Punica granatum peel extract modulates levofloxacin-induced oxidative stress and testicular damage in rats

Levofloxacin (LEV) is one of the Fluoroquinolones antibiotic groups, which are utilized in the therapy of numerous diseases, particularly in reproductive organs. Punica granatum peel is a waste byproduct rich in phytochemicals that are known for their different biological activities. The current research was designed to assess the capability of pomegranate peel extract (PGPE) in counteracting LEV-induced oxidative stress and testicular injury in rats. Rats groups were divided as follows: control, PGPE (500 mg/kg BW), LEV (300 mg/kg BW), and PGPE plus LEV. Rats were treated orally for two weeks daily. The chemical and nutritional content of Punica granatum peel (PGP) were investigated. GC/MS analysis showed the major phytochemical constituents in PGPE as gallic acid, ellagic acid, 4H-Pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl, and caffeic acid with DPPH, ABTS, and NO radical scavenging activity, as well as Fe³⁺- reducing antioxidant activity. Results revealed that LEV increased TBARS and H₂O₂ concentrations and LDH activity in rat testes significantly. While the activities of antioxidant enzymes, phosphatases, aminotransferases, and reduced glutathione content as well as protein levels, were significantly reduced. Worthy changes in testosterone, luteinizing, and follicle-stimulating hormone levels, as well as sperm characteristics, were also discovered. LEV was also found to trigger apoptosis, as evidenced by elevated p53 and caspase-3 levels and decreased Bcl2 levels. Furthermore, alterations in histological and immunohistochemical PCNA expression were observed in rat testes, confirming the biochemical findings. Furthermore, PGPE pretreatment of LEV-treated rats restored the majority of the tested parameters when compared to the LEV-treated group. In conclusion, pomegranate peel extract had a powerful modulating role against the adverse effects of levofloxacin in rat testes and represents a perspective of the utilization of food waste by-products.