Pharmacological characterization and nephroprotective potential of venoms from three egyptian scorpion species.

INTRODUCTION: Scorpion venoms are complex natural mixtures rich in bioactive molecules with emerging pharmacological relevance. Drug-induced kidney injury, particularly from chemotherapy agents like Taxol® (paclitaxel), remains a significant clinical challenge. This study investigates the molecular composition, enzymatic activities, and potential nephroprotective effects of venoms from three Egyptian scorpion species (Leiurus quinquestriatus, Buthacus leptochelys, and Scorpio maurus palmatus) against Taxol®-induced kidney injury. METHODS: Comprehensive molecular mass profiling of the three venoms was performed using liquid chromatography-mass spectrometry (LC-MS). Enzymatic characterization included assays for hyaluronidase, phospholipase A2 (PLA2), hemolytic, and antibacterial activities. The disulfide-bonded versus non-disulfide-bonded peptide (NDBP) ratios were also determined. To evaluate nephroprotective efficacy, the venoms were administered in an in vivo model of Taxol®-induced nephrotoxicity. Renal antioxidant defenses, oxidative stress markers, inflammatory responses, and histopathological architecture were assessed. RESULTS: LC-MS revealed hundreds of venom components within the 500-9,000 Da range, indicating a high diversity of low-molecular-weight peptides. All venoms exhibited notable hyaluronidase activity, whereas PLA2 activity varied markedly: absent in L. quinquestriatus, low in B. leptochelys, and pronounced in S. m. palmatus. Minor hemolytic activity was observed only in B. leptochelys, and all venoms demonstrated weak antibacterial effects. The ratio of disulfide-bonded to non-disulfide-bonded peptides ranged from 7.5% NDBPs in L. quinquestriatus to 48% in S. m. palmatus. Despite these biochemical differences, all three venoms significantly attenuated Taxol-induced nephrotoxicity, as evidenced by restored renal antioxidant defenses, suppressed oxidative stress and inflammatory responses, and improved renal histopathological architecture. DISCUSSION: The inverse correlation between PLA2 and hyaluronidase activities, coupled with striking differences in peptide composition, exemplifies a biochemical trade-off in venom resource allocation-highlighting how distinct molecular solutions evolve to meet similar ecological demands. From a pharmacological perspective, the comparable nephroprotective efficacy across species suggests that scorpion venoms contain bioactive constituents capable of modulating key molecular pathways involved in drug-induced renal injury. In a pharmacoepidemiologic context, these findings highlight the potential of venom-derived compounds as adjunctive or protective agents to mitigate chemotherapy-associated nephrotoxicity, supporting further investigation into their safety, efficacy, and translational applicability.