Multi-generational effects of enrofloxacin on lifespan and reproduction of Caenorhabditis elegans with SKN-1-mediated antioxidant responses and lipid metabolism disturbances.

Antibiotics are ubiquitous environmental pollutants and they can provoke multi-generational impacts due to their pseudo-persistence. However, their multi-generational effects and potential mechanisms remained poorly studied. Presently, effects of enrofloxacin (ENR) were studied on Caenorhabditis elegans with a continuous exposure over 9 generations (from F1 to F9) at an environmentally realistic level. Regarding reproduction, ENR showed stimulation in F1 (1.18-fold of the control) and F2 (1.08), inhibition in F3 (0.70), stimulation in F4 (1.86), F5 (3.18) and F6 (1.53), inhibition in F7 (0.73) and F8 (0.69) and stimulation again in F9 (1.89). That is to say, ENR provoked multi-generational oscillatory effects on the reproduction. Such oscillation was also observed in effects on lifespan with much less magnitudes than those on reproduction. Biochemical assays were performed in F1, F3, F4 and F9 which represented the oscillation over generations. Results showed more antioxidants (e.g., superoxide dismutase and glutathione), mild oxidative stress (e.g., reactive oxygen species) and less oxidative damage (i.e., protein carbonyl) underlying the generation-dependent stimulation. Moreover, ENR provoked multi-generational oscillation on the enzymes that regulate the lipogenesis (e.g., fatty acid synthase and acetyl-CoA carboxylase) and lipolysis (e.g., acyl-CoA synthetase), with similarities to the effects on the oxidative stress and damage. Further analysis on SKN-1 and its activating PMK-1 and GSK-3 demonstrated their involvement in regulating both antioxidant detoxification and lipid metabolism.