue superoxide dismutase, glutathione peroxidase and catalase enzyme activities, and nitric oxide and malondialdehyde levels were measured, and histological examination was performed. In our study, CsA caused a significant deterioration in the renal function, morphology and gave rise to severe oxidative stress in the kidney. NSO significantly improved the functional and histological parameters and attenuated the oxidative stress induced by CsA. In conclusion, our study demonstrated for the first time that NSO protects kidney tissue against oxygen free radicals, preventing renal dysfunction and morphological abnormalities associated with chronic CsA administration.

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“…In such studies (in general using short-term Cy A treatment), the GSSG increase was accompanied by unchanged or decreased GSH levels. The resulting increased ratio of oxidized GSH to total GSH [1,2] points towards an imbalance in oxygen radical metabolism after short-time Cy A treatment that could have facilitated the lipid peroxidation demonstrated in these studies. According to our study design, a similar but temporary effect of Cy A may have arisen immediately after onset of the treatment.…”

Section: Discussionmentioning

confidence: 82%

“…It has been suggested that Cy A-induced oxidative stress could be responsible for the nephrotoxicity and hepatotoxicity of this drug [1][2][3]. Recently, Tatou et al demonstrated an increased formation of lipid peroxides in isolated rat heart during ischemia/ reperfusion experiments in the presence of Cy A [4].…”

Section: Introductionmentioning

confidence: 99%

Differential response of oxygen radical metabolism in rat heart, liver and kidney to cyclosporine A treatment

Haberland

Henke

Grune

et al. 1997

Inflammation Research

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Evidence That Alterations in Renal Metabolism and Lipid Peroxidation May Contribute to Cyclosporine Nephrotoxicity

Cited by 61 publications

References 0 publications

S‐allylcysteine attenuates renal injury by altering the expressions of iNOS and matrix metallo proteinase‐2 during cyclosporine‐induced nephrotoxicity in Wistar rats

S‐allylcysteine attenuates renal injury by altering the expressions of iNOS and matrix metallo proteinase‐2 during cyclosporine‐induced nephrotoxicity in Wistar rats

<i>Nigella sativa</i> Oil for Prevention of Chronic Cyclosporine Nephrotoxicity: An Experimental Model

Differential response of oxygen radical metabolism in rat heart, liver and kidney to cyclosporine A treatment

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