Effect of quercetin and role of nitric oxide pathway in chloroquine-induced scratching
DOI:
https://doi.org/10.1590/s2175-97902023e201085Keywords:
Chloroquine-induced itch, Quercetin, Nitrergic system, ScratchingAbstract
Nitric oxide (NO) is an abundant mediator which is demonstrated to be involved in pruritus. Assuming that the increased NO also mediates chloroquine-induced pruritus, which is a frequent complication seen in the chronic chloroquine treatment, the current study aimed to investigate the effect of quercetin and the role of NO in chloroquine-induced pruritus in C57BL/6 mice. Model was created with subcutaneous chloroquine (400µg/site) injection to the nape of the mice. Effect of quercetin and role of NO were investigated with administration of quercetin, and co-administration with L-NAME, 7-NI and L-arginine before chloroquine injection. Locomotor activity was assessed by activity cage and number of the scratching bouts after chloroquine injection was recorded for 30 minutes. Our results show that quercetin significantly reduced scratching bouts at the doses of 10, 20, 40 and 80 mg/kg. Locomotor activity was decreased at the 40 and 80 mg/kg doses of quercetin. Additionally, decrease of the number of scratching bouts by quercetin prevented by L-arginine treatment, while L-NAME and 7-NI enhanced the anti-pruritic effect of sub-effective doses of quercetin. Therefore, our study demonstrated that acute injection of quercetin significantly diminished chloroquine-induced scratching behavior, and this effect is partly mediated by inhibition of neuronal nitric oxide synthase enzyme.
Downloads
References
Akiyama T, Carstens E. Neural processing of itch. Neuroscience. 2013;250:697-714.
Anand David AV, Arulmoli R, Parasuraman S. Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid. Pharmacogn Rev. 2016;10(20):84-9.
Andoh T, Kuraishi Y. Nitric oxide enhances substance P-induced itch-associated responses in mice. Br J Pharmacol. 2003;138(1):202-8.
Bush MA, Pollack GM. Pharmacokinetics and pharmacodynamics of 7-nitroindazole, a selective nitric oxide synthase inhibitor, in the rat hippocampus. Pharm Res. 2001;18(11):1607-12.
Chen R, Lin J, Hong J, Han D, Zhang AD, Lan R, et al. Potential toxicity of quercetin: The repression of mitochondrial copy number via decreased POLG expression and excessive TFAM expression in irradiated murine bone marrow. Toxicol Rep. 2014;1:450-8.
Cho YJ, Kim SJ. Effect of quercetin on the production of nitric oxide in murine macrophages stimulated with lipopolysaccharide from Prevotella intermedia. J Periodontal Implant Sci. 2013;43(4):191-7.
Davidson S, Giesler GJ. The multiple pathways for itch and their interactions with pain. Trends in Neurosciences. 2010;33(12):550-8.
Domagala A, Szepietowski J, Reich A. Antihistamines in the treatment of pruritus in psoriasis. Postepy Dermatol Alergol. 2017;34(5):457-63.
Dos Reis Neto ET, Kakehasi AM, de Medeiros Pinheiro M, Ferreira GA, Marques CDL, da Mota LMH, et al. Revisiting hydroxychloroquine and chloroquine for patients with chronic immunity-mediated inflammatory rheumatic diseases. Adv Rheumatol. 2020;60(1):32.
Ebihara N, Takahashi K, Takemura H, Akanuma Y, Asano K, Sunagawa M. Suppressive effect of quercetin on nitric oxide production from nasal epithelial cells in vitro. Evid Based Complement Alternat Med. 2018;2018:6097625.
Foroutan A, Haddadi NS, Ostadhadi S, Sistany N, Dehpour AR. Chloroquine-induced scratching is mediated by NO/ cGMP pathway in mice. Pharmacol Biochem Behav. 2015;134:79-84.
Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. European Heart J. 2011;33(7):829-37.
Furue K, Ulzii D, Tanaka Y, Ito T, Tsuji G, Kido-Nakahara M, et al. Pathogenic implication of epidermal scratch injury in psoriasis and atopic dermatitis. J Dermatol. 2020;47(9):979-88.
Goromaru T, Itoh Y, Sendo T, Kobayashi K, Yano T, Ikesue H, et al. Ovariectomy aggravates hypersensitivity reactions to paclitaxel in rats. Cancer Biol Ther. 2005;4(2):225-30.
Guran M, Sanliturk G, Kerkuklu NR, Altundag EM, Suha Yalcin A. Combined effects of quercetin and curcumin on anti-inflammatory and antimicrobial parameters in vitro. Eur J Pharmacol. 2019;859:172486.
Haddadi NS, Shakiba S, Afshari K, Haj-Mirzaian A, Vesaghati S, Gharagozlou S, et al. Possible Involvement of Nitric Oxide in the Antipruritic Effect of Metformin on Chloroquine-Induced Scratching in Mice. Dermatology. 2020;236(2):151-9.
Hassanipour M, Shirzadian A, Boojar MM, Abkhoo A, Abkhoo A, Delazar S, et al. Possible involvement of nitrergic and opioidergic systems in the modulatory effect of acute chloroquine treatment on pentylenetetrazol induced convulsions in mice. Brain Res Bull. 2016;121:124-30.
Heinzen EL, Pollack GM. Pharmacokinetics and pharmacodynamics of L-arginine in rats: a model of stimulated neuronal nitric oxide synthesis. Brain Res. 2003;989(1):67-75.
Jafarinia M, Sadat Hosseini M, Kasiri N, Fazel N, Fathi F, Ganjalikhani Hakemi M, et al. Quercetin with the potential effect on allergic diseases. Allergy Asthma Clin Immunol. 2020;16:36.
Kanazawa LKS, Vecchia DD, Wendler EM, Hocayen PdAS, Beirão PS, de Mélo ML, et al. Effects of acute and chronic quercetin administration on methylphenidate-induced hyperlocomotion and oxidative stress. Life Sci. 2017;171:1-8.
Kanazawa LKS, Vecchia DD, Wendler EM, Hocayen PdAS, dos Reis Lívero FA, Stipp MC, et al. Quercetin reduces manic-like behavior and brain oxidative stress induced by paradoxical sleep deprivation in mice. Free Radic Biol Med. 2016;99:79-86.
Kao TK, Ou YC, Raung SL, Lai CY, Liao SL, Chen CJ. Inhibition of nitric oxide production by quercetin in endotoxin/cytokine-stimulated microglia. Life Sci . 2010;86(9-10):315-21.
Ko MC. Roles of Central Opioid Receptor Subtypes in Regulating Itch Sensation. In: Carstens E, Akiyama T, editors. Itch: Mechanisms and Treatment. Frontiers in Neuroscience . Boca Raton (FL)2014.
Lee B, Yeom M, Shim I, Lee H, Hahm DH. Protective Effects of Quercetin on Anxiety-Like Symptoms and Neuroinflammation Induced by Lipopolysaccharide in Rats. Evid Based Complement Alternat Med . 2020;2020:4892415.
Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, et al. Quercetin, inflammation and immunity. Nutrients. 2016;8(3):167.
Maramaldi G, Togni S, Pagin I, Giacomelli L, Cattaneo R, Eggenhoffner R, et al. Soothing and anti-itch effect of quercetin phytosome in human subjects: a single-blind study. Clin Cosmet Investig Dermatol. 2016;9:55-62.
Miyahara Y, Funahashi H, Naono-Nakayama R, Haruta-Tsukamoto A, Muroi C, Kogoh Y, et al. Serotonin and noradrenaline modulate chronic itch processing in mice. Eur J Pharmacol . 2020;883:173319.
Ostadhadi S, Foroutan A, Haddadi NS, Norouzi-Javidan A, Momeny M, Zarrinrad G, et al. Pharmacological evidence for the involvement of adenosine triphosphate sensitive potassium channels in chloroquine-induced itch in mice. Pharmacol Rep. 2017;69(6):1295-9.
Panthi S, Gautam K. Roles of nitric oxide and ethyl pyruvate after peripheral nerve injury. Inflamm Regen. 2017;37(1):20.
Reszke R, Krajewski P, Szepietowski JC. Emerging Therapeutic Options for Chronic Pruritus. Am J Clin Dermatol. 2020;21(5):601-18.
Taguchi K, Tano I, Kaneko N, Matsumoto T, Kobayashi T. Plant polyphenols Morin and Quercetin rescue nitric oxide production in diabetic mouse aorta through distinct pathways. Biomed Pharmacother. 2020;129:110463.
Tarrason G, Carcasona C, Eichhorn P, Perez B, Gavalda A, Godessart N. Characterization of the chloroquine-induced mouse model of pruritus using an automated behavioural system. Exp Dermatol. 2017;26(11):1105-11.
Wilson SR, Gerhold KA, Bifolck-Fisher A, Liu Q, Patel KN, Dong X, et al. TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch. Nat Neurosci. 2011;14(5):595-602.
Xu D, Hu MJ, Wang YQ, Cui YL. Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application. Molecules. 2019;24(6):1123.
Yin H, Ma J, Han J, Li M, Shang J. Pharmacokinetic comparison of quercetin, isoquercitrin, and quercetin-3-O-beta-D-glucuronide in rats by HPLC-MS. PeerJ. 2019;7:e6665.
Yu L, Derrick M, Ji H, Silverman RB, Whitsett J, Vásquez-Vivar J, et al. Neuronal Nitric Oxide Synthase Inhibition Prevents Cerebral Palsy following Hypoxia-Ischemia in Fetal Rabbits: Comparison between JI-8 and 7-Nitroindazole. Dev Neurosci. 2011;33(3-4):312-9.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on-line journal has open and free access.
