PLGA nanoparticles provide a safe delivery system for bee venom and melittin to alleviate their hepatotoxic effects...

Bee venom and its principal peptide, melittin, are natural compounds with many therapeutic effects. They are also known for their hemolytic and cytotoxic properties that render their medical applications. Poly lactic-co-glycolic acid (PLGA) is a popular polymer used for different drug delivery. The present study investigated the toxic effect of bee venom and melittin on the liver of mice. Furthermore, the impact of delivering bee venom and melittin via PLGA nanoparticles on reducing their toxic effects was investigated. Fifty male mice were divided randomly into five equal groups and were injected intra-peritoneally for 3 weeks as follows: control (saline), bee venom (15 μg/kg), melittin (500 μg/kg), bee venom loaded PLGA NPs (15 μg/kg), PEG targeted melittin-encapsulated PLGA-NPs (250 μg/kg). The hepatotoxic effect was examined through liver function tests (alanine aminotransferase, alkaline phosphatase), and oxidative stress was determined (total antioxidant capacity, malondialdehyde). Additionally, apoptosis (DNA fragmentation test, caspase3), inflammation (IL1β) and histopathological analysis were measured. The results revealed that melittin and bee venom have toxic effects on the liver, which were evidenced by increased liver enzymes and oxidative stress markers, in addition to inflammation and apoptosis caused by both substances. On the other hand, using the PLGA delivery system ameliorated most of these toxic effects. The present study proved that bee venom and melittin cause hepatotoxic effects and using the PLGA delivery system reduced most of these toxic effects enabling safer usage of melittin and bee venom in the future.