Monosodium Glutamate Induces Cytotoxicity in Rat Liver via Mitochondrial Permeability Transition Pore Opening
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ORIGINAL PAPER
Monosodium Glutamate Induces Cytotoxicity in Rat Liver via Mitochondrial Permeability Transition Pore Opening Adeola Oluwakemi Olowofolahan
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Oluwatobi Andrew Adeosun1 Olufunso Olabode Olorunsogo1 ●
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Accepted: 14 September 2020 / Published online: 23 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Monosodium glutamate (MSG) is a major food additive used as a flavor enhancer. A lot of controversies have been generated over the use of MSG. The present study therefore investigated whether MSG would induce cytotoxicity via the induction of mitochondrial permeability transition (mPT) pore opening. 36 male albino rats were used for this study. The rats were equally divided into six groups: group I is the control while group II, III, IV, V, and VI were orally treated with MSG (25, 50, 100, 200, and 400 mg/kg) daily for 28 days. The opening of the pore, cytochrome c release, mitochondrial ATPase activity, mitochondrial lipid peroxidation and hepatic DNA fragmentation were determined spectrophotometrically. Histological assessment of prostate and brain was carried out. The results show that MSG at concentrations ≤30 µg/ml did not induce mPT pore opening while higher concentrations caused significant induction of pore opening. Also, at lower doses (25 and 50 mg/kg), MSG did not cause any significant induction of mPT pore opening while at higher doses, there were significant induction of pore opening. Similar trend of results was recorded for cytochrome c release, mitochondrial ATPase activity and lipid peroxidation. The histological results show that at low doses (25 and 50 mg/kg), no significant lesion was observed while higher doses caused benign prostatic hyperplasia (BPH) in the prostate and necrotic damage in the brain. MSG administration at low dose is tolerable while high doses induce cytotoxicity via mPT pore opening. Keywords Monosodium glutamate Mitochondrial membrane permeability transition pore Apoptosis Cancer ●
Introduction Cytotoxicity could be assayed based on several cell functions especially mitochondrial membrane permeability transition, enzyme activity and ATP production [1]. Mitochondrial permeability transition (mPT) is an event which occurs when the inner mitochondrial membrane suddenly allows free passage of solutes up to 1.5 kDa in size [2]. This occurs as a result of the opening of mPT pore which leads to the collapse of inner membrane potential, ATP hydrolysis, cytochrome c release and ultimately, cell death [3]. Studies have shown that many synthetic and natural products induce cytotoxicity via induction of mPT pore opening in order to elicit their
* Adeola Oluwakemi Olowofolahan [email protected] 1
Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
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pharmacological effects against diseased conditions where apoptosis is deregulated [4, 5]. The opening and closing of mPT pore is a physiological event that is controlled in ord
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