Fullerenol nanoparticles prevents doxorubicin-induced acute hepatotoxicity in rats

Jacević, Vesna; Djordjević, Aleksandar; Srdjenović, Branislava; Milic-Tores, Vukosava; Šegrt, Zoran; Dragojević-Simić, Viktorija; Kuča, Kamil

doi:10.1016/j.yexmp.2017.03.005

Cited by 50 publications

(46 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was shown that the earliest and most frequent changes in the rat liver and kidney after application of DOX, in cumulative dose, were the consequences of its toxic effect on the hepatocyte, endothelial cells, and renal tubular epithelial cells [18,32,59]. The current understanding of molecular mechanisms underlying DOX-induced hepatic and renal cell type of death, both apoptosis and necrosis, implies excessive toxic and ischemic injuries of the hepatocytes, renal epithelial cells and vascular endothelium in the experimental animals [18,32,59,60], which was substantiated by our results. Chemotherapeutic agents may cause direct hepatic toxicity, and alteration of its function may affect drug metabolism and cause an increased risk of general toxicity [61].…”

Section: Discussionmentioning

confidence: 99%

“…An already weakened heart is unable to increase cardiac output, so further increase in the intravascular volume and venous pressure leads to additional fluid release into the tissues. On the other hand, hepatic oedema contributes to the increased permeability of the capillary wall that has already arisen due to the damage under the influence of DOX [9,15,32,59]. Such intensive disorders of water metabolism lead to the formation of small or large vacuoles in the cytoplasm of hepatocytes, as result of extreme enlargement of mitochondria and vesiculation of endoplasmic reticulum.…”

Section: Discussionmentioning

confidence: 99%

“…The severity of hepatic and renal lesions consisting of edema, cellular infiltration, hemorrhages, vacuolar degeneration, necrosis, and the distribution of lesions (e.g., focal, multifocal, locally extensive, or diffuse) were assessed and graded by two independent pathologists. From each slice, whole visual fields were analyzed by using light microscope according to the 5-point semiquantitative scale previously described [32,73]. A severity grade was expressed as hepatic damage score (HDS) and renal damage score (RDS), and the exact method of calculation is shown in Table 4 and Table 5, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…It is considered that the successful prevention or treatment of these DOX-induced harmful effects depends on antioxidative potential of different cytoprotective agents and their ability to react with highly reactive oxygen species (ROS) [12,13,26,28,29,30,31,32]. …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Efficacy of Amifostine against Multiple-Dose Doxorubicin-Induced Toxicity in Rats

Jaćević

Dragojević-Simić

Tatomirovic

et al. 2018

IJMS

View full text Add to dashboard Cite

Amifostine is well known cytoprotector which is efficient when administered before a wide range of antineoplastic agents. The aim of our study was to investigate amifostine effects on doxorubicin-induced toxic changes in rats. Amifostine (75 mg/kg ip) was given 30 min before each dose of doxorubicin (cumulatively 20 mg/kg ip, for 28 days). The animals’ whole-body, liver, and kidney weight, serum biochemical examination, as well as microscopic examination of bone marrow, peripheral blood, liver, and kidney, were done on day 56 of the study. Hepatic and renal alterations were carefully quantified by semiquantitative grading scales—hepatic and renal damage score, respectively. In amifostine-pretreated rats, the number of peripheral blood leukocytes was significantly higher in comparison to doxorubicin-only treated group, preferentially protecting neutrophils. In the same group of rats, hepatic and renal alterations associated with polymorphonuclear cell infiltrates were significantly less severe than those observed in animals receiving only doxorubicin. Our results showed that amifostine successfully protected rats against multiple-dose doxorubicin-induced toxicity by complex, and still not fully elucidated mechanisms of action.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Efficacy of Amifostine against Multiple-Dose Doxorubicin-Induced Toxicity in Rats

Jaćević

Dragojević-Simić

Tatomirovic

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…Fullerenes are commonly classified as "radical sponges" [2] due to their remarkable reactivity with free radicals [3][4][5][6]. The radical scavenging properties of fullerenes have found many applications in biological systems.…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Cheminformatics Analysis of Structural Features Affecting the Binding Activity of Fullerene Derivatives

et al. 2020

View full text Add to dashboard Cite

Nanostructures like fullerene derivatives (FDs) belong to a new family of nano-sized organic compounds. Fullerenes have found a widespread application in material science, pharmaceutical, biomedical, and medical fields. This fact caused the importance of the study of pharmacological as well as toxicological properties of this relatively new family of chemicals. In this work, a large set of 169 FDs and their binding activity to 1117 disease-related proteins was investigated. The structure-based descriptors widely used in drug design (so-called drug-like descriptors) were applied to understand cheminformatics characteristics related to the binding activity of fullerene nanostructures. Investigation of applied descriptors demonstrated that polarizability, topological diameter, and rotatable bonds play the most significant role in the binding activity of FDs. Various cheminformatics methods, including the counter propagation artificial neural network (CPANN) and Kohonen network as visualization tool, were applied. The results of this study can be applied to compose the priority list for testing in risk assessment related to the toxicological properties of FDs. The pharmacologist can filter the data from the heat map to view all possible side effects for selected FDs.

show abstract

Trehalose alleviates doxorubicin‐induced cardiotoxicity in female Swiss albino mice by suppression of oxidative stress and autophagy

Abu-Khudir

Ibrahim

Shams

et al. 2021

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Clinically, the use of doxorubicin (DOX) is limited due to DOX-induced cardiotoxicity (DIC). The current study aimed to evaluate the cardioprotective effect of trehalose (TRE) against DIC in a female Swiss albino mouse model. Mice were divided into five experimental groups: Gp. I: saline control group (200 μl/mouse saline three times per week for 3 weeks day after day), Gp. II: DOX-treated group (2 mg/kg body weight three times per week for 3 weeks day after day), Gp. III: TRE group (200 μg/mouse three times per week for 3 weeks day after day), Gp. IV: DOX + TRE cotreatment group (animals were coadministered with DOX and TRE as in Gp. II and III, respectively), and Gp. V: DOX + TRE posttreatment group (animals were treated with DOX as in Gp. II followed by treatment with TRE as in Gp. III). DOX-treated mice showed significant elevation in cardiac injury biomarkers (lactate dehydrogenase, creatine kinase isoenzyme-MB, and cardiac troponin I), cardiac oxidative stress (OS) markers (malondialdehyde and myeloperoxidase), and cardiac levels of autophagyrelated protein 5. Moreover, DOX significantly reduced the levels of total antioxidant capacity and activities of catalase and glutathione S-transferase.In contrast, TRE treatment of DOX-administered mice significantly improved almost all of the above-mentioned assessed parameters. Furthermore, histopathological changes of cardiac tissues observed in mice treated with TRE in combination with DOX were significantly improved as compared to DOXtreated animals. Taken together, the present study provides evidence that TRE has cardioprotective effects against DIC, which is likely mediated via suppression of OS and autophagy.

show abstract

Fullerenol nanoparticles prevents doxorubicin-induced acute hepatotoxicity in rats

Cited by 50 publications

References 45 publications

The Efficacy of Amifostine against Multiple-Dose Doxorubicin-Induced Toxicity in Rats

The Efficacy of Amifostine against Multiple-Dose Doxorubicin-Induced Toxicity in Rats

A Comprehensive Cheminformatics Analysis of Structural Features Affecting the Binding Activity of Fullerene Derivatives

Trehalose alleviates doxorubicin‐induced cardiotoxicity in female Swiss albino mice by suppression of oxidative stress and autophagy

Contact Info

Product

Resources

About