Provinol Prevents CsA-induced Nephrotoxicity by Reducing Reactive Oxygen Species, iNOS, and NF-kB Expression

Buffoli, Barbara; Pecháňová, Oľga; Kojsová, Stanislava; Andriantsitohaina, Ramaroson; Giugno, Lorena; Bianchi, Rossella; Rezzani, Rita

doi:10.1369/jhc.5a6623.2005

Cited by 50 publications

(41 citation statements)

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“…Together these data suggest that the protective role played by PV involves the same biochemical pathway observed in CsA-treated adult rats, and we could therefore propose a similar mechanism. In fact, as proposed by Buffoli et al (2005), red wine polyphenols protect renal damage due to oxidative stress and prevent NF-kB expression during immunosuppressive treatment. This downregulation produces a decrease of iNOS expression.…”

Section: Discussionmentioning

confidence: 94%

“…These groups were treated during pregnancy from day 0 to day 21. In particular, group I was injected SC with olive oil, the CsA vehicle; group II was treated with oral administration of PV (40 mg/kg/day; Socie´teF rancaise de Distillerie, Vallont Pont d'Arc, France) according to Buffoli et al (2005). These animals were used as control groups.…”

Section: Animals and Experimental Treatmentsmentioning

confidence: 99%

“…To help to address these questions we studied the activity and expression of two proteins responsible for CsA nephrotoxicity in adult rats: inducible nitric oxide synthase (iNOS, NOS2) (Rezzani et al 2003;Buffoli et al 2005) and matrix metalloproteinase-2 (MMP2) (Eberhardt et al 2000;Khanna et al 2002).…”

mentioning

confidence: 99%

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Protective Role of Polyphenols in Cyclosporine A-induced Nephrotoxicity During Rat Pregnancy

Rezzani

Rodella

Tengattini

et al. 2006

J Histochem Cytochem.

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The aim of this study was to evaluate the adverse effects of cyclosporine A (CsA) toward renal morphogenesis and to test the renoprotective natural antioxidants such as provinol (PV). Pregnant rats were divided into four groups. Group I was injected SC with olive oil. Group II was treated with oral administration of PV and was used as control. Group III animals were injected SC daily with CsA, and group IV animals were injected daily with CsA and PV for 21 days of pregnancy. Five pups per litter were killed and the kidneys removed and treated by morphological and immunohistochemical (IHC) methods. IHC analysis considered two proteins responsible for nephrotoxicity in adult rats: inducible nitric oxide (iNOS) and matrix metalloproteinase-2 (MMP2). Pregnancy outcomes among CsA-treated rats demonstrated a reduced number of pups. Pups that were exposed antenatally to CsA presented several pathologic findings in all immature parenchyma and an increase in iNOS and MMP2 expression. These side effects were not observed in kidney of litters born from CsA + PV-treated mothers. Our study indicates that CsA induces morphological alterations in renal parenchyma of neonates and that PV plays a protective role against these side effects.

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Section: Discussionmentioning

confidence: 94%

Section: Animals and Experimental Treatmentsmentioning

confidence: 99%

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Protective Role of Polyphenols in Cyclosporine A-induced Nephrotoxicity During Rat Pregnancy

Rezzani

Rodella

Tengattini

et al. 2006

J Histochem Cytochem.

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“…The administrations of CsA for 21 (Buffoli et al 2005, Rezzani et al 2005a, b, Türk et al 2007 or 56 days (Monteiro et al 2008, Freitas et al 2012a, 2013 were chosen based on previous experiments reported in literature.…”

Section: Experimental Animals and Protocolmentioning

confidence: 99%

“…However, several side effects are associated with CsA treatment such as: nephrotoxicity (Bertani et al 1987, Baliga et al 1997, Fellstrom 2004, Rezzani 2004, Hagar et al 2006, Josephine et al 2006, Rezzani et al 2006b), hepatotoxicity (Durak 370 KARINE M. DE FREITAS et al et al 2004, Hagar 2004, Rezzani 2004, 2006, Kurus et al 2008, Bohmer et al 2011, testicular dysfunction (Monteiro et al 2008) and damages to the ventral prostate (Freitas et al 2012a). Most of these are related to the increase of reactive oxygen species (Wolf et al 1997, Buffoli et al 2005, Rezzani 2006, causing damage to tissue structure and functional disorders (Whiting et al 1983). Several researchers have investigated substances that reduce CsA side effects (Rezzani et al 2001, 2006a, b, Parra Cid et al 2003, Monteiro et al 2008, Wongmekiat et al 2008.…”

Section: Introductionmentioning

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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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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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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Provinol Prevents CsA-induced Nephrotoxicity by Reducing Reactive Oxygen Species, iNOS, and NF-kB Expression

Cited by 50 publications

References 50 publications

Protective Role of Polyphenols in Cyclosporine A-induced Nephrotoxicity During Rat Pregnancy

Protective Role of Polyphenols in Cyclosporine A-induced Nephrotoxicity During Rat Pregnancy

The effects of Cyclosporin A and Heteropterys tomentosaon the rat liver

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

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