Oxaliplatin (
OXL) is a significant
therapy agent for the worldwide increase in
cancer cases.
Naringin (4',5,7-trihydroxy flavonon 7-rhamnoglucoside, NRG) has a wide range of
biological and pharmacological activities, including
antioxidant and anti-inflammatory potentials. This research aimed to investigate NRG activity in
OXL-induced hepatorenal toxicity. Accordingly,
OXL (4 mg/kg b.w.) in 5%
glucose was injected intraperitoneally on the first, second, fifth, and sixth days, and NRG (50 and 100 mg/kg b.w.) was given orally 30 min before to treatment. Biochemical, genetic, and histological methods were utilized to investigate the function tests,
oxidant/
antioxidant status,
inflammation, apoptosis, and endoplasmic reticulum (ER) stress pathways in kidney and liver tissues. Administration of NRG demonstrated an
antioxidant effect by increasing the activities of
OXL-induced reduced
antioxidant enzymes (
superoxide dismutase,
catalase, and
glutathione peroxidase) and decreasing the elevated lipid peroxidation parameter malondialdehyde levels. Nuclear factor-κB,
tumor necrosis factor-α, interleukin-1β, and inducible
nitric oxide synthase levels increased in
OXL administered groups but reduced in NRG-treated groups. In the
OXL-administered groups, NRG reduced the apoptosis-inducing factors
Caspase-3 and
B-cell lymphoma 2 (Bcl-2)-associated X
protein levels, while elevating the antiapoptotic factor Bcl-2 levels.
OXL triggered prolonged ER stress by increasing the levels of ER stress parameters
activating transcription factor 6,
protein kinase R-like ER
kinase,
inositol-requiring
enzyme 1α, and
glucose-regulated
protein 78. Therefore, with the NRG administration, this activity was reduced and the ER stress level decreased. Taken together, it was found that
OXL induced toxicity by increasing the levels of
urea and
creatinine,
alanine transaminase,
aspartate aminotransferase, and alkaline
phosphatase activities,
inflammation, apoptosis, ER stress, and
oxidants in the liver and kidney tissue, and NRG had a protective effect by reversing the deterioration in these pathways.