Page 238 - EJMO-9-2

Eurasian Journal of
Medicine and Oncology Quercetin effects in rats with liver injury

as an inhibitor of NF-κB, a transcription factor that
regulates the expression of genes involved in inflammatory
responses. Through this mechanism, quercetin suppresses
the production of pro-inflammatory cytokines.
Furthermore, quercetin downregulates the expression of
the two inflammatory mediators, cyclooxygenase-2 and
inducible nitric oxide synthase. These actions contribute
to the attenuation of hepatic inflammation and confer a
protective effect against liver injury. 23,24
Treatment with paracetamol significantly increased
the levels of GOT, GPT, TNF-α, NF-κB, and caspase-3
in the paracetamol-only group, indicating evident liver
injury and necrosis. A significant rise in MDA levels was
observed, suggesting that increased lipid peroxidation can
cause tissue damage. Reduced levels of GSH and BCL2
were also observed in this study. These findings aligned
with previous studies, which reported elevated serum
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GOT and GPT levels as urine markers and MDA levels in
tissue homogenates. 25
Quercetin may also alleviate hepatic complications
instigated by paracetamol. The manifestations of hepatic Figure 10. The role of nuclear factor kappa B in liver injury
complications are mostly revealed by enhanced serum GOT Abbreviations: NAPQI: N-acetyl-p-benzoquinone imine; NF-κB: Nuclear
factor kappa B; ROS: Reactive oxygen species.
and GPT activities and a rise in MDA level, a direct marker
for oxidative stress and liver damage. The normalization of
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biochemical parameters following quercetin administration downregulation of NF-κB-dependent mRNA expression,
strongly suggests its restorative potential in mitigating further supporting quercetin’s protective role against
29
liver toxicity. These findings align with earlier reports that hepatocellular inflammation and damage.
demonstrated a marked decrease in the elevated plasma TNF-α is one of the key cytokines in the immune
levels of GOT and GPT activities and MDA levels following response, particularly in liver injury, where its local effects
quercetin treatment before hepatic ischemia-reperfusion are significant. Upregulated shortly after cellular injury,
injury. The results provide evidence for quercetin’s TNF-α initiates the inflammatory cascade, modulating
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therapeutic potential in hepatoprotection, including its tissue responses to injury. This cytokine actively recruits and
efficacy against paracetamol-induced liver injury. activates immune cells such as neutrophils, macrophages,
The NF-κB pathway plays a key role in the development and T lymphocytes, which in turn produce a wide array
of hepatocellular damage, mainly due to its sensitivity of pro-inflammatory mediators, including cytokines,
to various external factors, such as ROS, cytokines, or chemokines, and enzymes. This cascade of events amplifies
shear stress in the vasculature. The pathway is the main tissue damage, further compromising liver function by
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promoter of inflammation and stress response within the eliciting strong host defenses. TNF-α has been shown to
hepatocyte, and its activation exacerbates hepatocellular play a dual role, both in protective immune responses and
damage, as depicted in Figure 10. immune-mediated pathological tissue injury, as indicated
by its complex interactions between various cell types. 30
In the present study, levels of NF-κB were significantly
elevated in the active control group compared to the The present study showed a significant increase in
normal group, indicating that the upregulation of this the levels of TNF-α in the paracetamol-treated groups
pathway strongly relates to the progression of liver injury. compared to the untreated control. The elevation of
However, quercetin treatment effectively mitigated the TNF-α is a key marker for inflammation and hepatic
activation of NF-κB in the active control group, preventing injury in paracetamol-induced liver toxicity. In contrast,
further hepatic damage. This finding is consistent with rats treated with quercetin revealed a significant reduction
another study, which found that treatment with quercetin in TNF-α expression, highlighting its therapeutic potential
following the induction of hepatic injury caused a in reducing inflammation associated with liver damage.
notable reduction in NF-κB activation. The previous These findings align with similar studies, which indicated
31
study found that treatment with quercetin resulted in the that quercetin protects against liver injury.

Volume 9 Issue 2 (2025) 230 doi: 10.36922/ejmo.7873