Effects of natural and synthetic isothiocyanate-based H2S-releasers against chemotherapy-induced neuropathic pain: Role of Kv7 potassium channels.

Title Effects of natural and synthetic isothiocyanate-based H2S-releasers against chemotherapy-induced neuropathic pain: Role of Kv7 potassium channels.
Authors L.Di Cesare Mannelli; E. Lucarini; L. Micheli; I. Mosca; P. Ambrosino; M.Virginia Soldovieri; A. Martelli; L. Testai; M. Taglialatela; V. Calderone; C. Ghelardini
Journal Neuropharmacology
DOI 10.1016/j.neuropharm.2017.04.029
Abstract

Hydrogen sulfide (H2S) is a crucial signaling molecule involved in several physiological and pathological processes. Nonetheless, the role of this gasotransmitter in the pathogenesis and treatment of neuropathic pain is controversial. The aim of the present study was to investigate the pain relieving profile of a series of slow releasing H2S donors (the natural allyl-isothiocyanate and the synthetics phenyl- and carboxyphenyl-isothiocyanate) in animal models of neuropathic pain induced by paclitaxel or oxaliplatin, anticancer drugs characterized by a dose-limiting neurotoxicity. The potential contribution of Kv7 potassium channels modulation was also studied. Mice were treated with paclitaxel (2.0 mg kg(-1)) i.p. on days 1, 3, 5 and 7; oxaliplatin (2.4 mg kg(-1)) was administered i.p. on days 1-2, 5-9, 12-14. Behavioral tests were performed on day 15. In both models, single subcutaneous administrations of H2S donors (1.33, 4.43, 13.31 ?mol kg(-1)) reduced the hypersensitivity to cold non-noxious stimuli (allodynia-related measurement). The prototypical H2S donor NaHS was also effective. Activity was maintained after i.c.v. administrations. On the contrary, the S-lacking molecule allyl-isocyanate did not increase pain threshold; the H2S-binding molecule hemoglobin abolished the pain-relieving effects of isothiocyanates and NaHS. The anti-neuropathic properties of H2S donors were reverted by the Kv7 potassium channel blocker XE991. Currents carried by Kv7.2 homomers and Kv7.2/Kv7.3 heteromers expressed in CHO cells were potentiated by H2S donors. Sistemically- or centrally-administered isothiocyanates reduced chemotherapy-induced neuropathic pain by releasing H2S. Activation of Kv7 channels largely mediate the anti-neuropathic effect.

Citation L.Di Cesare Mannelli; E. Lucarini; L. Micheli; I. Mosca; P. Ambrosino; M.Virginia Soldovieri; A. Martelli; L. Testai; M. Taglialatela; V. Calderone; C. Ghelardini.Effects of natural and synthetic isothiocyanate-based H2S-releasers against chemotherapy-induced neuropathic pain: Role of Kv7 potassium channels.. Neuropharmacology. 2017;121:4959. doi:10.1016/j.neuropharm.2017.04.029

Related Elements

Potassium

Elemental PotassiumSee more Potassium products. Potassium (atomic symbol: K, atomic number: 19) is a Block S, Group 1, Period 4 element with an atomic weight of 39.0983. The number of electrons in each of Potassium's shells is [2, 8, 8, 1] and its electron configuration is [Ar] 4s1. The potassium atom has a radius of 227.2 pm and a Van der Waals radius of 275 pm. Potassium was discovered and first isolated by Sir Humphrey Davy in 1807. Potassium is the seventh most abundant element on earth. It is one of the most reactive and electropositive of all metals and rapidly oxidizes. As with other alkali metals, potassium decomposes in water with the evolution of hydrogen because of its reacts violently with water, it only occurs in nature in ionic salts.Potassium Bohr Model In its elemental form, potassium has a silvery gray metallic appearance, but its compounds (such as potassium hydroxide) are more frequently used in industrial and chemical applications. The origin of the element's name comes from the English word 'potash,' meaning pot ashes, and the Arabic word qali, which means alkali. The symbol K originates from the Latin word kalium.

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