High-throughput screening for drug-induced hepatotoxicity using Biochemical assays

One of the most frequent reasons for drug drop-off during preclinical and post-approval drug safety is drug-induced liver injury (DILI), and the incentive of obtaining predictive, reliable and scalable in vitro toxicology testing systems. The paper will examine how the incorporation of high-throughput screening (HTS) with biochemical monitoring has been used to determine the hepatotoxicity of drugs using human cell lines of liver origin. The sensitive biochemical markers were tested using a set of ten drugs, a combination of hepatotoxic and non-hepatotoxic chemicals, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), adenosine triphosphate (ATP), and glutathione (GSH). 

The results demonstrated that the hepatotoxins are capable of causing cellular toxicity by releasing the cellular enzymes (ALT, AST, and LDH) in a dose-dependent manner, severe depletion of ATP and GSH levels, DNA laddering formation and oxidative stress. ANOVA showed that toxic and non-toxic tested groups differed significantly (p < 0.05), yet the receiver operating characteristic (ROC) curves revealed a strong effect strength with the ALT and ATP using tests (AUC > 0.85). HTS platforms were 70 per cent quicker than hand procedures to conduct their assays and guaranteed the uniformity of method information, so it was a suitable decision to conduct their toxicity tests at the early stage of drug development.

The research is useful in describing the usefulness of HTS biochemical assays with their advantage as highly sensitive, sensitive, and inexpensive preclinical drug safety investigation techniques. Although the use of immortalised cell lines and restricted scope of a biomarker is associated with limitations, the data finds its substantiation in clinical hepatotoxic mechanisms and regulatory requirements. The paper advises greater use of technologies of HTS in the pharmaceutical pipeline and suggests a more the pattern of 3D liver models and approaches to multi-omics with the aim of making translation even more accurate.