The antioxidant N -(2-mercaptopropionyl)-glycine (tiopronin) attenuates expression of neuropathic allodynia and hyperalg
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ORIGINAL ARTICLE
The antioxidant N-(2-mercaptopropionyl)-glycine (tiopronin) attenuates expression of neuropathic allodynia and hyperalgesia Muhammad Shahid 1 & Fazal Subhan 2 & Nazar Ul Islam 1 & Nisar Ahmad 3 & Umar Farooq 1 & Sudhair Abbas 1 & Ihsan Ullah 4 & Naila Raziq 1 & Zia Ud Din 5 Received: 24 April 2020 / Accepted: 8 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The current pharmacotherapy of neuropathic pain is inadequate as neuropathic pain involves varied clinical manifestations with multifactorial etiology, modulated by a cascade of physical and molecular events leading to different clinical presentations of pain. There is an accumulating evidence of the involvement of oxidative stress in neuropathy, and antioxidants have shown promise in mitigating neuropathic pain syndromes. To explore the evidence supporting this beneficial proclivity of antioxidants, this study investigated the antinociceptive effectiveness of N-(2-mercaptopropionyl)glycine or tiopronin, a well-recognized aminothiol antioxidant, in a refined chronic constriction injury (CCI) rat model of neuropathic pain. Tiopronin (10, 30, and 90 mg/kg, i.p.) and pregabalin (30 mg/kg, i.p.) were administered daily after CCI surgery. The neuropathic paradigms of mechanical/cold allodynia and mechanical/heat hyperalgesia were assessed on days 3, 7, 14, and 21 post-nerve ligation. At the end of study, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were estimated in the sciatic nerve, dorsal root ganglion, and spinal cord for assessing the extent of oxidative stress. The expression of neuropathic nociception was attenuated by tiopronin which was observed as a significant attenuation of CCI-induced allodynia and hyperalgesia. Tiopronin reversed the neuronal oxidative stress by significantly reducing MDA, and increasing SOD, CAT, and GSH levels. Pregabalin also showed similar beneficial propensity on CCI-induced neuropathic aberrations. These findings suggest prospective neuropathic pain attenuating efficacy of tiopronin and further corroborated the notion that antioxidants are effective in mitigating the development and expression of neuropathic pain and underlying neuronal oxidative stress.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00210-020-01995-y) contains supplementary material, which is available to authorized users. * Muhammad Shahid [email protected]; [email protected]
Naila Raziq [email protected]
* Fazal Subhan [email protected]
Zia Ud Din [email protected]
Nazar Ul Islam [email protected]
1
Nisar Ahmad [email protected]
Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Khyber Pakhtunkhwa 25000, Pakistan
2
Umar Farooq [email protected]
Department of Pharmacy, CECOS University of IT and Emerging Sciences, Peshawar, Pakistan
3
Faculty of Pharmacy, National University of Pakistan, Sialkot, Punjab, Pakistan
4
De
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