Electrocardiogram Abnormality in Poisoned Patients with Tricyclic Antidepressant.

Background: A wide variety of electrocardiogram (ECG) changes can manifest with antidepressant drugs, occurring at both therapeutic doses and toxic levels. Notably, ECG abnormalities like wide QRS and QT prolongation may be observed in poisoned patients with tricyclic antidepressants (TCAs), indicating severe conditions that necessitate the implementation of cardiac monitoring systems. This study aimed to investigate ECG Abnormality in poisoned patients with tricyclic antidepressants. Methods: This retrospective patient record study was conducted at Razi Hospital in Ahvaz, Iran, from 2006 to 2009. Patient information was extracted from hospital medical records after the established protocol. The chi-square test was employed for initial analysis; subsequently, logistic regression was applied to identify risk factors associated with abnormal ECG findings. We analyzed the data using SPSS (Version 19; IBM) statistical software. P < 0.05 was defined as statistically significant. Results: Among the 210 poisoned patients, comprising 88 men (41.9%) and 122 women (58.1%), the majority fell within the age range of 15 to 25 years. In our study, the most commonly ingested drugs by poisoned patients were amitriptyline in 134 patients (63.8%) and nortriptyline in 42 patients (20%). A significant portion of 137 patients (65.2%) exhibited poisoning symptoms within ˂ 6 hours, while 73 patients (34.8%) showed symptoms between 6 and 24 hours. Our findings indicated that the initial symptoms in poisoned patients included a decreased level of consciousness in 168 patients (80%), nausea and vomiting in 20 patients (9.5%), and various other symptoms. Notably, our results revealed ECG changes in 70 patients, with 32 patients (15.2%) showing a QRS widening (> 0.1sec), 5 patients (2.4%) displaying a tall R wave in aVR, 5 patients (2.4%) exhibiting right axis deviation, and other observed changes. Conclusion: QRS widening in poisoned patients with tricyclic antidepressants is more frequently observed in symptomatic patients, highlighting the importance of ECG screening in these patients.

Metformin in contrast to berberine reversed arsenic-induced oxidative stress in mitochondria from rat pancreas probably via Sirt3-dependent pathway.

Exposure to arsenic has been linked to the development of type 2 diabetes though its mechanism of toxicity remains unresolved. In this study berberine (BBR) effects on arsenic-induced sirtuin 3 (Sirt3) modifications in isolated mitochondria from rat pancreas were evaluated and compared with metformin (MET). With arsenic, mitochondrial reactive oxygen species (ROS), oxidative stress, and insulin resistance were obtained higher than control. From our results and in the presence of arsenic trioxide, insulin resistance and Sirt3 levels were found to be predominantly elevated that could be the result of compensating mechanisms. Apparently, BBR and MET recruit both direct (as an antioxidant) and indirect mechanisms (Sirt3 content) to deal with arsenic trioxide toxicity. Metformin compared with BBR exhibited a less significant effect on ROS levels and since its direct antioxidant property is minor, depressed the ROS level mainly through the Sirt3 modification.

SirT3 regulates diabetogenic effects caused by arsenic: An implication for mitochondrial complex II modification.

BACKGROUND: A large body of evidence indicates that accumulation of oxidative stress originated from impaired mitochondrial respiratory chain is the main cause for the development of numerous diseases including diabetes and cancer. Arsenic exposure is a potential risk factor for type 2 diabetes development which, by disrupting mitochondrial respiration and SirT3 enzyme activity, enhances reactive oxygen species (ROS) level and evokes oxidative stress. In this study the impact of arsenic exposure on the mitochondrial function and SirT3 from rat's liver were examined in the presence or absence of metformin and berberine. METHODS: Serum glucose and insulin levels were assessed in rats exposed to the diabetogenic concentration of arsenic. Isolated hepatocytes and mitochondria were then further evaluated to determine any deleterious consequences. RESULTS: Diabetogenesis triggered by arsenic contributed to the mitochondrial ROS overproduction, impaired complex II activity, glucose homeostasis, glucose tolerance and insulin sensitivity. An increased SirT3 level indicated the compensatory mechanism to deal with this condition. Protective effect of metformin and berberine against these toxic insults were found to be associated with the mitochondrial SirT3 pathway. This pathway through the regulation of mitochondria-associated ROS production and glucose homeostasis in the liver may play a crucial role against the diabetogenic effect of arsenic.

Role of berberine against arsenic induced oxidative damage in isolated rat liver mitochondria.

The aim of the present study was to assess the protective role of berberine against toxicity induced by arsenic in mitochondria from liver of rat. The level of reactive oxygen species and mitochondrial membrane potential changes were evaluated spectrofluorometrically. 20, 40 and 100 µM arsenic concentration increased ROS level approximately by 13.5, 21.3 and 29 %. However, when pretreated mitochondria with berberine (10, 25, 50 µM) were exposed to arsenic (20, 40 and 100 µM), ROS production diminished. Also, for all arsenic concentration mitochondrial membrane damage was detected to be 2.5, 4.8 and 7.26 % respectively. Pretreatment with berberine even at highest concentration (50µM) was not able to retain membrane potential as compared to control. These results showed that mitochondria were significantly affected when exposed to arsenic, forcedly directed toward excess ROS production and mitochondrial membrane disruption. Pretreatment with berberine, reduced ROS generation but did not restore mitochondrial membrane integrity.