Page 233 - EJMO-9-2

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

1. Introduction culminates in liver cell damage and loss of liver function,
a condition that, if left untreated, will lead to acute liver
A wide variety of viral infections, toxic substances, specific failure. Oxidative stress is defined as the condition that
drugs, and herbal or novel pharmaceutical products results from the disequilibrium between the generation
can result in acute liver injury (ALI). ALI pathogenesis of ROS and the body’s capacity to detoxify these reactive
comprises a complex array of centrally interconnected products readily. Primary roles in the pathophysiology of
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cascading processes – hepatocellular degeneration, biliary various liver disorders, including ALI, can be attributed
stasis, and inflammation – that ultimately lead to clinical to oxidative stress. Flavonoids, including quercetin, can
manifestations, including jaundice and hepatic function neutralize ROS to protect against cellular damage, mainly
impairment. Given the liver’s central role in metabolism, in hepatic tissues. In this regard, flavonoids, including
1
protein synthesis, and detoxification, liver disease may lead quercetin, may protect the liver cells from oxidative stress,
to severe systemic consequences and should be considered reduce inflammation, and enhance liver tissue regeneration
a critical determinant of body homeostasis. 2
through an antioxidative mechanism. In this context, the
Paracetamol overdose is considered one of the most biotransformations and biological effects of quercetin make
important causes of ALI as it is strongly related to fatal it a potential candidate with highly effective multipreventive
hepatic failure. Paracetamol is one of the most popular effects against hepatic lesions. Hence, quercetin, a flavonoid
3
analgesic agents worldwide for its ability to relieve pain and that exists naturally in many fruits and vegetables, such
reduce fever. It is a safe and efficient treatment when used as apples, grapes, onions, and broccoli, is an attractive
within therapeutic doses. However, the drug has a relatively prospect in treating liver diseases, providing preventive
low therapeutic index and can induce toxicity with relatively and therapeutic effects in hepatic lesions. Flavonoids are
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minor deviations from the recommended dosage. A high one of the most studied classes of bioactive compounds
propensity of overdose and subsequent liver damage is and are effective against oxidative stress-induced cellular
directly associated with a narrow therapeutic index, where damage, particularly in hepatic tissues. Quercetin is
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the margin between an effective and a toxic dose is small. known to neutralize the formation of ROS, downregulate
The hepatotoxic effects of paracetamol are a consequence pro-inflammatory cytokines and lipid peroxidation, and
of metabolic activation in the liver through the cytochrome enhance the activities of endogenous antioxidant enzymes,
P450 enzymatic system, leading specifically to the generation including superoxide dismutase and catalase. 8,9
of N-acetyl-p-benzoquinone imine (NAPQI), a highly
reactive toxic metabolite. The potentially toxic metabolite Hence, further research is needed to study the potential
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NAPQI is effectively scavenged by the readily available liver hepatoprotective effects of quercetin. Available literature
antioxidant glutathione (GSH) through conjugation with has shown that flavonoids, such as quercetin, exhibit liver-
GSH to form an inactive conjugate, which is excretable and protective effects, with good bioavailability profiles further
thus non-toxic. This activity restores cellular homeostasis supporting their possible candidacy as promising agents.
from any aberration that may result in cell damage. However, Such treatment allows the maintenance of mitochondrial
in the event of an overdose, NAPQI is generated at a rate that function and the prevention of hepatocyte apoptosis,
exceeds the scavenging capacity of GSH, thus resulting in two critical factors for an effective strategy to reduce
11,12
the depletion of GSH reserves. This condition compromises acetaminophen-induced liver injury. By reducing
the normal detoxification processes, allowing more NAPQI oxidative damage, preserving mitochondrial function, and
to diffuse into the hepatocytes. preventing hepatocyte apoptosis, quercetin may serve as
an effective strategy for reducing drug-induced liver injury.
Once formed, NAPQI covalently binds to cellular Therefore, this study aims to elucidate the hepatoprotective
proteins, interfering with their normal function and properties of quercetin in mitigating paracetamol-induced
triggering a cascade of harmful downstream processes. liver damage using an experimental rat model. 13,14
The resulting oxidative stress damages essential cellular
components – lipids, proteins, and nucleic acids – with 2. Materials and methods
the mitochondria exhibiting some of the earliest changes 2.1. Materials
in acetaminophen-induced liver toxicity. Mitochondrial
dysfunction further increases reactive oxygen species (ROS) The details of the materials used in this study are tabulated
production, a condition described as a vicious cycle of in Table 1.
damage. In addition, fragmentation of nuclear DNA – an
indication of cell injury – caused by NAPQI accumulation 2.2. Methods
results in the activation of apoptotic pathways, leading This study was approved by the Scientific Research Ethics
to necrosis and apoptosis of hepatocytes. This eventually Committee at Al-Kafeel University (Approval No. 2022 – 7).

Volume 9 Issue 2 (2025) 225 doi: 10.36922/ejmo.7873