Introduction: Hepatic encephalopathy (HE) is a serious clinical problem leading to severe neurological disorders and death. No specific treatment is available for the management of HE-associated neurological damage. This study aimed to evaluate the effect of dextromethorphan (DXM) on oxidative stress and disturbed locomotor activity in an animal model of HE. Material and methods: In the current study, BALB/c mice received acetaminophen (APAP; 1000 mg/kg, intraperitoneally [IP]). Dextromethorphan (0.5, 1, 5, 10 mg/kg, subcutaneously [SC]) was injected in three doses (every 6 h), starting two hours after acetaminophen. Animals' locomotor activity, brain and plasma ammonia levels, as well as biomarkers of oxidative stress and inflammatory cytokines in the brain tissue, were assessed 24 hours after acetaminophen injection. Results: It was found that APAP administration was significantly associated with liver damage and increased plasma biomarkers of liver injury. Ammonia levels in plasma and brain tissue of APAP-treated mice also increased significantly. There was also a significant difference in motor activity between the control and APAP-treated animals. The acute liver injury also increased the brain level of pro-inflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin 6 [IL-6], and interleukin 1β ). It was found that DXM could significantly improve the motor activity of animals in all doses and decrease the biomarkers of inflammation and oxidative stress in the brain tissue of animals with hyperammonemia. Conclusions: The effect of dextromethorphan on oxidative stress and inflammation seems to be a major mechanism for its neuroprotective properties in HE. Based on these data DXM could be applied as an effective pharmacological option against HE-associated brain injury.

Aim of the study: Cholestasis/cirrhosis could induce erythrocyte lysis. The incidence of various types of anemia in cirrhosis is approx. 75%. Several studies have mentioned the pivotal role of oxidative stress in this complication. Taurine (TAU) is the human body's most abundant free amino acid. TAU is known as a robust cell membrane stabilizer. Many studies have mentioned that TAU could counteract oxidative stress in various experimental models. The current study was intended to evaluate the effect of TAU on erythrocytes in cirrhotic rats. Material and methods: Bile duct ligation (BDL) surgery was carried out on rats. Then, complete blood count (CBC), hemoglobin (Hgb), hematocrit (HTC), and erythrocytes' G6PD, catalase (CAT), and superoxide dismutase (SOD) activity were measured. Moreover, biomarkers of oxidative stress were assessed, and the erythrocytes' morphological changes were monitored in the cirrhotic mice exposed to TAU (0.25%, 0.5%, and 1% w : v in drinking water). Results: Significant changes in the assessed erythrocyte parameters (G6PD activity, Hgb, HTC, and erythrocyte count) and red blood cells (RBC) morphological alterations were detected on day 42 after BDL surgery. Biomarkers of oxidative stress also did not change at the time points, except on post-BDL days 28 and 42. A significant decrease in blood parameters was evident at post-BDL day 42. All doses of TAU (0.25%, 0.5%, and 1% w : v in drinking water) significantly improved erythrocyte parameters and encountered oxidative stress in the erythrocytes of cirrhotic animals. Conclusions: These data indicate that TAU could be a safe agent to mitigate cirrhosis-induced erythrocyte damage and anemia. Further investigations are necessary to prove this in clinical settings.

Ammonium ion (NH4+) is the major suspected molecule responsible for neurological complications of hepatic encephalopathy (HE). No specific pharmacological action for NH4+‐induced brain injury exists so far. Excitotoxicity is a well‐known phenomenon in the brain of hyperammonemic cases. The hyperactivation of the N‐Methyl‐ d‐aspartate (NMDA) receptors by agents such as glutamate, an NH4+ metabolite, could cause excitotoxicity. Excitotoxicity is connected with events such as oxidative stress and neuroinflammation. Hence, utilizing NMDA receptor antagonists could prevent neurological complications of NH4+ neurotoxicity. In the current study, C57BL6/J mice received acetaminophen (APAP; 800 mg/kg, i.p) to induce HE. Hyperammonemic animals were treated with ketamine (0.25, 0.5, and 1 mg/kg, s.c) as an NMDA receptor antagonist. Animals' brain and plasma levels of NH4+ were dramatically high, and animals' locomotor activities were disturbed. Moreover, several markers of oxidative stress were significantly increased in the brain. A significant increase in brain tissue levels of TNF‐α, IL‐6, and IL‐1β was also detected in hyperammonemic animals. It was found that ketamine significantly normalized animals' locomotor activity, improved biomarkers of oxidative stress, and decreased proinflammatory cytokines. The effects of ketamine on oxidative stress biomarkers and inflammation seem to play a key role in its neuroprotective mechanisms in the current study.