LASSBio 596 improves function, inflammation and apoptosis in lung and liver of mice intoxicated with microcystin-LR

Rationale: Subchronic exposure to microcystin-LR (MCLR) may be more important than acknowledged. LASSBio 596 (LB596) reverses lung and liver injuries after acute exposure to MCLR. Aim: Test the therapeutic potential of LB596 after prolonged exposure to MCLR in mice. Methods: Our Institutional Ethics Board on Animal Use approved the study (code IBCCF162). Male Swiss mice received 10 intraperitoneal injections of distilled water (DW, 60 µL) or MCLR (20 µg/kg in DW, 60 µL) every other day. On the 10th injection animals receiving DW were gavaged with DW or 10 mg/kg of LB596 for 1 or 7 days (C1D, C7D CL1D and CL7D groups), whereas those exposed to MCLR received either DW or 10 mg/kg of LB596 for 1 or 7 days (T1D, T7D, TL1D and TL7D groups). 12 h after the last gavage lung mechanics, seric levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), apoptosis, and inflammation in livers and lungs were determined. General linear model followed by Mann-Whitney non-parametric U-test was used (α=5%). Results: C1D, C7D, CL1D and CL7D were similar and grouped as CTRL. Elastance (Est) was significantly higher in T1D (38.8±3.2 cmH 2 O/mL) and T7D (33.4±1.5 cmH 2 O/mL) than in CTRL, TL1D and TL7D (27.2±1.6, 25.4±1.7 and 27.5±1.6 cmH 2 O/mL, respectively). LB596 reversed these changes on the 1st day of administration. Pulmonary resistive and viscoelastic pressures followed Est. LB596 reduced inflammatory cytokines on the 1st day of treatment in lung and liver, but at the 7th day serum levels of ALT and apoptosis in liver and lung fell even more. Conclusion: 7-day administration completely reversed lung and liver changes. Supported by: FAPERJ, CAPES, CNPq, MCT, FINEP.