Absorption and elimination of poisons before entering the systemic circulation

Enter the target site from the blood circulation

Toxin-increasing effect

Detoxification

Non-covalent binding: Non-polar interactions or non-covalent binding bonds have relatively low energy and are usually reversible

covalent binding

dehydrogenation reaction

electron transfer

enzymatic reaction

The effects of poisons on target molecules mainly include two mechanisms

target molecule dysfunction

Structural destruction of target molecules

neoantigen formation

DNA methylation is a natural modification of DNA

Abnormal DNA methylation and toxic effects of exogenous chemicals

Histones are a class of small basic proteins that bind to DNA in the chromosomes of eukaryotic cells and are an important component of nucleosomes.

Abnormal histone modifications and toxic effects of exogenous chemicals

When genes are activated and transcribed, chromatin decondenses and nucleosomes become open and loose structures, making it easier for transcription factors to access and bind to nucleosome DNA, thereby regulating gene transcription.

Abnormal chromatin remodeling and toxic effects of exogenous chemicals

refers to those that do not code for proteins

Abnormal expression of non-coding RNA and toxic effects of exogenous chemicals

molecular repair

cell repair

tissue repair

Repair obstacles

Repair disorders causing toxicity

Stressor—heat shock protein HSP—a variety of stressors can cause eggs white matter degeneration

The stressors are mainly free radicals, reactive oxygen species (ROS) or active Nitrogen (RNS)

ROS and RNS are important parts of the body's defense system

Various immune cells in the body can kill tumor cells

ROS and RNS are directly or indirectly involved in detoxification in vivo

ROS participates in the regulation of cell signaling and gene expression

ROs cause cell apoptosis through the following mechanisms

Cells and tissues adapt to hypoxic stress to induce angiogenesis, iron Metabolism and glucose metabolism-related gene expression to maintain cell proliferation and survive

Ca2, NO, and CO all play a role in hypoxic signal transduction. important role

The key molecule is hypoxia-inducible factor 1

Damage to the endoplasmic reticulum and increased synthesis of proteins requiring processing and packaging It causes endoplasmic reticulum stress and unfolded protein response (UPR); PERK pathway; IRE1 pathway; ATF6 pathway

Genotoxic carcinogens and mutagens

UV rays and radionuclides

most chemotherapeutic substances

Certain metabolites produced during normal life processes

The mitogen-activated protein kinase (MAPK) pathway is a major signaling One of the signal transmission pathways

Dysregulation of gene expression

Dysregulation of transient cell activity

ATP depletion

Intracellular Ca2 continues to increase

ROS and RNS excessively produce some poisons

Interrelationships among various elements of cellular homeostasis disorders and their consequences