Oral Supplements of Aqueous Extract of Tomato Seeds Alleviate Motor Abnormality, Oxidative Impairments and Neurotoxicity Induced by Rotenone in Mice: Relevance to Parkinson’s Disease

Abstract

Although tomato seeds (an industrial by-product) are known to contain several bioactive compounds, studies describing their health effects are limited. Previously, we evidenced that aqueous extract of tomato seeds (TSE) markedly attenuated rotenone (ROT)-induced oxidative stress and neurotoxicity in Drosophila system. This study investigated the neuroprotective effect of TSE in a chronic ROT model of neurotoxicity in mice. Initially, we assessed the potential of oral supplements of TSE to modulate the levels of endogenous markers of oxidative stress in brain regions of mice. Subsequently, employing a co-exposure paradigm, the propensity of TSE (100 mg/kg bw, 3 weeks) to attenuate ROT-induced behavioral phenotype (gait abnormalities, anxiety-like state), oxidative dysfunctions and neurotoxicity was examined. We found that mice provided with TSE supplements exhibited progressive improvement in gait pattern and exploratory behavior. TSE markedly offset ROT-induced oxidative impairments, restored reduced glutathione levels, antioxidant defenses (superoxide dismutase, glutathione peroxidase) and protein carbonyls content in brain regions. Specifically, TSE effectively diminished ROT induced elevation in the activity levels of acetylcholinesterase and restored the dopamine levels in striatum. Interestingly, in mitochondria, TSE was able to restore the activity of mitochondrial complexes and redox state. Collectively, our findings in the chronic ROT model demonstrate the ability of TSE to alleviate behavioral phenotype, oxidative stress, mitochondrial dysfunction and neurotoxicity. Further studies in dopaminergic cell models are necessary to understand the precise molecular mechanism/s by which tomato seed bioactives offer significant neuroprotection.

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“…All the brain regions were stored at 280 uC until further processing for isolation of the cytosol and subsequently for biochemical estimations and neurochemical quantification. Anxiety-like behaviour was evaluated by an elevated plus maze test, as described previously (Gokul & Muralidhara, 2014). The maze con- Sample preparation and biochemical analysis.…”

“…ROS production was measured using a 29,79-dichlorodihydrofluorescein diacetate (H 2 DCF-DA, Sigma-Aldrich) assay. H 2 DCF-DA is de-esterified to its polar derivative by intracellular esterases and subsequently oxidized to the fluorescent compound 29,79-dichlorofluorescein (DCF) by ROS (Gokul & Muralidhara, 2014). Briefly, reaction mixture (1 ml) containing Locke's buffer [154 mM NaCl, 5.6 mM KCl, 3.6 mM NaHCO 3 , 2.3 mM CaCl 2 , 5.6 mM D-glucose, 5 mM HEPES (pH 7.4)], sample (100 mg equivalent protein) and 10 ml DCFH-DA (5 mM) was incubated for 15 min at room temperature.…”

Recent developments in solid lipid nanoparticle and surface-modified solid lipid nanoparticle delivery systems for oral delivery of phyto-bioactive compounds in various chronic diseases

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Pesticides and Parkinson’s disease: A potential hazard in agricultural communities

“…had neuroprotective effects in rotenone-induced Parkinsonism in animals. [65][66][67][68][69][70][71] However, the roles of these agents in humans needs more studies.…”