# Nephroprotective Effects of Wedelolactone against Snake Venom-Induced Acute Kidney Injury: Insights into Experimental Envenomation

## TL;DR

This study explores how wedelolactone, a natural compound, can protect the kidneys from snake venom damage in rats, offering a potential new treatment for snakebite-induced kidney injury.

## Contribution

The study introduces wedelolactone as a nephroprotective agent against Bothrops envenomation-induced acute kidney injury in a preclinical model.

## Key findings

- Wedelolactone at 5 mg/kg preserved kidney function and reduced proteinuria in venom-treated rats.
- Histological and biochemical analyses showed reduced collagen deposition and nitrite levels with wedelolactone treatment.
- Higher doses of wedelolactone caused kidney injury in venom-treated rats but not in healthy ones.

## Abstract

Snakebite-induced acute kidney injury (sAKI) is a severe
clinical
complication associated with Bothrops envenomation
that can lead to kidney failure. Alternative therapies are needed
due to the limitations of antivenom, including variable efficacy,
risk of adverse reactions, and significant barriers to access, such
as long distances, transportation difficulties, and high costs. This
study evaluates the nephroprotective effects of wedelolactone (WEL),
a bioactive coumestan derived from Eclipta prostrata, known for its anti-inflammatory and antioxidant properties, in
a preclinical model of sAKI. Wistar rats were intramuscularly administered
3.5 mg/kg Bothrops jararacussu (Bj)
venom to induce sAKI, followed by treatment with WEL (2, 5, or 10
mg/kg) 2 h postenvenomation. At 5 mg/kg, WEL effectively mitigated
kidney dysfunction, preserving the glomerular filtration rate and
reducing proteinuria. Histological analysis revealed a preserved kidney
cytoarchitecture and reduced collagen deposition. Biochemical assays
indicated that WEL reduced matrix metalloproteinase activity and nitrite
levels, key mediators of Bj-induced nephrotoxicity, suggesting a protective
role via antioxidant mechanisms. However, WEL at 2 or 5 mg/kg did
not prevent Bj-induced muscle damage. Additionally, the 10 mg/kg dose
of WEL administered to Bj rats was associated with kidney injury,
limiting its potential for clinical application. Notably, WEL did
not impair kidney function in healthy rats. These findings underscore
the translational potential of WEL as a complementary therapeutic
approach for managing sAKI and reducing the long-term burden of snakebite-related
kidney disease.