Antinociceptive, anxiolytic, and depression-like effects of hydrogen sulfide, nitric oxide, and carbon monoxide in rats and the role of opioidergic and serotonergic systems in antinociceptive activity

Baskin V., EROĞLU E., Harmanci N., EROL K.

FUNDAMENTAL & CLINICAL PHARMACOLOGY, cilt.36, sa.4, ss.674-686, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 36 Sayı: 4
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1111/fcp.12763
  • Dergi Adı: FUNDAMENTAL & CLINICAL PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, Agricultural & Environmental Science Database, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.674-686
  • Anahtar Kelimeler: anxiety, depression, hydrogen sulfide, nitric oxide, pain, rats, FORCED SWIMMING TEST, ANTIDEPRESSANT-LIKE, SIGNALING MOLECULE, NEUROPATHIC PAIN, NMDA RECEPTORS, L-ARGININE, PLUS-MAZE, INVOLVEMENT, EXPRESSION, MICE
  • Eskişehir Osmangazi Üniversitesi Adresli: Evet

Özet

l-Arginine, a nitric oxide (NO) donor; sodium hydrosulfide (NaHS), a hydrogen sulfide (H2S) donor; and tricarbonyldichlororuthenium(II) dimer (CORM-2), carbon monoxide (CO) donor, are characterized as bioactive gas mediators that have been researched for their roles in human physiology. This study aimed to compare the effects of these mediators on pain, anxiety, and depression. Ninety-one adult male Sprague-Dawley rats were used for the experiments. Locomotor activity, elevated plus maze, forced swimming, tail clip, hot plate, and writhing tests were used for the assessments after the administration of l-arginine (30-100 mg/kg), a NO donor; NaHS (5-10 mg/kg), a H2S donor; and CORM-2 (5-10 mg/kg), CO donor. Intraperitoneal H2S, NO, malondialdehyde (MDA), glutathione (GSH), and tumor necrosis factor-alpha (TNF-alpha) levels were determined by enzyme-linked immunosorbent assay (ELISA). No statistical significance was found in the locomotor activity. NO and CO significantly extended latency at high doses in tail clip test. No significant activity was observed at any dose of all three substances on a hot plate. Both doses of CO and high doses of NO and H2S showed an antinociceptive effect in the writhing test. While the opioidergic system plays a role in the spinal antinociceptive effect of l-arginine, both serotonergic and opioidergic systems play a role in its peripheral antinociceptive effect. The serotonergic system plays a role in the peripheral antinociceptive effect of CORM-2. The time spent in open arm increased significantly in all groups an elevated plus maze. High doses of all three substances significantly increased the duration of immobility in the forced swimming test. No statistical significance was observed in MDA, GSH, and TNF-alpha levels. High doses of NO and CO showed a spinal antinociceptive effect. Both doses of CO and high doses of NO and H2S showed a peripheral antinociceptive effect. All three agents showed anxiolytic and depression-like effects.