Protectif effects of anandamide aganist cisplatin- induced peripheral neuropathy in rats.


Çengelli Ünel Ç., Aydın Ş., Ulupınar E., Özatik O. , Kaygısız B., Yıldırım E.

Turkish Journal Of Medical Sciences, vol.0, no.0, 2021 (Journal Indexed in SCI Expanded)

  • Publication Type: Article / Article
  • Volume: 0 Issue: 0
  • Publication Date: 2021
  • Doi Number: 10.3906/sag-2103-240
  • Title of Journal : Turkish Journal Of Medical Sciences

Abstract

Background/aim: Cisplatin (CIS) is an effective antineoplastic agent used in treatment of several cancer types. Peripheral neuropathy is a major dose-limiting side-effect in cisplatin therapy. Cannabinoids may alleviate this painful side effect. This study investigated the  analgesic effects of anandamide (AN) on CIS-induced peripheral neuropathy, in vitro effects of AN in CIS neurotoxicity and influence of nitric oxide (NO) in this effect.  Materials and methods: This is an experimental animal study. Primary DRG cultures were prepared from one day old rats for in vitro investigations. DRG cells were incubated with CIS (100-300 mM), and AN (10, 50, 100 and 500 μM) was administered with the submaximal concentration of CIS. Female Sprague Dawley rats were divided into Control, CIS, CIS+AN, CIS+AN+ L-NG-nitro arginine methyl ester (L-NAME). CIS was administered 3 mg/kg ip once weekly for five weeks. AN (1 mg/kg ip) or in combination with 10 mg/kg ip L-NAME was administrated 30 min before CIS injection. Mechanical allodynia, thermal hyperalgesia and tail clip tests were performed. After intracardiac perfusion, sciatic nerves (SN) and dorsal root ganglia (DRG) were isolated and semi-thin sections were stained with toluidine blue and investigated histologically. SPSS 21.0 and Sigma STAT 3.5 were used for statistical analysis. One/two way ANOVA, Kruskal Wallis, and Wicoxon Signed Ranks tests were used. A p-value of 0.05 was accepted as significant. Results: Cisplatin caused significant mechanical allodynia. AN and AN+L-NAME significantly increased hind paw withdrawal latency in mechanical allodynia test. The degenerated axons significantly increased in cisplatin group, anandamide decreased this effect. The frequency of larger neurons seems to be higher in CIS+AN group. Conclusion: Anandamide may be a therapeutic alternative for the treatment of cisplatin25 induced peripheral neuropathy, however its central adverse effects must be considered.