Biochemical and histological alterations of doxorubicin‐induced neurotoxicity in rats: Protective role of luteolin

Doxorubicin (DOX) is a chemotherapeutic drug used in the treatment of various cancer types. DOX toxic side effects include neuronopathy and memory deficits. We investigated the effect of the antioxidant luteolin (LUT: 50 or 100 mg/kg; per os) on DOX (2 mg/kg; intraperitoneal)‐induced oxidative stres...

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Bibliographic Details
Published in:Journal of biochemical and molecular toxicology 2022-03, Vol.36 (3), p.e22962-n/a
Main Authors: Imosemi, Innocent O., Owumi, Solomon E., Arunsi, Uche O.
Format: Article
Language:English
Subjects:
Animals
Antioxidants
Apoptosis
Biomarkers
Caspase
Catalase
Chemotherapy
Cytokines
Doxorubicin
Doxorubicin - adverse effects
Doxorubicin - pharmacology
Glutathione
Glutathione peroxidase
Inflammation
Interleukins
Lipid peroxidation
Lipids
Luteolin - pharmacology
luteolin‐antioxidant
Male
Neurotoxicity
Neurotoxicity Syndromes - metabolism
Neurotoxicity Syndromes - prevention & control
Nitric oxide
Organs
Oxidation
Oxidative stress
oxido‐inflammatory stress
Peroxidase
Peroxidation
Rats
Rats, Wistar
Reactive nitrogen species
Reactive oxygen species
Side effects
Superoxide dismutase
Supplements
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Summary:Doxorubicin (DOX) is a chemotherapeutic drug used in the treatment of various cancer types. DOX toxic side effects include neuronopathy and memory deficits. We investigated the effect of the antioxidant luteolin (LUT: 50 or 100 mg/kg; per os) on DOX (2 mg/kg; intraperitoneal)‐induced oxidative stress (OS), inflammation, and apoptosis in the brain of Wistar rats for 14 days. We observed that LUT reduced DOX‐mediated increase in OS biomarkers—catalase, superoxide dismutase, glutathione‐S‐transferase, and glutathione peroxidase. LUT increased glutathione and total sulphydryl levels and alleviated DOX‐induced increases in the levels of reactive oxygen and nitrogen species, lipid peroxidation, myeloperoxidase, nitric oxide, tumor necrosis factor‐α, and interleukin‐1β (IL‐1β). Additionally, LUT suppressed caspase‐3 activity, increased anti‐inflammatory cytokine—IL‐10 level, and reduced pathological lesions in the examined organs of rats cotreated with LUT and DOX. Collectively, cotreatment with LUT lessened DOX‐induced neurotoxicity. Supplementation of LUT as a chemopreventive agent might be useful in patients undergoing DOX chemotherapy.
ISSN:1095-6670
1099-0461
DOI:10.1002/jbt.22962