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Abstract:
A large, and increasing number of drugs and chemicals have been found which are toxic to lung following systemic administration. These agents damage lung tissue specifically, or in addition to damage to other tissues. Mechanisms explaining the pulmonary damage produced by some lung toxins have been uncovered. These include concentration of the agent within lung, the absence of adequate pulmonary detoxication systems, and bioactivation to a toxic species within specific lung cells or at distant sites followed by transport to the lung. The basic biochemical lesions underlying lung damage, responses of individual lung cells and pulmonary repair processes to the toxic agent, and species and age differences in susceptibility to lung damage have not, however, been well defined for most lung toxins. This review describes the information available on pulmonary biochemical and pathological changes associated with some of these lung-toxic agents. In addition, mechanisms proposed to explain the lung damage are discussed. The agents covered include: paraquat, the thioureas, butylated hydroxytoluene, the trialkylphosphorothioates, various lung-toxic furans and antineoplastic agents, the pyrrolizidine alkaloids, metals and organometallic compounds, amphiphilic agents, hydrocarbons, oleic acid, 3-methylindole, and diabetogenic agents. Detailed reviews on the overall toxicity of many of these agents have been published elsewhere. This review concentrates on their pulmonary toxicity. Information is presented as an overview to illustrate both the extensive literature that is available and the important questions that remain to be answered about systemic chemicals that damage lung tissue.
Insights
Many systemic drugs and chemicals can harm lung tissue. This review details known lung toxins, their mechanisms of action, and remaining questions about pulmonary toxicity.
Area of Science:
- Toxicology
- Pulmonary Medicine
- Biochemistry
Background:
- Systemic administration of drugs and chemicals can lead to lung toxicity.
- Specific mechanisms of pulmonary damage are increasingly understood, involving factors like agent concentration and bioactivation.
- However, fundamental biochemical lesions and cellular responses to most lung toxins remain poorly defined.
Purpose of the Study:
- To review available information on pulmonary biochemical and pathological changes caused by systemic lung toxins.
- To discuss proposed mechanisms underlying lung damage induced by these agents.
- To highlight knowledge gaps regarding the susceptibility and responses to lung toxins.
Main Methods:
- Literature review of systemic agents causing pulmonary toxicity.
- Analysis of biochemical and pathological changes associated with lung toxins.
- Discussion of proposed mechanisms of lung injury.
Main Results:
- Identified numerous agents causing lung toxicity, including paraquat, thioureas, furans, antineoplastics, and metals.
- Described mechanisms such as high lung concentration, impaired detoxification, and bioactivation.
- Highlighted species, age, and cellular differences in susceptibility and response.
Conclusions:
- Significant progress has been made in understanding lung toxins, but many questions remain unanswered.
- Further research is needed to define biochemical lesions, cellular responses, and repair processes.
- A comprehensive understanding of systemic chemical lung toxicity is crucial for prevention and treatment.