Effect of tangeretin on cisplatin-induced oxido-inflammatory brain damage in rats.
Betul CicekBetul DanismanIsmail BolatMetin KilicliogluMehmet KuzucuHalis SuleymanKonstantinos TsarouhasAristidis TsatsakisAli TaghizadehghalehjoughiPublished in: Journal of cellular and molecular medicine (2024)
Cisplatin (CIS) is a platinum-derived chemotherapeutic agent commonly utilized in the treatment of various malignant tumours. However, anticancer doses of the drug cause serious damage to the brain. This study aimed to determine the potential protective effects of tangeretin, which has antioxidant and anti-inflammatory properties, in cisplatin-induced neurotoxicity on BALB/c mice brains. Male BALB/c mice were randomized and separated into four groups. Tangeretin was given for 10 days by gavage. CIS was injected as a single dose of 10 mg/kg intraperitoneally (ip) on the 10th day. Brain tissues, malondialdehyde (MDA), total glutathione (tGSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and nitric oxide (NO) levels were measured to determine oxidative damage and myeloperoxidase, tumour necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), IL-6 and IL-10 were measured to determine inflammatory activity. In addition, 8-OHdG and caspase-3 were analysed by immunofluorescence methods. While CIS administration remarkably elevated reactive oxygen species, MDA, and NO levels in brain tissue compared to the control, tGSH, GPx, SOD and CAT levels were significantly decreased. Also, it has been detected that TNF-α, IL-1β and IL-6 obtained in CIS-treated groups increased as well as IL-10 decreased, thereby elevating the inflammatory response. In addition, 8-OHdG and caspase-3 immunoreactivity in neurons increased with CIS administration. Treatment with tangeretin ameliorated the deterioration in oxidant/antioxidant status, overpowered neuroinflammation and ameliorated neurotoxicity-induced apoptosis. This study shows that tangeretin has beneficial effects on CIS-induced neurodegeneration. Possible mechanisms underlying these beneficial effects include the antioxidant and anti-inflammatory properties of tangeretin.
Keyphrases
- anti inflammatory
- oxidative stress
- induced apoptosis
- nitric oxide
- white matter
- resting state
- inflammatory response
- rheumatoid arthritis
- cell death
- cerebral ischemia
- endoplasmic reticulum stress
- functional connectivity
- hydrogen peroxide
- randomized controlled trial
- signaling pathway
- metabolic syndrome
- clinical trial
- emergency department
- lps induced
- multiple sclerosis
- double blind
- spinal cord injury
- brain injury
- climate change
- risk assessment
- spinal cord
- amyotrophic lateral sclerosis
- study protocol
- stress induced
- drug induced
- phase iii
- subarachnoid hemorrhage
- endothelial cells
- blood brain barrier
- placebo controlled
- phase ii
- adverse drug
- electronic health record