Mitigation of Acute Hepatotoxicity Induced by Cadmium Through Morin: Modulation of Oxidative and Pro-apoptotic Endoplasmic Reticulum Stress and Inflammatory Responses in Rats.

Cadmium (Cd) is a toxic heavy metal with significant environmental health hazards. It enters the body through various routes with tissue accumulation. The relatively longer half-life with slow body clearance significantly results in hepatotoxicity during its liver detoxification. Therefore, researchers are exploring the potential use of herbal-derived phytocomponents to mitigate their toxicity. Here, we investigated, for the first time, the possible ameliorative effect of the phytochemical Morin (3,5,7,29,49-pentahydroxyflavone) against acute Cd-induced hepatotoxicity while resolving its underlying cellular mechanisms in a rat animal model. The study involved 50 adult male Sprague-Dawley rats weighing 200-250 g. The animals were divided into five equal groups: control, Cd, Morin100 + Cd, Morin200 + Cd, and Morin200. The 2nd, 3rd, and 4th groups were intraperitoneally treated with Cd (6.5 mg/kg), while the 3rd, 4th, and 5th groups were orally treated with Morin (100 and 200 mg/kg) for 5 consecutive days. On the 6th day, hepatic function (serum ALT, AST, ALP, LDH enzyme activities, and total bilirubin level) testing, transcriptome analysis, and immunohistochemistry were performed to elucidate the ameliorative effect of Morin on hepatotoxicity. In addition to restoring liver function and tissue injury, Morin alleviated Cd-induced hepatic oxidative/endoplasmic reticulum stress in a dose-dependent manner, as revealed by upregulating the expression of antioxidants (SOD, GSH, Gpx, CAT, and Nrf2) and decreasing the expression of ER stress markers. The expression of the proinflammatory mediators (TNF-α, IL-1-ß, and IL-6) was also downregulated while improving the anti-inflammatory (IL-10 and IL-4) expression levels. Morin further slowed the apoptotic cascades by deregulating the expression of pro-apoptotic Bax and Caspase 12 markers concomitant with an increase in anti-apoptotic Blc2 mRNA expression. Furthermore, Morin restored Cd-induced tissue damage and markedly suppressed the cytoplasmic expression of JNK and p-PERK immunostained proteins. This study demonstrated the dose-dependent antioxidant hepatoprotective effect of Morin against acute hepatic Cd intoxication. This effect is likely linked with the modulation of upstream p-GRP78/PERK/ATF6 pro-apoptotic oxidative/ER stress and the downstream JNK/BAX/caspase 12 apoptotic signaling pathways.

Which is good for pre-operative anxiety? Midazolam, video games or teaching with cartoons: A randomised trial.

BACKGROUND: Pre-operative anxiety in children has been associated with adverse clinical outcomes such as difficulty in anaesthesia induction, emergence delirium and negative postoperative behavioural changes. Therefore, pre-operative anxiety should be alleviated in both children and clinicians. OBJECTIVE: We investigated the effect on pre-operative anxiety of premedication with midazolam, playing video games or watching a cartoon about anaesthesia. DESIGN: A prospective randomised trial. SETTING: Single-centre study performed between August 2018 and June 2019. PATIENTS: We enrolled 138 patients aged 5 to 8 years undergoing elective surgery. INTERVENTIONS: After evaluating baseline (T0) anxiety levels using the modified Yale Pre-operative Anxiety Scale (mYPAS) in the pre-operative holding area, 0.5 mg kg-1 oral midazolam was given to Group M, a tablet with videogame applications was given to Group T, and Group S watched the cartoon 'Süko Is Being Operated'. mYPAS values were recorded a further three times: 20 min after the intervention (T1), while entering the operating room (T2), and during mask induction of anaesthesia (T3). MAIN OUTCOME MEASURES: The primary endpoint was the change in children's anxiety levels from baseline. The secondary endpoint was cooperation during mask induction. RESULTS: The baseline mYPAS scores were comparable (40.7, 42.6 and 40.7 in groups M, S and T respectively). The mean mYPAS scores at T1 were 32.6, 34.7, 26.8 and at T2 were 38.6, 42.7, 35 in groups M, S and T, respectively. There were significant differences between groups S and T at T1 and T2 (P < 0.001, P = 0.010). A significant decrease was found in Group T compared with both groups M and S from T0 to T1 (P = 0.002). mYPAS values at T3 were 38.3, 43.7, 39.5 in groups M, S and T, respectively, with no difference between the groups (P = 0.224). Mask acceptance scores were similar in all groups (P = 0.912). CONCLUSIONS: The passive teaching technique of watching a video for reducing anxiety levels was not effective. However, active distraction with videogames was found to be a valuable method to reduce pre-operative anxiety. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03530670.