Cardiac Safety Biomarkers for Toxicity Testing

Biomarkers have long been used as indicators of biological changes. In the context of drug development, they serve two key functions: predicting drug efficacy and detecting potential toxicity.

Cardiotoxicity is a significant reason for the failure of preclinical safety tests during the drug development process. Consequently, monitoring cardiac toxicity through biomarkers is a crucial component of drug development.

Cardiac Safety Biomarkers for Toxicity Testing

The biomarkers NT-proANP and NT-proBNP are cardiac hormones released when the heart muscle is stretched. They are part of the natriuretic peptides family and serve as cardiac biomarkers in both human studies and in animal studies (1-4).

In preclinical settings, they have been effectively utilized to identify cardiotoxicity (3). NT-proBNP and NT-proANP have proven to be valuable tools that enhance the early detection of cardiovascular injury during drug development (4). NT-proANP has also been measured to study Heart Failure with preserved Ejection Fraction (HFpEF) in a mouse model to probe preload-dependency (5). Furthermore, N-terminal pro-atrial natriuretic peptide (NT-proANP) was also quantified to assess left ventricular (LV) function in a rat model of cardiac arrest (CA) (6).

Biomedica provides reliable ELISA kits for the quantification of NT-proBNP and NT-proANP in samples from humans and rodents.

Rat NT-proBNP ELISA (cat. no. BI-1204R)

• Sample type: rat serum, plasma
• Sample volume: 10 µL/well
• Sensitivity: LOD 21 pg/ml
• Standard curve range: 0 – 3200 pg/ml (0 / 100 / 200 / 400 / 800 / 1600 / 3200 pg/ml)
• Assay time: 3.5 hours
• Protocol booklet click here – reference values provided

 

NT-proBNP ELISA (cat.no. SK-1204) – for human serum and plasma samples

• CE marked for IVD use in the EU
• Proficiency testing , saliva protocol
• Widely cited

 

NT-proANP ELISA (Cat. No. BI-20892)

Due to the high sequence homology of NT-proANP among species the assay has also been used in rodent (rat, mouse) rabbit, and dog samples.

• Sample types: Serum, plasma, urine, cell culture supernatant (human, rat, mouse, rabbit samples)
• Sample volume: 10 µL/well
• Sensitivity: LOD 0.05 nmol/l (= 0.64 ng/ml)
• Standard curve range: 0 – 10 nmol/l (= 0 – 127 ng/ml)
• Assay time: 3.5 hours
• Citations all , citations with use of rat/mouse samples
• Protocol Booklet click here

 

Literature

1. Circulating N-terminal pro-atrial natriuretic peptide is an independent predictor of left ventricular hypertrophy in the general population. The Tromsø Study. Schirmer H and Omland T. Eur Heart J. 1999; 20(10):755-63. doi: 10.1053/euhj.1998.1396. Erratum in: Eur Heart J 1999 Oct;20(19):1439. PMID: 10329067.
2.  Biomarkers for the diagnosis and management of heart failure. Castiglione V et al., Heart Fail Rev. 2022; 27(2):625-643. PMID: 33852110.
3.  Cardiac Hypertrophy Working Group of the Predictive Safety Testing Consortium. Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy. Dunn ME et al., Toxicol Pathol. 2017; 45(2):344-352. PMID: 27102652.
4.  Integrated approach to early detection of cardiovascular toxicity induced by a ghrelin receptor agonist. Stokes AH et al., Int J Toxicol. 2015; 34(2):151-61. PMID: 25722321.
5. Preload dependence in an animal model of mild heart failure with preserved ejection fraction (HFpEF). Jacobsen JCBet al., Acta Physiol (Oxf). 2024; 240(3):e14099. PMID: 38230889.
6. Post-cardiac arrest temporal evolution of left ventricular function in a rat model: speckle-tracking echocardiography and cardiac circulating biomarkers. De Giorgio Det al., Eur Heart J Imaging Methods Pract. 2024; 2(1):qyae006. doi: 10.1093/ehjimp/qyae006. PMID: 39045191.