Dietary Azithromycin Alters Detoxification Capacity and Induces Oxidative Damage in the Hemolymph of Galleria mellonella Larvae.

Understanding the biochemical impact of nontarget clinical drugs on insect models provides critical insights into xenobiotic toxicity. In this study, we investigated the biochemical effects of dietary AZR on the hemolymph of seventh-instar Galleria mellonella (Lepidoptera: Pyralidae) larvae. First-instar larvae of the insect were reared under laboratory conditions until the seventh-instar larvae. The larvae were fed an artificial diet supplemented with azithromycin (AZR) at different concentrations: 0.0012, 0.0072, 0.0432, 0.2592, 0.7776, and 1.0368%. Our results demonstrated that dietary AZR exposure significantly induced oxidative damage and impacted the defense system of the insect's hemolymph. At a low concentration of AZR (0.0072%), a statistically significant increase in MDA (from 0.065 ± 0.001 to 0.094 ± 0.002 nmol/mg protein) and PCO (from 327.462 ± 13.4 to 432.648 ± 41.17 nmol/mg protein) content was detected. The highest concentration of the antibiotic significantly increased CYP450 enzyme activity from 57.75 ± 5.61 to 113.1 ± 5.53 U/mg protein by about twofold. However, at this same concentration, GST activity decreased from 277.34 ± 15.13 to 172.34 ± 12.51 nmol/mg protein/min. Compared with the control, a statistically significant decrease in TP contents was observed in all treatment groups, except for the 0.0432% concentration. These findings suggest that dietary AZR triggers significant oxidative stress and disrupts the detoxification balance in G. mellonella hemolymph. Consequently, the current data demonstrate hemolymph biochemical stress responses to AZR exposure in G. mellonella.