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‐α (TNF‐α) 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‐α 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.

Introduction: Nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO) are known as gaseous autocoids. It is not clear how the application of exogenous NO, H2S and CO alters the thiol/disulfide balance and advanced oxidation protein products (AOPPs) in the hippocampus and serum. Materials and Methods: In the study, rats were exogenously injected with L-arginine (100 mg/kg) as a NO donor, NaHS (10 mg/ kg) as a H2S donor, and CORM-2 (10 mg/kg) as a CO donor (II) (a tricarbonyldichlororuthenium dimer). Thiol/disulfide balance and advanced protein oxidation products were analyzed in hippocampus and serum samples. Results: The native thiol level in the hippocampus of the L-arginine group was statistically decreased compared to the native thiol level of the control group (p≤0.0001). The disulfide level in the hippocampus of the L-arginine group was statistically increased compared to the control group (p=0.009). Hippocampal total thiol level of NaHS group and CORM-2 group increased statistically (p=0.008,p=0.0157, respectively), while serum disulfide level of CORM-2 group decreased (p=0.0005). Serum and hippocampus AOPPs levels of the NaHS group were statistically increased compared to the control group (***p=0.0006, **p=0.0047, respectively). Similarly, the hippocampal AOPP level in the CORM-2 group was found to be statistically increased compared to the AOPP level in the control group (p=0.0437). Conclusion: As NaHS can improve thiol/disulfide balance, new studies are needed for CORM-2 and L-Arginine. This study is the first to report the effects of NO, H2S and CO on thiol/disulfide balance and AOPPs in the hippocampus and serum. Keywords: NO, H2S, CO, AOPPs, Thiol/disulfide

The current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in the wholesale market in Wuhan, China in the last months of 2019 and spread to almost all countries in the world. Although there is currently no specific treatment for COVID-19, certain agents are used worldwide, based on in vitro, in vivo studies, and randomized controlled trials. In this review, brief information about these drugs used for the treatment of COVID-19, the results of the conducted studies and the possible adverse effects of the drugs are summarized. We hope that this review will provide an impression of the most current therapeutic drugs used to prevent, control and treat COVID-19 patients until the approval of vaccines and specific drugs targeting SARS-CoV-2. Key Words: COVID-19, SARS CoV-2, pharmacotherapeutics

Objectives:To investigate nonsteroidal anti-inflammatory drugs effectiveness in colorectal distension (CRD)-induced visceral pain model.Materials and Methods:Male Sprague–Dawley (250–300 g) rats were anesthetized with ketamine (50 mg/kg, intraperitoneally [i.p.]) and chlorpromazine (25 mg/kg, i.p.). Two bipolar Teflon-coated Ni/Cr wire electrodes (80-M diameter) were placed in the abdominal external oblique muscle for the recording of electromyography. Jugular vein catheter was placed for the administration of drugs. CRD method was applied to evaluate of visceral pain. All drugs (paracetamol, meloxicam, metamizole, and dexketoprofen) administered intravenously.Results:Paracetamol 200, 400, and 600 mg/kg did not change the visceromotor response (VMR) when compare with the control group. Meloxicam 2 and 4 mg/kg showed no effect but at doses of 6 mg/kg meloxicam significantly ([51.9 ± 6.4%] [P < 0.001]) decreased VMR compared with the control group. Metamizole 200 mg/kg did not change responses but dose of 400 and 600 mg/kg metamizole reduced VMR. Dexketoprofen 2 and 4 mg/kg did not cause a change in VMR but 6 mg/kg dose significantly reduced response compared with the control group ([43.9 ± 3.9%, 36.8 ± 2.8%, 34.8 ± 2.5%, 42.1 ± 4.8%, 40.7 ± 3.5%, 36.4 ± 2.7%, and 26.1 ± 2.2%]; from 10 min to 70 min, respectively, [P < 0.05]).Conclusion:Metamizole, dexketoprofen and meloxicam show antinociceptive effect with different duration of action on CRD-induced visceral pain model. This condition can be explained due to different chemical structures and different mechanisms which play a role in modulation of pain.