Multiplex Toxicity Assays: Gain a Better Understanding of Toxicity Biomarkers
Section Overview
Toxicity affects all facets of biological research and drug development. A guiding tenet in toxicity studies is to eliminate toxic compounds as early as possible in the drug development process. Organ-specific toxicity testing is of chief importance because drug-induced toxicities in various organs are the leading cause of drug failure. Multiplex toxicity assays enable researchers to simultaneously measure multiple toxicity biomarkers for various organs to gain a better understanding of drug-induced toxicity. Learn how MILLIPLEX® multiplex toxicity assays are advancing research on liver injury, kidney toxicity, and more.
What Are Ideal Toxicity Biomarkers?
The ideal toxicity biomarkers are not only organ- or tissue-specific but are also sensitive enough to identify organ or tissue damage before it becomes too extensive. The Predictive Safety Testing Consortium (PSTC) identified and qualified several protein biomarkers that may better predict organ-specific toxicity, and regulatory agencies have recommended assay characteristics for establishing toxicity. Furthermore, toxicity biomarkers should ideally apply to preclinical models in which early safety is frequently assessed.
In addition to regulatory requirements in drug development, endocrine disruptor chemical (EDC) testing has been mandated by environmental regulatory agencies worldwide. New chemical entities, and even older pesticides, environmental chemicals, and food additives, are required to be tested for their capacity to disrupt human and animal developmental and reproductive health.
Examples of Toxicity Biomarkers
- Kidney Toxicity: KIM-1, Trefoil Factor 3 (TFF-3), Osteopontin, Clusterin, β2-Microglobulin, Renin, Calbindin, Cystatin C, Albumin
- Liver Injury: ARG1, GSTα, 5’-NT, GOT1, SDH
- Vascular Injury: Caveolin-1, MCP-1, TNF-α, CINC-1/GRO/KC, PAI-1, VEGF, IL-6, TIMP-1
- EDC: Cortisol, Testosterone, TSH, Estradiol, T3, T4, Progesterone
- Genotoxicity: Chk1, Chk2, H2A.X, p53, ATR, MDM2, p21
Multiplex Toxicity Assays
Bead-based multiplex toxicity assays enable a precise, multiparametric analysis of toxicity and its underlying processes. MILLIPLEX® multiplex toxicity biomarker assay kits enable researchers to simultaneously quantify dozens of toxicity analytes across several species (including rat, mouse, porcine, canine, and feline models). For example, these assays can analyze specific toxicities including:
- Drug-induced liver injury
- Kidney toxicity
- Genotoxicity
- Toxicity profiles in agrochemicals
- Early-stage toxicity testing evaluating effects of compounds on cell signaling pathways
Based on Luminex® xMAP® technology, our analytically verified assay kits provide:
- Standards verified to match reference lots
- Serum matrix for generating standard curves that accurately simulate conditions of native analyte conditions in serum or plasma
- In-assay controls
- Detection antibody cocktails to ensure consistent performance regardless of plex size
- A way to save precious sample. Determine how much sample is needed using Table 1.
Model | Mouse | Rat | Porcine (minipig) | Canine (beagle) |
|---|---|---|---|---|
Assumptions | 30 g body weight | 250 g body weight | 7.5 kg body weight | 9 kg body weight |
10/sex/group | 10/sex/group | 4/sex/group | 4/sex/group | |
4 groups | 4 groups | 4 groups | 4 groups | |
25, 250, and 500 mg/kg/day | 25, 250, and 500 mg/kg/day | 25, 250, and 500 mg/kg/day | 25, 250, and 500 mg/kg/day | |
28-day treatment | 28-day treatment | 28-day treatment | 28-day treatment | |
+20% extra | +20% extra | +20% extra | +20% extra | |
Test material required | ~62 g drug | ~520 g drug | ~3,120 g drug | ~7,500 g drug |
Related Products
Explore our popular MILLIPLEX® multiplex toxicity assays below.
Kidney Toxicity
Detecting qualified kidney toxicity biomarkers, in contrast to traditional BUN and serum creatinine (SCr) tests, can enable early detection and localization of kidney damage, which are crucial for the accurate assessment of toxicity.
Liver Injury
Biomarkers like ARG1 and SDH are hepatocellular and hepatobiliary enzymes that are released into circulation upon the occurrence of liver injury.
Vascular Injury
In addition to heart rate and mean arterial blood pressure, measuring key proteins in smooth muscle, endothelial cells, and immune-mediated cells may yield promising biomarkers for vascular injury.
Endocrine Disruptor Chemicals (EDC)
Reproductive, adrenal, thyroid, and pituitary hormone levels and their functions in humans and animals can be altered with exposure to EDCs. In vitro cell assays and in vivo models for various species may be used to assess the effects of chemical exposure.
Genotoxicity
Genotoxicity assays help researchers assess the effects of DNA damage.
For Research Use Only. Not For Use In Diagnostic Procedures.
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