Lung and liver responses to 1- and 7-day treatments with LASSBio-596 in mice subchronically intoxicated by microcystin-LR

Abstract

Microcystin-LR (MC-LR) can cause serious injuries upon short- and long-term exposures that can be prevented by LASSBio-596 (LB-596), an anti-inflammatory compound. We aimed to test LB-596 following subchronic exposure to MC-LR. Swiss mice received 10 intraperitoneal injections of distilled water (DW) or MC-LR (20 μg/kg bw) every 2 days. On the 10th injection animals receiving DW were gavaged with DW or 50 mg/kg bw of LB-596 for 1 or 7 days (C1D, C7D, CL1D and CL7D groups), whereas those exposed to MC-LR received either DW or 50 mg/kg of LB-596 for 1 or 7 days (T1D, T7D, TL1D and TL7D groups). Twelve hours after the last gavage we assessed respiratory mechanics, and extracted lung and liver for histology, apoptosis, inflammatory biomarkers and MC-LR content. C1D, C7D, CL1D and CL7D were all similar. Mechanical parameters were significantly higher in T1D and T7D compared to the other groups. LB-596 reversed these changes on day 1 of administration. LB-596 reduced inflammatory mediators in lung and liver on day 1 of treatment. On day 7 apoptosis in liver and lung fell even more. Briefly, 7-day administration completely reversed lung and liver changes.

Keywords: Inflammation; LASSBio-596; Liver injury; Lung mechanics; Microcystin-LR; Subchronic exposure.