Time-Course physiopathology of Porthidium lansbergii lansbergii Envenomation in Swiss Webster Mice: Insights into Systemic Manifestations.

Abstract

Objective: The expansion of human activities in northern Colombia has increased human-snake encounters, particularly with venomous Porthidium lansbergii lansbergii. Given the limited knowledge of systemic envenomation effects and previous studies focusing only on early murine symptoms, this investigation aimed to describe the time-course physiopathology of P. lansbergii lansbergii envenomation following intramuscular injection in vivo.

Methods: Venom was inoculated in the gastrocnemius muscles of Swiss Webster mice, and blood, urine, and tissue samples were taken at different times to evaluate lethality and biochemical markers of renal function and oxidative stress.

Results: This study reports the first intramuscular LD₅₀ for P. lansbergii lansbergii venom at 24.83 mg/Kg. Administering 80% of this LD₅₀ induced early signs of renal injury, evidenced by urinary biomarkers over 24 h. The antioxidant activity was found at low levels in kidney tissue throughout the evaluated time post-envenomation. Malondialdehyde activity increased at the earliest point, while proinflammatory activity increased later. Urine metabolomics revealed elevated taurine and allantoin in the envenomed groups.

Discussion: Compensatory mechanisms in response to oxidative stress and tissue damage induced by the venom were evident in the envenomed mice over the evaluated time. However, histological analysis revealed evidence of pro-inflammatory processes occurring only at early times. Metabolomic analyses of urine samples identified taurine as a potential early biomarker of elevated oxidative stress and protein and creatinine levels.

Conclusions: P. lansbergii lansbergii venom induces alterations in murine renal tissue, affecting urinary biomarkers of kidney function within hours post-envenomation. Delayed proinflammatory effects may suggest an antioxidant imbalance in the envenomed mice, with unknown long-term effects. Further research on the role of oxidative stress and inflammation in renal structure and function following envenomation is necessary, emphasizing the need for prompt clinical management.