Acute cylindrospermopsin exposure: Pulmonary and liver harm and mitigation by dexamethasone

Abstract

Cylindrospermopsin (CYN) is a cyanotoxin of increasing worldwide environmental importance as it can harm human beings. Dexamethasone is a steroidal anti-inflammatory agent. Thus, we aimed at evaluating the pulmonary outcomes of acute CYN intoxication and their putative mitigation by dexamethasone. Male BALB/c mice received intratracheally a single dose of saline or CYN (140 μg/kg). Eighteen hours after exposure, mice instilled with either saline solution (Ctrl) or CYN were intramuscularly treated with saline (Tox) or 2 mg/kg dexamethasone (Tox + dexa) every 6 h for 48 h. Pulmonary mechanics was evaluated 66 h after instillation using the forced oscillation technique (flexiVent) to determine airway resistance (R_N), tissue viscance (G) and elastance (H). After euthanasia, the lungs were removed and separated for quantification of CYN, myeloperoxidase activity and IL-6 and IL-17 levels plus histological analysis. CYN was also measured in the liver. CYN increased G and H, alveolar collapse, PMN cells infiltration, elastic and collagen fibers, activated macrophages, peroxidase activity in lung and hepatic tissues, as well as IL-6 and IL-17 levels in the lung. Tox + Dexa mice presented total or partial reversion of the aforementioned alterations. Briefly, CYN impaired pulmonary and hepatic characteristics that were mitigated by dexamethasone.

Keywords: Cyanobacteria; Cylindrospermopsin; Dexamethasone; Inflammation; Lung.