Acute peat smoke inhalation sensitizes rats to the postprandial cardiometabolic effects of a high fat oral load

Abstract

Wildland fire emissions cause adverse cardiopulmonary outcomes, yet controlled exposure studies to characterize health impacts of specific biomass sources have been complicated by the often latent effects of air pollution. The aim of this study was to determine if postprandial responses after a high fat challenge, long used clinically to predict cardiovascular risk, would unmask latent cardiometabolic responses in rats exposed to peat smoke, a key wildland fire air pollution source. Male Wistar Kyoto rats were exposed once (1 h) to filtered air (FA), or low (0.36 mg/m particulate matter) or high concentrations (3.30 mg/m) of peat smoke, generated by burning peat from an Irish bog. Rats were then fasted overnight, and then administered an oral gavage of a HF suspension (60 kcal% from fat), mimicking a HF meal, 24 h post-exposure. In one cohort, cardiac and superior mesenteric artery function were assessed using high frequency ultrasound 2 h post gavage. In a second cohort, circulating lipids and hormones, pulmonary and systemic inflammatory markers, and circulating monocyte phenotype using flow cytometry were assessed before or 2 or 6 h after gavage. HF gavage alone elicited increases in circulating lipids characteristic of postprandial responses to a HF meal. Few effects were evident after peat exposure in un-gavaged rats. By contrast, exposure to low or high peat caused several changes relative to FA-exposed rats 2 and 6 h post HF gavage including increased heart isovolumic relaxation time, decreased serum glucose and insulin, increased CD11 b/c-expressing blood monocytes, increased serum total cholesterol, alpha-1 acid glycoprotein, and alpha-2 macroglobulin (p = 0.063), decreased serum corticosterone, and increased lung gamma-glutamyl transferase. In summary, these findings demonstrate that a HF challenge reveals effects of air pollution that may otherwise be imperceptible, particularly at low exposure levels, and suggest exposure may sensitize the body to mild inflammatory triggers.

Cardiovascular health impacts of wildfire smoke exposure

“…Though minimal immune cell changes were observed in the bronchoalveolar lavage fluid (BALF), high doses of peat smoke PM extract (350 μg per animal) led to altered regulation of ventricular ejection and filling volumes, affecting blood flow in the pulmonary circulation [ 148 ]. In a study investigating the cardiometabolic responses to a high fat diet, rats exposed to peat fire smoke for 1 h showed increases in serum high-density lipoprotein (HDL) and total cholesterol, as well as increased isovolumic heart relaxation time after high fat food challenge, compared to values seen in control rats exposed to filtered air [ 93 ].…”

Lack of Acute Toxicity and Mutagenicity from Recombinant Epinephelus lanceolatus Piscidin Expressed in Pichia pastoris

“…In the oral toxicity study, we found that the acute oral LD 50 of rEP was greater than 5 g/kg body weight in female rats. This result shows that even a very high concentration did not cause notable toxicity in test animals [33]. In addition, no mortality or significant variations in body weight were observed.…”

“…Tests like oral toxicity, inhalation toxicity, eye irritation, and skin sensitization are commonly conducted to assess the safety of test molecules [31]. Acute oral toxicity is generally evaluated by oral gavage of rats [32][33][34]. Similarly, acute inhalation toxicity studies are performed by exposing rat models to liquid aerosols for a given period of time [32,33].…”

“…Acute oral toxicity is generally evaluated by oral gavage of rats [32][33][34]. Similarly, acute inhalation toxicity studies are performed by exposing rat models to liquid aerosols for a given period of time [32,33]. Another established method of toxicological assessment is to instill the drug into the lower conjunctiva of the left eye of rabbit models and assess irritation [35].…”

Alterations in CNS Functions and DNA Methylation in Rats after 24 h Exposure to Peat Smoke

“…Although air pollution from wildfire smoke is known to cause respiratory irritation and damage, its effect on the central nervous system is not well described. The problem of the adverse mental health effects caused by particulate matter is of particular relevance [13][14][15]. Current evidence links wood smoke exposure to cognitive dysfunction, including dementia and Alzheimer's disease [16].…”