Subacute and sublethal ingestion of microcystin-LR impairs lung mitochondrial function by an oligomycin-like effect.

Microcystin-LR (MC-LR) is a potent cyanotoxin that can reach several organs. However subacute exposure to sublethal doses of MC-LR has not yet well been studied. Herein, we evaluated the outcomes of subacute and sublethal MC-LR exposure on lungs. Male BALB/c mice were exposed to MC-LR by gavage (30 µg/kg) for 20 consecutive days, whereas CTRL mice received filtered water. Respiratory mechanics was not altered in MC-LR group, but histopathology disclosed increased collagen deposition, immunological cell infiltration, and higher percentage of collapsed alveoli. Mitochondrial function was extensively affected in MC-LR animals. Additionally, a direct in vitro titration of MC-LR revealed impaired mitochondrial function. In conclusion, MC-LR presented an intense deleterious effect on lung mitochondrial function and histology. Furthermore, MC-LR seems to exert an oligomycin-like effect in lung mitochondria. This study opens new perspectives for the understanding of the putative pulmonary initial mechanisms of damage resulting from oral MC-LR intoxication.

The role of dual oxidases in physiology and cancer.

NOX/DUOX enzymes are transmembrane proteins that carry electrons through biological membranes generating reactive oxygen species. The NOX family is composed of seven members, which are NOX1 to NOX5 and DUOX1 and 2. DUOX enzymes were initially called thyroid oxidases, based on their high expression level in the thyroid tissue. However, DUOX expression has been documented in several extrathyroid tissues, mostly at the apical membrane of the salivary glands, the airways, and the intestinal tract, revealing additional cellular functions associated with DUOX-related H2O2 generation. In this review, we will briefly summarize the current knowledge regarding DUOX structure and physiological functions, as well as their possible role in cancer biology.