Effects of antioxidant agents against cyclosporine-induced hepatotoxicity

Akbulut, Sami; Elbe, Hülya; Eris, Cengiz; Doğan, Zümrüt; Toprak, Gülten; Yalcin, Erhan; Otan, Emrah; Türköz, Yusuf

doi:10.1016/j.jss.2014.08.042

Cited by 20 publications

(18 citation statements)

References 26 publications

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“…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%

“…The essential adverse effect of CsA is nephrotoxicity, yet there are also reports describing damage to other organs or systems, such as the heart, central nervous system, and testicles [ 6 , 18 – 21 ]. Moreover, clinical and experimental studies have demonstrated impaired liver function and morphology [ 10 – 12 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…The morphological changes observed in experimental animals receiving CsA include impaired trabecular structure, hepatic sinus congestion and widening, activation of the Kupffer cells, passive congestion and oedema of portal tracts, mild mononuclear cell infiltrations within portal tracts, and degenerative changes in the hepatocytes including their focal necrosis [ 10 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…The mechanisms of CsA-induced liver injury involve the development of hypermetabolic state in the liver [ 13 ] and inhibition of ATP-dependent transport of bilirubin and bile salts through the hepatocyte canalicular membranes as well as of bile secretion [ 14 , 15 ]. The use of antioxidants in experimental animals exposed to CsA reduces liver functional and morphological damage [ 11 , 12 , 16 , 17 ], which suggests the involvement of oxidative stress as one of the mechanisms of hepatotoxicity.…”

Section: Introductionmentioning

confidence: 99%

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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: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Korolczuk

Caban

Amarowicz

et al. 2016

BioMed Research International

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“…6). This is in agreement with previous reports that antioxidants may have a beneficial role in mitigating CsA-induced liver injury (307,308).…”

Section: Clinical Patterns and Mechanisms Of Drug-induced Liver Injursupporting

confidence: 94%

Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent

Parmentier¹,

Hendriks

Heyd

et al. 2018

Toxicology Letters

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A review: Systematic research approach on toxicity model of liver and kidney in laboratory animals

Abbasnezhad

Salami

Mohebbati

2022

Anim Models and Exp Med

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Therapeutic experiments are commonly performed on laboratory animals to investigate the possible mechanism(s) of action of toxic agents as well as drugs or substances under consideration. The use of toxins in laboratory animal models, including rats, is intended to cause toxicity. This study aimed to investigate different models of hepatotoxicity and nephrotoxicity in laboratory animals to help researchers advance their research goals. The current narrative review used databases such as Medline, Web of Science, Scopus, and Embase and appropriate keywords until June 2021. Nephrotoxicity and hepatotoxicity models derived from some toxic agents such as cisplatin, acetaminophen, doxorubicin, some anticancer drugs, and other materials through various signaling pathways are investigated. To understand the models of renal or hepatotoxicity in laboratory animals, we have provided a list of toxic agents and their toxicity procedures in this review.

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Effects of antioxidant agents against cyclosporine-induced hepatotoxicity

Cited by 20 publications

References 26 publications

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

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

Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent

A review: Systematic research approach on toxicity model of liver and kidney in laboratory animals

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