Sains Malaysiana 55(6)(2026): 998-1008

http://doi.org.10.17576/jsm-2026-5506-05

 

Integrative Systems Toxicology Shows Mechanisms of Food Additive-Induced Toxicity

(Toksikologi Sistem Integratif Menunjukkan Mekanisme Ketoksikan yang Disebabkan oleh Bahan Tambahan Makanan)

 

JING WANG* & LING MENG

 

College of Medicine Engineering, Lianyungang Technical College, Jiangsu, 222005, P.R. China

 

Diserahkan: 13 Januari 2026/Diterima: 25 Mei 2026

 

Abstract

Traditional single-target toxicity evaluation methods are insufficient to elucidate the individual and combined toxicities of food additives, primarily due to the diverse chemical structures of these additives and their multi-system biological targets. To address this limitation, the present study establishes a systematic toxicology framework that integrates oral bioavailability (OB), protein interaction prediction, network analysis, molecular docking, and pathway analysis. Our results showed 52 food additives exhibit significant potential toxicological effects. Network analysis identified 868 receptor proteins and 7 major disease categories via food additive-protein and protein-disease networks, indicating multi-target synergistic pathogenic effects. Key target proteins showed strong binding affinity with additives. Integrated GO/KEGG analyses showed three core toxicity mechanisms: dysregulated xenobiotic detoxification, abnormal chemical synaptic transmission, and amplified inflammatory signaling. These mechanisms are mediated by disrupted enzyme/receptor binding and perturbations in plasma membrane, synaptic, and cytosolic compartments, and are involved in neuroactive ligand-receptor interaction, cancer-related pathways, and HIF-1 signaling. This research provides comprehensive evidence for food additive safety evaluation and a novel paradigm for related studies.

Keywords: Food additive toxicity; molecular mechanism; systems toxicology

 

Abstrak

Kaedah tradisi penilaian ketoksikan sasaran tunggal tidak berupaya untuk menjelaskan ketoksikan individu dan gabungan bahan tambahan makanan, terutamanya disebabkan oleh struktur kimia yang pelbagai bagi bahan tambahan ini dan sasaran biologi berbilang sistemnya. Untuk menangani keterbatasan ini, kajian ini mewujudkan rangka kerja toksikologi sistematik yang mengintegrasikan bioketersediaan oral (OB), ramalan interaksi protein, analisis rangkaian, dok molekul dan analisis laluan. Keputusan kami menunjukkan 52 bahan tambahan makanan mempamerkan potensi kesan toksikologi yang ketara. Analisis rangkaian mengenal pasti 868 protein reseptor dan 7 kategori penyakit utama melalui rangkaian bahan tambahan-protein dan protein-penyakit makanan yang menunjukkan kesan patogen sinergi berbilang sasaran. Protein sasaran utama menunjukkan afiniti pengikatan yang kuat dengan bahan tambahan. Analisis GO/KEGG bersepadu mendedahkan tiga mekanisme ketoksikan teras: detoksifikasi xenobiotik yang tidak terkawal, penghantaran sinaptik kimia yang tidak normal dan isyarat keradangan yang diperkuat. Mekanisme ini dimediasi oleh pengikatan enzim/reseptor yang terganggu dan gangguan dalam membran plasma, petak sinaptik dan sitosolik dan terlibat dalam interaksi ligan-reseptor neuroaktif, laluan berkaitan kanser dan isyarat HIF-1. Penyelidikan ini menyediakan bukti komprehensif untuk penilaian keselamatan bahan tambahan makanan dan paradigma baharu untuk kajian berkaitan.

Kata kunci: Ketoksikan bahan tambahan makanan; mekanisme molekul; toksikologi sistem

 

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