The Neuroprotective Effect of Mesna on Cisplatin-Induced Neurotoxicity: Behavioral, Electrophysiological, and Molecular
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ORIGINAL ARTICLE
The Neuroprotective Effect of Mesna on Cisplatin‑Induced Neurotoxicity: Behavioral, Electrophysiological, and Molecular Studies Hakimeh Saadati1,2 · Somayeh Noroozzadeh3 · Hedieh Esmaeili3 · Keyvan Amirshahrokhi4 · Javad Shadman1,2 · Ali Niapour5 Received: 24 June 2020 / Revised: 7 November 2020 / Accepted: 15 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Peripheral neuropathy and cognitive impairments following cisplatin administration may interfere with the clinical usage of the drug. Mesna is a chemoprotective agent with anti-inflammatory and anti-oxidant effects. Our study aimed to investigate the protective effects of mesna against cisplatin-induced neurotoxicity. Neurotoxicity was induced by the administration of 2.5 mg/kg cisplatin twice a week for four consecutive weeks in male Wistar rats. The neuroprotective effect of mesna (150 mg/ kg/day) was evaluated through behavioral, electrophysiological, and molecular studies. Cisplatin treatment caused passive avoidance memory impairment, increased anxiety-like behaviors, altered thermal sensitivity, and decreased muscle strength in a grip strength test. Our electrophysiological studies indicated that administration of cisplatin induced peripheral sensory neuropathy and decreased the amplitudes of the compound action potential of sensory nerves. Cisplatin administration increased MDA and 4-HNE levels and decreased anti-oxidant (SOD and GPx) enzymes. Proinflammatory cytokines (IL-1β and TNF-α) and metalloproteinase-2 and 9 (MMP-2/9) were increased by cisplatin treatment. Morphological alterations were observed in the dorsal root ganglion (DRG) of cisplatin-treated rats. Cognitive impairments, anxiety, muscle strength, and thermal sensitivity changes induced by cisplatin were improved with mesna treatment. The reduced conduction velocity in sensory nerves was recovered in the cisplatin + mesna group. Mesna partially alleviated redox imbalance, reduced the proinflammatory cytokines, and MMP-2/9 levels. Mesna administration also relieved the morphological changes in DRG of cisplatin-treated rats. In conclusion, our results revealed that mesna can alleviate cisplatin-induced central and peripheral nervous system toxicity. These results support the concept that chemotherapy-induced neuropathy can be partially inhibited via mesna. Keywords Cisplatin-induced neuropathy · Mesna · Nerve conduction velocity · Oxidative stress · Inflammation · Dorsal root ganglion Somayeh Noroozzadeh and Hedieh Esmaeili contributed equally to this work * Ali Niapour [email protected]; [email protected] 1
Department of Physiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
2
Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
3
Department of Biochemistry, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
4
Department of Pharmacology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
5
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