Neuroprotective Effects of Guarana (Paullinia Cupana Mart.) Against Vincristine in Vitro Exposure

Abstract

Background: Vincristine (VCR) is not a specific chemotherapeutic drug, responsible for cause several side effects. In this sense, many natural products have been studied to reduce this problem. Objetives: To examine the guarana neuroprotective effect in mice brain and cerebellum cells against vincristine (VCR) exposition. Design: An in vitro study was performed using mice brain and cerebellum mice in monolayer culture. First, cells were exposed to VCR (0.009 µM for 24 hours and 0.0007 µM for 72 hours) to measure the cytotoxicity effect. Also, the cellular effect of hydroalcoholic extract of guarana (10; 30; 100 and 300 μg/mL) was evaluated in the same cells in 24 and 72 hours. After that, cells were exposed to VCR and guarana extract to evaluate the neuroprotective effect of guarana. Measurements: Cell viability was analyzed by MTT, Free dsDNA and LHD Assays. Moreover, metabolism oxidative profile was evaluated by reactive oxygen species (ROS), lipoperoxidation (LPO) and catalase (CAT) levels through DCFH-DA, TBARS and Catalase Activity Assays, respectively. Results: Our findings revealed that VCR caused neuronal cytotoxicity by reducing cell viability and increasing ROS and LPO levels. On the other hand, guarana did not cause cell damage in none of tested concentrations. In addition, guarana exhibited a notable protective effect on brain and cerebellum cells exposed to VCR by increasing cell viability, stimulating CAT activity, reducing levels of ROS and LPO. Conclusions: In this sense, guaraná is a remarkable antioxidant fruit that could be a target in new therapies development to reduce VCR neurotoxicity.

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“…Evidence has shown that guaraná presents strong antioxidant and radical‐ scavenging properties (Maldaner et al, 2020 ; Roggia et al, 2020 ; Santana & Macedo, 2018 ; Yonekura et al, 2016 ), protective cellular and anti‐inflammatory properties (Machado et al, 2021 ), neuroprotective effect (Veloso et al, 2018 ), and anti‐aging proprieties (Arantes et al, 2018 ) An epidemiological study reported guaraná habitual consumption by older adult riverine with a lower prevalence of hypertension, obesity, and metabolic syndrome (da Costa Krewer et al, 2011 ). Yonekura et al ( 2016 ) had shown that small daily doses of guaraná (3 g) can improve oxidative stress markers in healthy subjects (Yonekura et al, 2016 ).…”

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“…In addition, vincristine increases ROS production and causes a cellular imbalance in different brain regions in rats, via lipoperoxidation (Martins et al, 2011), indicating a close relationship between vincristine and oxidative stress, since ROS is a major contributor to neurodegeneration. In a study, using cerebral and cerebellar cells from mice exposed to vincristine (0.009 μM for 24 h and 0.0007 μM for 72 h), the hydroalcoholic extract of guarana (10, 30, 100 and 300 μg/mL) increased cell viability by stimulating CAT activity (10, 30 and 100 μg/mL), as well as reducing ROS and lipoperoxidation levels (Veloso et al, 2017) (Figure 3).…”

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“…The neuroprotective effect of guarana in mouse cerebellar cells and brain neurons against vincristine exposure was investigated in an in vitro study. P. cupana increased cell viability, stimulated catalase activity, and reduced lipoperoxidation and ROS levels [ 171 ]. The effects of P. cupana consumption on erythrocyte antioxidant enzyme activity, plasma catechins, and oxidative stress biomarkers in healthy, overweight subjects were evaluated.…”