Cyclosporine A-induced acute hepatotoxicity in guinea pigs is associated with endothelin-mediated decrease in local hepatic blood flow

Erdem, Remzi; Emre-Aydıngöz, Selda; Atilla, Pergin; Çakar, Ayşe Nur; Dalkara, Turgay; Bolay, Hayrünnisa; Tuncer, Meral

doi:10.1016/j.lfs.2011.02.015

Cited by 11 publications

(8 citation statements)

References 33 publications

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“…Our findings revealed that administration of CsA increased levels of AST, ALT, and bilirubin and these findings are consistent with the results of experimental studies of other authors, which show that elevated levels of these parameters evidence functional liver damage [ 8 , 23 – 27 ].…”

Section: Discussionsupporting

confidence: 93%

“…Congestion and widening of hepatic sinuses, activation of Kupffer cells, passive congestion and swelling in the portal tracts, mild inflammatory mononuclear cell infiltrates within the portal tracts, and hepatocyte degenerative changes, vacuolar degeneration and steatosis, were present. Similar findings have also been described in other experimental studies [ 10 – 12 , 24 , 27 , 40 ] demonstrating focal necrosis of hepatocytes and the presence of apoptotic cells [ 10 – 12 , 40 ].…”

Section: Discussionsupporting

confidence: 91%

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Oxidative Stress and Liver Morphology in Experimental Cyclosporine A-Induced Hepatotoxicity

Korolczuk

Caban

Amarowicz

et al. 2016

BioMed Research International

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Cyclosporine A is an immunosuppressive drug used after organ's transplantation. The adverse effects on such organs as kidney or liver may limit its use. Oxidative stress is proposed as one of the mechanisms of organs injury. The study was designed to elucidate CsA-induced changes in liver function, morphology, oxidative stress parameters, and mitochondria in rat's hepatocytes. Male Wistar rats were used: group A (control) receiving physiological saline, group B cyclosporine A in a dose of 15 mg/kg/day subcutaneously, and group C the CsA-vehicle (olive oil). On the 28th day rats were anesthetized. The following biochemical changes were observed in CsA-treated animals: increased levels of ALT, AST, and bilirubin in the serum, statistically significant changes in oxidative stress parameters, and lipid peroxidation products in the liver supernatants: MDA+4HAE, GSH, GSSG, caspase 3 activity, and ADP/ATP, NAD+/NADH, and NADP+/NADPH ratios. Microscopy of the liver revealed congestion, sinusoidal dilatation, and focal hepatocytes necrosis with mononuclear cell infiltration. Electron microscope revealed marked mitochondrial damage. Biochemical studies indicated that CsA treatment impairs liver function and triggers oxidative stress and redox imbalance in rats hepatocytes. Changes of oxidative stress markers parallel with mitochondrial damage suggest that these mechanisms play a crucial role in the course of CsA hepatotoxicity.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Oxidative Stress and Liver Morphology in Experimental Cyclosporine A-Induced Hepatotoxicity

Korolczuk

Caban

Amarowicz

et al. 2016

BioMed Research International

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“…Semiquantitative histologic scoring suggested that liver changes were significantly higher in the CsA group than other treatment or control groups. In accordance with our results, Erdem et al [4] reported swelling and vacuolization in hepatocytes after CsA-administration in guinea pigs, and Eraslan et al [8] and Kurus et al [7,12] also found that sinusoidal dilatation, cell infiltration, congestion, and hepatocellular vacuolization occurs after CsA-induced liver damage. In contrast, Bohmer et al [25] did not find histopathologic changes in liver after CsA treatment.…”

Section: Discussionsupporting

confidence: 92%

“…These findings are consistent with previously published reports. For example, Hagar [2] demonstrated that high AST and ALT levels were detected in CsAinduced hepatotoxic rats, and Erdem et al [4] showed the AST, ALP, and TBil levels were higher in CsA-treated guinea pigs than in animals from the control group (however, ALT levels appeared unaffected in this study). In further studies by Eraslan et al [8], Pari and Sivasankari [5], and Kurus et al [7], serum levels of both ALT and AST, as well as of ALP, were shown to be increased in the CsA-treated animals.…”

Section: Discussioncontrasting

confidence: 42%

Effects of antioxidant agents against cyclosporine-induced hepatotoxicity

Akbulut

Elbe

Eris

et al. 2015

Journal of Surgical Research

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“…The increase of ALT and AST [20] was probably caused by the three-times higher dose of C used, compared to our study. Other authors have obtained results similar to those of Korolczuk et al [20][21][22][23][24][25]. It is worth noting that, in all of these experiments, the animals were exposed only to a single immunosuppressive drug, C.…”

Section: Discussionsupporting

confidence: 75%

Immunosuppressive treatment affects morphology and apoptotic intensity of the liver in pregnant Wistar rats

Szypulska-Koziarska¹,

Wilk²,

Kabat‐Koperska³

et al. 2018

jogi

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Introduction: Immunosuppressive drugs are crucial for patients who have undergone transplantation. These medicines prolong proper functioning of the transplanted organ, but, on the other hand, they lead to various disorders, including pathological alterations within native organs and apoptosis. The aim of our study was to investigate the influence of immunosuppressive drugs on morphology, physiology and hepatocyte apoptosis in the liver of pregnant female Wistar rats. Material and methods: The study was conducted on 32 female rats exposed to immunosuppressive drugs before (2 weeks) and during pregnancy (3 weeks). The regimens included drugs commonly used in therapy following kidney transplantation (cyclosporine A, mycophenolate mofetil, prednisone, tacrolimus and everolimus). Results: We observed a decreased liver weight in all treated dams in comparison to the control rats. No statistically significant differences among all examined groups were found regarding the concentration of either alanine or aspartate aminotransferase. The most pronounced apoptosis and the most severe morphological abnormalities were found in rats treated with cyclosporine A, prednisone and everolimus; but moderate changes were visible in other treatment groups. The alterations that we observed included dilated sinusoids, inflammation foci, the disappearance of boundaries between hepatocytes, ruptured blood vessels, degradation of cytoplasm, and hemosiderosis. Conclusions: It seems possible that the alterations seen here are due to the early stage of liver damage, and that the biochemical parameters of the liver were not affected yet. Immunosuppressive therapy during pregnancy disturbs the physiology of the liver, and causes morphological changes in this organ.

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Cyclosporine A-induced acute hepatotoxicity in guinea pigs is associated with endothelin-mediated decrease in local hepatic blood flow

Cited by 11 publications

References 33 publications

Oxidative Stress and Liver Morphology in Experimental Cyclosporine A-Induced Hepatotoxicity

Oxidative Stress and Liver Morphology in Experimental Cyclosporine A-Induced Hepatotoxicity

Effects of antioxidant agents against cyclosporine-induced hepatotoxicity

Immunosuppressive treatment affects morphology and apoptotic intensity of the liver in pregnant Wistar rats

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