Effect of WR-1065 on 6-hydroxydopamine-induced Catalepsy and IL-6 Level in Rats

Overview

Journal Iran J Basic Med Sci

Publisher Mashhad University of Medical Sciences

Specialty General Medicine

Date 2016 Jul 13

PMID 27403255

Citations 7

Authors

Afshin Kheradmand

Alireza Mohajjel Nayebi

Masoumeh Jorjani

Rasool Haddadi

Affiliations

Soon will be listed here.

Abstract

Objectives: Neuroinflammation and oxidative stress play a key role in pathogenesis of Parkinson's disease (PD). In the present study we investigated the effect of reactive oxygen species (ROS) scavenger WR-1065 on catalepsy and cerebrospinal fluid (CSF) level of interleukin 6(IL-6) and striatum superoxide dismutase (SOD) activity in 6-hydroxydopamine (6-OHDA) induced experimental model of PD.

Materials And Methods: Seventy two male Wistar rats were divided into 9 equal groups and 6-OHDA (8 μg/2 μl/rat) was infused unilaterally into substantia nigra pars copmacta (SNc) to induce PD. Catalepsy was measured by standard bar test, CSF level of IL-6 was assessed by enzyme-linked immunosorbent assay (ELISA) method and SOD activity measured by spectrophotometric method. In pre-treatment groups WR-1065 (20, 40 and 80 μg/2 μl/rat/day, for 3 days) was infused into the SNc before 6-OHDA administration and 21 days later, as a recovery period, behavioral and molecular assay tests were done.

Results: Our results showed that pre-treatment with WR-1065 improved (P<0.001) 6-OHDA-induced catalepsy in a dose dependent manner. In 6-OHDA-lesioned animals SOD activity in SNc and CSF level of IL-6 was decreased markedly (P<0.001) when compared with non-lesioned group, while pre-treatment with WR-1065(P<0.001) restored their levels up to the normal range.

Conclusion: Our study indicated that pre-treatment with WR-1065 could modulate catalepsy and IL-6 level in 6-OHDA-lesioned rats. Also WR1065 could increase SOD activity up to normal range. It can be regarded as an anti-oxidative drug in prevention or adjunctive therapy of PD.

Citing Articles

Acute Treatment with Fucoidan Ameliorates Traumatic Brain Injury-Induced Neurological Damages and Memory Deficits in Rats: Role of BBB Integrity, Microglial Activity, Neuroinflammation, and Oxidative Stress.

Eyvari-Brooshghalan S, Haddadi R, Shahidi S, Ghaderi S, Rashno M, Kalantari A Mol Neurobiol. 2024; .

PMID: 39692820 DOI: 10.1007/s12035-024-04668-6.

The role of histamine H receptor in the anterior cingulate cortex on nociception level following acute restraint stress in male rats.

Daniali R, Zeraati F, Mohammadi M, Haddadi R Pharmacol Res Perspect. 2024; 12(2):e1188.

PMID: 38483045 PMC: 10938791. DOI: 10.1002/prp2.1188.

Anticataleptic activity of nicotine in rats: involvement of the lateral entorhinal cortex.

Ionov I, Pushinskaya I, Gorev N, Frenkel D, Severtsev N Psychopharmacology (Berl). 2021; 238(9):2471-2483.

PMID: 34002247 DOI: 10.1007/s00213-021-05870-3.

Neurorestorative effects of sub-chronic administration of ambroxol in rodent model of Parkinson's disease.

Mishra A, Krishnamurthy S Naunyn Schmiedebergs Arch Pharmacol. 2019; 393(3):429-444.

PMID: 31654086 DOI: 10.1007/s00210-019-01737-9.

Metal Chelation Therapy and Parkinson's Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs.

Tosato M, Di Marco V Biomolecules. 2019; 9(7).

PMID: 31324037 PMC: 6681387. DOI: 10.3390/biom9070269.

References

Connolly B, Lang A . Pharmacological treatment of Parkinson disease: a review. JAMA. 2014; 311(16):1670-83. DOI: 10.1001/jama.2014.3654. View

Raha S, Robinson B . Mitochondria, oxygen free radicals, and apoptosis. Am J Med Genet. 2001; 106(1):62-70. DOI: 10.1002/ajmg.1398. View

Taylor J, Main B, Crack P . Neuroinflammation and oxidative stress: co-conspirators in the pathology of Parkinson's disease. Neurochem Int. 2013; 62(5):803-19. DOI: 10.1016/j.neuint.2012.12.016. View

Closa D, Folch-Puy E . Oxygen free radicals and the systemic inflammatory response. IUBMB Life. 2004; 56(4):185-91. DOI: 10.1080/15216540410001701642. View

Fabbrini G, Brotchie J, Grandas F, Nomoto M, Goetz C . Levodopa-induced dyskinesias. Mov Disord. 2007; 22(10):1379-1389. DOI: 10.1002/mds.21475. View

Haddadi R, Nayebi A, Farajniya S, Brooshghalan S, Sharifi H . Silymarin improved 6-OHDA-induced motor impairment in hemi-parkisonian rats: behavioral and molecular study. Daru. 2014; 22:38. PMC: 4001109. DOI: 10.1186/2008-2231-22-38. View

Bartels A, Leenders K . Neuroinflammation in the pathophysiology of Parkinson's disease: evidence from animal models to human in vivo studies with [11C]-PK11195 PET. Mov Disord. 2007; 22(13):1852-6. DOI: 10.1002/mds.21552. View

Nieder C, Andratschke N, Wiedenmann N, Molls M . Prevention of radiation-induced central nervous system toxicity: a role for amifostine?. Anticancer Res. 2005; 24(6):3803-9. View

Kakkar P, Das B, Viswanathan P . A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys. 1984; 21(2):130-2. View

10.

Haddadi R, Brooshghalan S, Farajniya S, Nayebi A, Sharifi H . Short-Term Treatment with Silymarin Improved 6-OHDA-Induced Catalepsy and Motor Imbalance in Hemi-Parkisonian Rats. Adv Pharm Bull. 2016; 5(4):463-9. PMC: 4729352. DOI: 10.15171/apb.2015.063. View

11.

Murley J, Nantajit D, Baker K, Kataoka Y, Li J, Grdina D . Maintenance of manganese superoxide dismutase (SOD2)-mediated delayed radioprotection induced by repeated administration of the free thiol form of amifostine. Radiat Res. 2008; 169(5):495-505. PMC: 2384167. DOI: 10.1667/RR1194.1. View

12.

Shadrina M, Slominsky P, Limborska S . Molecular mechanisms of pathogenesis of Parkinson's disease. Int Rev Cell Mol Biol. 2010; 281:229-66. DOI: 10.1016/S1937-6448(10)81006-8. View

13.

Tatton W, Chalmers-Redman R, Brown D, Tatton N . Apoptosis in Parkinson's disease: signals for neuronal degradation. Ann Neurol. 2003; 53 Suppl 3:S61-70; discussion S70-2. DOI: 10.1002/ana.10489. View

14.

Tufekci K, Meuwissen R, Genc S, Genc K . Inflammation in Parkinson's disease. Adv Protein Chem Struct Biol. 2012; 88:69-132. DOI: 10.1016/B978-0-12-398314-5.00004-0. View

15.

Kouvaris J, Kouloulias V, Vlahos L . Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist. 2007; 12(6):738-47. DOI: 10.1634/theoncologist.12-6-738. View

16.

Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S . The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011; 1813(5):878-88. DOI: 10.1016/j.bbamcr.2011.01.034. View

17.

Gilgun-Sherki Y, Melamed E, Offen D . Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology. 2001; 40(8):959-75. DOI: 10.1016/s0028-3908(01)00019-3. View

18.

Calabresi P, Di Filippo M, Ghiglieri V, Picconi B . Molecular mechanisms underlying levodopa-induced dyskinesia. Mov Disord. 2008; 23 Suppl 3:S570-9. DOI: 10.1002/mds.22019. View

19.

Chronidou F, Apostolakis E, Papapostolou I, Grintzalis K, Georgiou C, Koletsis E . Beneficial effect of the oxygen free radical scavenger amifostine (WR-2721) on spinal cord ischemia/reperfusion injury in rabbits. J Cardiothorac Surg. 2009; 4:50. PMC: 2751753. DOI: 10.1186/1749-8090-4-50. View

20.

Haddadi R, Nayebi A, Brooshghalan S . Pre-treatment with silymarin reduces brain myeloperoxidase activity and inflammatory cytokines in 6-OHDA hemi-parkinsonian rats. Neurosci Lett. 2013; 555:106-11. DOI: 10.1016/j.neulet.2013.09.022. View