Biomarker panel of cardiac and skeletal muscle troponins, fatty acid binding protein 3 and myosin light chain 3 for the accurate diagnosis of cardiotoxicity and musculoskeletal toxicity in rats

Tonomura, Yutaka; Matsushima, Shuuichi; Kashiwagi, Emi; Fujisawa, Kae; Takagi, Shingo; Nishimura, Yoko; Fukushima, Ryou; Torii, Mikinori; Matsubara, Mitsunobu

doi:10.1016/j.tox.2012.07.012

Cited by 55 publications

(44 citation statements)

References 43 publications

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“…In contrast, plasma AST, FABP3, Myl3 and miR-133a were drastically elevated after TMPD treatment and the extent of the change was similar in both techniques. The large signalto-noise ratios seen with these biomarkers regardless of sampling technique indicate their diagnostic accuracy in line with the previous work (Pritt et al, 2008;Tonomura et al, 2009;Tonomura et al, 2012;Laterza et al, 2009). The kinetics of these biomarkers were somewhat different; plasma CK-MM and FABP3 were drastically elevated 7 hr after the TMPD treatment, whereas plasma AST, Myl3 and miR-133 reached maximum at 24 hr after the TMPD treatment.…”

Section: Discussionsupporting

confidence: 84%

“…Thus, it is critical that investigators should consider the kinetics of each biomarker response to various types of compounds depending on their mode of action when interpreting results of the studies. Overall, combinational measurement of these biomarkers could supply useful information for detecting potential toxicity and target tissues for new chemical entities in nonclinical toxicological studies as several authors pointed out (Pritt et al, 2008;Tonomura et al, 2009;Tonomura et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, fatty acid binding protein 3 (FABP3) and myosin light chain 3 (Myl3) have been introduced into the toxicological field as promising biomarkers for skeletal myopathy (Pritt et al, 2008;Tonomura et al, 2009Tonomura et al, , 2012. Additionally, muscle specific microRNAs (e.g., miR-133a) have also been suggested as useful and reliable biomarkers for skeletal muscle injury in experimental animals (Laterza et al, 2009;Mizuno et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Impact of different blood sampling techniques on plasma biomarkers for skeletal myopathy in conscious rats

Miwa

Tamai

Kinpara

et al. 2015

Fundam. Toxicol. Sci.

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-To characterize variability of various musculoskeletal biomarkers by different blood sampling techniques in conscious rats, plasma asparate aminotransferase (AST), creatine kinase (CK) and its isoenzymes, fatty acid binding protein 3 (FABP3), myosin light chain 3 (Myl3) and microRNA (miR-133a) obtained by jugular venipuncture (C-JV) or tail venipuncture (C-TV) were compared with those obtained by jugular venipuncture (A-JV) in isoflurane-anesthetized rats. Plasma CK, FABP3 and Myl3, especially when collected by C-TV, were higher with larger variability than when collected by A-JV, whereas miR-133a displayed large variability in all techniques. Interestingly, higher CK obtained by C-JV or C-TV was largely attributable to higher CK-MM or CK-BB, respectively. Handling and restraint stress were identified as possible factors contributing to larger variability for CK, FABP3 and Myl3. A close correlation between CK and FABP3 was demonstrated both in the C-JV and C-TV techniques. Next, we evaluated the impact of C-JV and C-TV techniques for detecting skeletal myopathy in 2,3,5,6-tetramethyl-p-phenylenediamine-treated rats. In this model, CK and CK-MM obtained by C-TV were significantly increased, but those obtained by C-JV were not modified. In contrast, AST, FABP3, Myl3 and miR-133a obtained by both techniques were drastically elevated to a similar extent. The results suggest that, in conscious rats, the tail venipuncture technique may be more appropriate to detect skeletal myopathy despite the higher variability with this technique than with the jugular venipuncture technique. Furthermore, FABP3, Myl3 and miR-133a may serve as more sensitive biomarkers with large signal-to-noise ratios regardless of the blood sampling technique in conscious rats.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impact of different blood sampling techniques on plasma biomarkers for skeletal myopathy in conscious rats

Miwa

Tamai

Kinpara

et al. 2015

Fundam. Toxicol. Sci.

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“…Troponins I and T, FABP3, MYL3, and CK-MB were analyzed as specific biomarkers of cardiac damage. 23 No significant changes in troponins I and T, MYL3, or CK-MB were detected following KCN challenge in adult or juvenile mice. A significant increase in FABP3 was observed in the first 0.5 to 2 hours post-KCN challenge in adult mice ( Figure 14).…”

Section: Biomarkers and Histopathology Studymentioning

confidence: 91%

Characterization of a Mouse Model of Oral Potassium Cyanide Intoxication

et al. 2016

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Potassium cyanide (KCN) is an inhibitor of cytochrome C oxidase causing rapid death due to hypoxia. A well-characterized model of oral KCN intoxication is needed to test new therapeutics under the Food and Drug Administration Animal Rule. Clinical signs, plasma pH and lactate concentrations, biomarkers, histopathology, and cyanide and thiocyanate toxicokinetics were used to characterize the pathology of KCN intoxication in adult and juvenile mice. The acute oral LD50s were determined to be 11.8, 11.0, 10.9, and 9.9 mg/kg in water for adult male, adult female, juvenile male, and juvenile female mice, respectively. The time to death was rapid and dose dependent; juvenile mice had a shorter mean time to death. Juvenile mice displayed a more rapid onset and higher incidence of seizures. The time to observance of respiratory signs and prostration was rapid, but mice surviving beyond 2 hours generally recovered fully within 8 hours. At doses up to the LD50, there were no gross necropsy or microscopic findings clearly attributed to administration of KCN in juvenile or adult CD-1 mice from 24 hours to 28 days post-KCN challenge. Toxicokinetic analysis indicated rapid uptake, metabolism, and clearance of plasma cyanide. Potassium cyanide caused a rapid, dose-related decrease in blood pH and increase in serum lactate concentration. An increase in fatty acid-binding protein 3 was observed at 11.5 mg/kg KCN in adult but not in juvenile mice. These studies provide a characterization of KCN intoxication in adult and juvenile mice that can be used to screen or conduct preclinical efficacy studies of potential countermeasures.

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“…Mice were either fed (for cardiomyocyte injury measurement by plasma cardiac troponin I (cTnI), fatty acid binding protein 3 (FABP3) and myosin light chain 3 (Myl3) [30]) or fasted for 16 h (for glucose, triglyceride and insulin measurements) and anesthetized with isoflurane for facial vein puncture. Glucose and insulin tolerance tests (GTT and ITT) were performed as previously described [31].…”

Section: Methodsmentioning

confidence: 99%

Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy

Thoonen

Ernande

Cheng

et al. 2015

Journal of Molecular and Cellular Cardiology

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Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1 −/− ) mice, which have dysfunctional BAT, were subjected to catecholamineinduced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1 −/− mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1 −/− mice. UCP1 −/− mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1 −/− mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1 −/− BAT transplanted to either UCP1 −/− or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1 −/− mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1 −/− mice,

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Biomarker panel of cardiac and skeletal muscle troponins, fatty acid binding protein 3 and myosin light chain 3 for the accurate diagnosis of cardiotoxicity and musculoskeletal toxicity in rats

Cited by 55 publications

References 43 publications

Impact of different blood sampling techniques on plasma biomarkers for skeletal myopathy in conscious rats

Impact of different blood sampling techniques on plasma biomarkers for skeletal myopathy in conscious rats

Characterization of a Mouse Model of Oral Potassium Cyanide Intoxication

Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy

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