Differences in cardiovascular toxicities associated with cigarette smoking and snuff use revealed using novel zebrafish models

Abstract

Tobacco use is strongly associated with cardiovascular disease and the only avoidable risk factor associated with development of aortic aneurysm. While smoking is the most common form of tobacco use, snuff and other oral tobacco products are gaining popularity, but research on potentially toxic effects of oral tobacco use has not kept pace with the increase in its use. Here, we demonstrate that cigarette smoke and snuff extracts are highly toxic to developing zebrafish embryos. Exposure to such extracts led to a palette of toxic effects including early embryonic mortality, developmental delay, cerebral hemorrhages, defects in lymphatics development and ventricular function, and aneurysm development. Both cigarette smoke and snuff were more toxic than pure nicotine, indicating that other compounds in these products are also associated with toxicity. While some toxicities were found following exposure to both types of tobacco product, other toxicities, including developmental delay and aneurysm development, were specifically observed in the snuff extract group, whereas cerebral hemorrhages were only found in the group exposed to cigarette smoke extract. These findings deepen our understanding of the pathogenic effects of cigarette smoking and snuff use on the cardiovascular system and illustrate the benefits of using zebrafish to study mechanisms involved in aneurysm development.

Zebrafish as a Vertebrate Model System to Evaluate Effects of Environmental Toxicants on Cardiac Development and Function

“…Exposure to the cigarette smoke condensates of all brands from 24–48 hpf with heartbeat measurement at 48 hpf showed reduction of embryo’s heartbeat by 50% [2]. Jensen and colleagues compared the toxicity of cigarette smoke and snuff extracts by continuously exposing 48 hpf embryos to either cigarette smoke extract or snuff extract for 24 h. Assessment of cardiac functions at 72 hpf revealed that exposure to both mixtures led to the reduction of both systolic and diastolic volumes, decrease in heart rate, stroke volume, and cardiac output [90]. …”

Zebrafish as a High-Throughput In Vivo Model for Testing the Bioactivity of Cannabinoids

“…Zebrafish larvae are an established model for testing vertebrate toxicity, teratogenicity and environmental risk assessment [120][121][122]. The use of these models has proven to be a valuable resource for testing the toxicity of various extracts and condensates obtained from tobacco cigarette smoke [6,123,124]. It was found that smoke from tobacco cigarettes was more toxic and produced different phenotypes than that of nicotine alone, suggesting, that the other toxic components found in tobacco smoke are having an effect.…”

Experiment and Animal Models of AAA

“…Another animal that was used as an angiotensin-induced aneurysm model was the zebrafish. This is primarily due to similar vasculogenesis with humans [42]. This model was used primarily to investigate the effects of smoking tobacco.…”