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Carboplatin and thalidomide induced neuro-hepatotoxicity in rats: Diminish effect of Citrullus colocynthis

Carboplatin and thalidomide are good candidate’s treatments against many types of cancer. Latest studies demonstrated that these chemotherapeutic drug cause oxidative damage. So, the present study was conducted to estimate the neurotoxic and hepatotoxic effects induced by carboplatin/thalidomide regimen and to explore the potential protective effect of Citrillus colocynthis extract (CCE) in rats. The obtained results showed that carboplatin/thalidomide induced histological changes, caused significant elevation in serum liver enzymes, decline in brain and plasma neurotransmitters, and increase in acetylcholine esterase. At the molecular level, carboplatin/thalidomide caused marked elevation in inflammatory and apoptotic markers and suppressed the expression of proliferator-activated receptor-gamma coactivator-1 and mitochondrial transcription factor a in brain and liver tissues. Also, the regemin declined the GSH system and nuclear factor erythroid-2-related factor 2 (NRF2), and induced oxidative stress as indicated by elevated tissues level of thiobarbituric acid reactive substances and 8-hydroxydeoxyguanosine. The co-supplemnation with CCE minimized thalidomide/carboplatin-induced abnormalities in brain and liver tissues. As a result, the current findings revealed that CCE may have a protective effect against carboplatin/thalidomide-induced toxicity. structure, neurotransmitters, redox status, DNA damage, cytokine production, apoptosis and gene expression of genes regulating mitochondrial biogenesis; PGC-1α and mtTFA. This study provided solid evidences of the protective effects of CC extract against toxicity induced by carboplatin and thalidomide. CC extract is safe, efficient and promising therapeutic agent that can be effectively employed as natural therapeutic antioxidant for a wide range of applications in the field of food and medicine.