Subscribe to RSS
DOI: 10.1055/a-1589-5395
Evaluation of Anti-inflammatory and Antioxidant Effects of Sumatriptan on Carbon Tetrachloride-induced Hepatotoxicity in Rats
![](https://www.thieme-connect.de/media/drugres/202201/lookinside/thumbnails/2021-04-2282_10-1055-a-1589-5395-1.jpg)
Abstract
The liver detoxifies and metabolizes many drugs and xenobiotics which may cause hepatotoxicity due to some toxic agents. Carbon tetrachloride (CCl4) is metabolized in cytochrome P450 and its reactive radical metabolites cause lipid peroxidation, cellular injury, and apoptosis. Sumatriptan (SUM), 5-HT1B/1D receptor agonist, had anti-inflammatory and anti-oxidant effects. In this research the effect of SUM pre-treatment against CCl4-induced hepatotoxicity was examined. Adult rats received SUM (0.1, 0.3 and 1 mg/kg; i.p.) for 3 consecutive days before CCl4 (2 ml/kg; i.p. on the 3rd day). The aminotransferases serum levels, tissue levels of anti-oxidant and pro-inflammatory markers and histopathological examination were evaluated. SUM (0.3 mg/kg) prevented significantly the elevation of aminotransferases versus the control group (CCl4 group) (P<0.0001) and also, reversed meaningfully the changes of the MPO, MDA, SOD and CAT, IL-1β and TNF-α levels. Additionally, CCl4-intoxication resulted to the disruption of lobular and cellular structures and inflammation in histopathological evaluation which is prevented by SUM (0.3 mg/kg). These data revealed that SUM (0.3 mg/kg), but no at doses 0.1 and 1 mg/kg, decreases the hepatotoxicity of induced by CCl4 in rats.
Publication History
Received: 30 April 2021
Accepted: 09 August 2021
Article published online:
09 September 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Hafez MM. et al. Association between paraoxonases gene expression and oxidative stress in hepatotoxicity induced by CCl4. Oxidative medicine and cellular longevity 2014; 2014: 893212-893212
- 2 Yousefi-Manesh H. et al. Hepatoprotective Effects of Standardized Extracts from an Ancient Italian Apple Variety (Mela Rosa dei Monti Sibillini) against Carbon Tetrachloride (CCl(4))-Induced Hepatotoxicity in Rats. Molecules (Basel, Switzerland) 2020; 25: 1816
- 3 Yousefi-Manesh H. et al. Hepatoprotective effects of phosphatidylserine liposomes on carbon tetrachloride-induced hepatotoxicity in rats. J Cell Biochem. 2019
- 4 Lin S-Y. et al. Protective Effects of Salidroside against Carbon Tetrachloride (CCl(4))-Induced Liver Injury by Initiating Mitochondria to Resist Oxidative Stress in Mice. International journal of molecular sciences 2019; 20: 3187
- 5 Hafez MM. et al. Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats. Biological research 2015; 48: 30-30
- 6 Elsawy H. et al. Rutin ameliorates carbon tetrachloride (CCl(4))-induced hepatorenal toxicity and hypogonadism in male rats. PeerJ 2019; 7: e7011-e7011
- 7 Chen S. et al. Targeting Myeloperoxidase (MPO) Mediated Oxidative Stress and Inflammation for Reducing Brain Ischemia Injury: Potential Application of Natural Compounds. Frontiers in Physiology 2020; 11: 433
- 8 Prasanna PL, Renu K, Valsala A. Gopalakrishnan, New molecular and biochemical insights of doxorubicin-induced hepatotoxicity. Life Sci 2020; 250: 117599
- 9 Morio LA. et al. Distinct roles of tumor necrosis factor-alpha and nitric oxide in acute liver injury induced by carbon tetrachloride in mice. Toxicol Appl Pharmacol 2001; 172: 44-51
- 10 Bak J. et al. Oligonol Ameliorates CCl4-Induced Liver Injury in Rats via the NF-Kappa B and MAPK Signaling Pathways. Oxidative Medicine and Cellular Longevity 2016; 2016: 3935841
- 11 Safhi MM. Nephroprotective Effect of Zingerone against CCl(4)-Induced Renal Toxicity in Swiss Albino Mice: Molecular Mechanism. Oxidative medicine and cellular longevity 2018; 2018: 2474831-2474831
- 12 Bingham S. et al. Inhibition of Inflammation-Induced Thermal Hypersensitivity by Sumatriptan through Activation of 5-HT1B/1D Receptors. Experimental Neurology 2001; 167: 65-73
- 13 Sheibani M. et al. Sumatriptan protects against myocardial ischaemia–reperfusion injury by inhibition of inflammation in rat model. Inflammopharmacology 2019; 27: 1071-1080
- 14 Abramovitz B. et al. Bilateral renal infarctions during the use of sumatriptan. Kidney international reports 2018; 3: 1233-1236
- 15 Levy D, Jakubowski M, Burstein R. Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT1B/1D receptor agonists. Proceedings of the National Academy of Sciences 2004; 101: 4274-4279
- 16 Ferrari MD, Saxena PR. Clinical effects and mechanism of action of sumatriptan in migraine. Clinical neurology and neurosurgery 1992; 94: 73-77
- 17 Vera-Portocarrero LP. et al. Reversal of inflammatory and noninflammatory visceral pain by central or peripheral actions of sumatriptan. Gastroenterology 2008; 135: 1369-1378
- 18 Dejban P. et al. Protective effects of sumatriptan on ischaemia/reperfusion injury following torsion/detorsion in ipsilateral and contralateral testes of rat. Andrologia 2019; 51: e13358
- 19 Sadeghi H. et al. Hepatoprotective effect of Rosa canina fruit extract against carbon tetrachloride induced hepatotoxicity in rat. Avicenna journal of phytomedicine 2016; 6: 181-188
- 20 Peng C. et al. CCl4-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway. Evidence-Based Complementary and Alternative Medicine 2019; 2019: 5941263
- 21 Gooshe M. et al. Biphasic effect of sumatriptan on PTZ-induced seizures in mice: Modulation by 5-HT1B/D receptors and NOS/NO pathway. Eur J Pharmacol 2018; 824: 140-147
- 22 Afshari K. et al. Sumatriptan improves the locomotor activity and neuropathic pain by modulating neuroinflammation in rat model of spinal cord injury. Neurological Research 2021; 43: 29-39
- 23 Wang M. et al. Zerumbone Protects against Carbon Tetrachloride (CCl(4))-Induced Acute Liver Injury in Mice via Inhibiting Oxidative Stress and the Inflammatory Response: Involving the TLR4/NF-κB/COX-2 Pathway. Molecules (Basel, Switzerland) 2019; 24: 1964
- 24 Liu Y. et al. Breviscapine ameliorates CCl4–induced liver injury in mice through inhibiting inflammatory apoptotic response and ROS generation.. Int J Mol Med 2018; 42: 755-768
- 25 Scholten D. et al. The carbon tetrachloride model in mice . Laboratory animals 2015; 49: 4-11
- 26 Ullah H. et al. Poncirin attenuates CCL4-induced liver injury through inhibition of oxidative stress and inflammatory cytokines in mice. BMC Complementary Medicine and Therapies 2020; 20: 115
- 27 Nikai T, Basbaum AI, Ahn AH. Profound reduction of somatic and visceral pain in mice by intrathecal administration of the anti-migraine drug, sumatriptan. Pain 2008; 139: 533-540
- 28 Eltahir HM. et al. Antioxidant, anti‑inflammatory and anti‑fibrotic effects of Boswellia serrate gum resin in CCl4–induced hepatotoxicity.. Exp Ther Med 2020; 19: 1313-1321
- 29 Kandil YI. et al. Resveratrol pretreatment reduces circulating inflammatory interleukins in CCl4-induced hepatotoxicity rats. Bulletin of Faculty of Pharmacy. Cairo University 2017; 55: 319-323