Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories

Kim, Kyuri; Chini, Naseem; Fairchild, David G.; Engle, Steven K.; Reagan, William J.; Summers, Sandra; Mirsalis, Jon C.

doi:10.1177/0192623316668276

Cited by 22 publications

(13 citation statements)

References 60 publications

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“…It was also established by the observed histopathological alterations of cardiac tissues. CK and ANP are myocardium-specific protein reported as useful biomarkers for heart diseases [ 32 ]. Previous studies reported the increased release of CK and ANP from myocardial tissues with DOX treatment [ 33 – 35 ].…”

Section: Discussionmentioning

confidence: 99%

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Omega-3 fatty acids ameliorate doxorubicin-induced cardiorenal toxicity: In-vivo regulation of oxidative stress, apoptosis and renal Nox4, and in-vitro preservation of the cytotoxic efficacy

et al. 2020

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This study examines the protective effects of omega‐3 fatty acids (OMG), a frequently used nutritional therapy in cancer patients, against doxorubicin (DOX)‐induced acute cardiorenal toxicity in rats, and evaluates the cytotoxic activity of DOX when used with OMG against breast cancer cell line. Five groups of rats were treated for 4 consecutive weeks with vehicle (groups I & II), or OMG (25, 50 or 100 mg/kg/day, po; groups III, IV & V, respectively). After twenty-four hours, the last four groups were injected with DOX (200 mg/kg, ip). In DOX-treated rats, the altered ECG, serum cardiac and renal function biomarkers, and histopathological features indicated the induction of cardiorenal toxicity. Increased oxidative and apoptotic markers in both organs was observed, with elevated renal contents of NADPH-oxidase-4 (Nox4) and renin. OMG pretreatment improved those DOX-induced impairments in a dose-dependent manner, and showed antioxidant and antiapoptotic effects with regulation of renal Nox4 expression. The in-vitro study showed preservation of the cytotoxic activity of DOX on MCF7 cell line in the presence of OMG. The data suggests OMG for protection against acute DOX‐induced cardiorenal damage without affecting the latter antitumor activity. It proposes regulation of oxidative stress, Nox4 activity and apoptosis as contributing protective mechanisms.

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Section: Discussionmentioning

confidence: 99%

“…and ANP are myocardium-specific protein reported as useful biomarkers for heart diseases [32]. Previous studies reported the increased release of CK and ANP from myocardial tissues with DOX treatment [33][34][35].…”

Section: Plos Onementioning

confidence: 99%

Omega-3 fatty acids ameliorate doxorubicin-induced cardiorenal toxicity: In-vivo regulation of oxidative stress, apoptosis and renal Nox4, and in-vitro preservation of the cytotoxic efficacy

et al. 2020

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“…At the end of treatment, the animals were treated with the anesthetic agent and a 0.8 mL sample of the ventricular intracardiac blood was collected using a sterile microsyringe (1 mL) and an EDTA Vacutainer. The cardiac natriuretic peptides NT‐proANP and NT‐proBNP were evaluated using electrochemiluminescent assays, including the Rat Muscle Injury Panel 1 Assay, Rat NT‐proANP kit K153MBD, and Rat NT‐proBNP kit K153JKD from Meso Scale Discovery (MSD, Gaithersburg, MD) 49. The serum samples were diluted 1:4 and 50 μL of diluted sample (for Rat NT‐proANP and Rat NT‐proBNP) was dispensed and tested in duplicate according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

“…The cardiac natriuretic peptides NT-proANP and NT-proBNP were evaluated using electrochemiluminescent assays, including the Rat Muscle Injury Panel 1 Assay, Rat NT-proANP kit K153MBD, and Rat NT-proBNP kit K153JKD from Meso Scale Discovery (MSD, Gaithersburg, MD). 49 The serum samples were diluted 1:4 and 50 μL of diluted sample (for Rat NT-proANP and Rat NT-proBNP) was dispensed and tested in duplicate according to the manufacturer's protocol. After the completion of the procedure based on the MSD assay protocol, the plates were analyzed using an MSD Sector Imager, Model 2400.…”

Section: Serum Biochemistry and Electrochemistrymentioning

confidence: 99%

The hydroxypropyl‐β‐cyclodextrin‐minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats: Implications in the treatment of alopecia

Maqoud

Zizzo

Mele

et al. 2020

Pharmacology Res & Perspec

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The efficacy of minoxidil (MXD) ethanolic solutions (1%‐5% w/v) in the treatment of androgenetic alopecia is limited by adverse reactions. The toxicological effects of repeated topical applications of escalating dose (0.035%‐3.5% w/v) and of single and twice daily doses (3.5% w/v) of a novel hydroxypropyl‐β‐cyclodextrin MXD GEL formulation (MXD/HP‐β‐CD) and a MXD solution were investigated in male rats. The cardiovascular effects were evaluated by telemetric monitoring of ECG and arterial pressure in free‐moving rats. Ultrasonographic evaluation of cardiac morphology and function, and histopathological and biochemical analysis of the tissues, were performed. A pharmacovigilance investigation was undertaken using the EudraVigilance database for the evaluation of the potential cancer‐related effects of topical MXD. Following the application of repeated escalating doses of MXD solution, cardiac hypertrophy, hypotension, enhanced serum natriuretic peptides and K+‐ion levels, serum liver biomarkers, and histological lesions including renal cancer were observed. In addition, the administration of a twice daily dose of MXD solution, at SF rat vs human = 311, caused reductions in the systolic, diastolic, and mean blood pressure of the rats (−30.76 ± 3%, −28.84 ± 4%, and −30.66 ± 5%, respectively, vs the baseline; t test P < .05). These effects were not reversible following washout of the MXD solution. Retrospective investigation showed 32 cases of cancer associated with the use of topical MXD in humans. The rats treated with MXD HP‐β‐CD were less severely affected. MXD causes proliferative adverse effects. The MXD HP‐β‐CD inclusion complex reduces these adverse effects.

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“…4). Especially, NeuN and Myl3 (a selective marker for myocardial cells) (Kim et al, 2016) coexpressed at cytoplasm in myocardial cells, though NeuN expressed at a lower level (Fig. 5).…”

Section: Neun Expressed At Protein Level In Different Organs Assayed mentioning

confidence: 97%

A pilot study on searching for peri-nuclear NeuN-positive cells

Zhang

et al. 2020

PeerJ

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The aim of this study was to find out neuron (-like) cells in peripheral organs by cell markers in rats. Adult male Sprague-Dawley rats were anaesthetized. Their organs including brain, heart, lung, liver, kidney, stomach, duodenum, and ileum were harvested. The mRNA and protein in these organs were extracted. RNA sequencing (RNA-Seq) was carried out, and NeuN, a ''specific'' marker for neuronal soma, was assayed with Western blotting. The sections of the aforementioned organs were obtained after a routine fixation (4% methanal)-dehydration (ethanol)-embedding (paraffin) process. NeuN in the sections and seven non-neuronal cell lines was analyzed by immunofluorescence (IF) or immunohistochemistry (IHC). Neuronal markers, such as Eno2, NeuN (Rbfox3), choline acetyltransferase (Chat), as well as tyrosine hydroxylase (Th), and neuronal-glial markers, e.g., glial fibrillary acidic protein (Gfap), S100b, 2 , 3 -cyclic nucleotide 3 -phosphodiesterase (Cnp), and other related markers, were positively expressed in all the organs at mRNA level. NeuN was further analyzed by Western blotting. The IF and IHC assays showed that NeuN-positive cells were distributed in all the peripheral tissues (mainly peri-nuclear NeuN-positive cells) though with different patterns from that in brain (nuclear NeuN-positive cells), and a NeuN-negative tissue could not be found. Especially, NeuN and Myl3 co-expressed in the cytoplasm of myocardial cells, suggesting that NeuN could possess other functions than neuronal differentiation. Also, the protein was positively expressed in seven nonneuronal cell lines. Our findings suggested that NeuN-positive cells exist widely, and without identification of its distribution pattern, the specificity of NeuN for neurons could be limited. . Chiu IM, Von Hehn CA, Woolf CJ. 2012. Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology. Nature Neuroscience 15(8):CQ, Yin Q. 2016. Novel insights into NeuN: from neuronal marker to splicing regulator. Molecular Neurobiology 53(3):Chelly J. 1999. Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron 23(2):247-256 DOI 10.1016/S0896-6273(00)80777-1. Gascon E, Vutskits L, Kiss JZ. 2007. Polysialic acid-neural cell adhesion molecule in brain plasticity: from synapses to integration of new neurons. Brain Res Rev 56(1):101-118 DOI 10.1016/j.brainresrev.2007.05.014. Gulyas AI, Miettinen R, Jacobowitz DM, Freund TF. 1992. Calretinin is present in non-pyramidal cells of the rat hippocampus-I. A new type of neuron specifically associated with the mossy fibre system. Neuroscience 48(1):1-27 DOI 10.1016/0306-4522(92)90334-X. Hou XL, Chen Y, Yin H, Duan WG. 2015. Combination of fasudil and celecoxib promotes the recovery of injured spinal cord in rats better than celecoxib or fasudil Immunocytochemical analysis of valproic acid induced histone H3 and H4 acetylation during differentiation of rat adipose derived stem cells into neuron-like cells. Biotechnic and...

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Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories

Cited by 22 publications

References 60 publications

Omega-3 fatty acids ameliorate doxorubicin-induced cardiorenal toxicity: In-vivo regulation of oxidative stress, apoptosis and renal Nox4, and in-vitro preservation of the cytotoxic efficacy

Omega-3 fatty acids ameliorate doxorubicin-induced cardiorenal toxicity: In-vivo regulation of oxidative stress, apoptosis and renal Nox4, and in-vitro preservation of the cytotoxic efficacy

The hydroxypropyl‐β‐cyclodextrin‐minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats: Implications in the treatment of alopecia

A pilot study on searching for peri-nuclear NeuN-positive cells

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