Background:
This study examines the direct nephrotoxic effects of
Daboia
siamensis
venom (RVV) and venom fractions in
in
vivo
and isolated perfused kidneys (IPK) to understand the role
of inflammation pathways and susceptibility to oxidative stress in venom or
fraction-induced acute renal failure.
Methods:
We administered RVV and its venom fractions (PLA
2
, MP, LAAO, and
PDE) to rabbits
in vivo
and in the IPK model. We measured
oxidative stress biomarkers (SOD, CAT, GSH, and MDA) in kidney tissue, as
well as inflammatory cytokines (TNF-α, IL-1β, IFN-γ, IL-4, IL-5, and IL-10),
MDA and GSH levels in plasma and urine. We also calculated fractional
excretion (FE) for pro-/anti-inflammatory cytokines and oxidative stress
biomarkers, including the ratios of pro-/anti-inflammatory cytokines in
urine after envenomation.
Results:
In both kidney models, significant increases in MDA, SOD, CAT, and GSH
levels were observed in kidney tissues, along with elevated concentrations
of MDA and GSH in plasma and urine after injecting RVV and venom fractions.
Moreover, RVV injections led to progressive increases in FE
MDA
and decreases in FE
GSH.
The concentrations of IL-4, IL-5, IL-10,
IFN-γ, and TNF-α in plasma increased
in vivo
, as well as in
the urine of the IPK model, but not for IL-1β in both plasma and urine after
RVV administrations. Urinary fractional excretion of TNF-α, IL-1β, IFN-γ,
IL-4, IL-5, and IL-10 tended to decrease
in vivo
but showed
elevated levels in the IPK model. A single RVV injection
in
vivo
disrupted the balance of urinary cytokines, significantly
reducing either the TNF-α/IL-10 ratio or the IFN-γ/IL-10 ratio.
Conclusion:
RVV induces renal tubular toxicity by increasing oxidative stress production
and elevating inflammatory cytokines in urine. During the acute phase of
acute kidney injury, the balance of urine cytokines shifts toward
anti-inflammatory dominance within the first two hours post-RVV and venom
fractions.