Mechanisms of muscular electrophysiological and mitochondrial dysfunction following exposure to malathion, an organophosphorus pesticide

Muscle dysfunction in acute organophosphorus (OP) poisoning is a cause of death in human. The present study was conducted to identify the mechanism of action of OP in terms of muscle mitochondrial dysfunction. Electromyography (EMG) was conducted on rats exposed to the acute oral dose of malathion (400 mg/kg) that could inhibit acetylcholinesterase activity up to 70%. The function of mitochondrial respiratory chain and the rate of production of reactive oxygen species (ROS) from intact mitochondria were measured. The bioenergetic pathways were studied by measurement of adenosine triphosphate (ATP), lactate, and glycogen. To identify mitochondrial-dependent apoptotic pathways, the messenger RNA (mRNA) expression of bax and bcl-2, protein expression of caspase-9, mitochondrial cytochrome c release, and DNA damage were measured. The EMG confirmed muscle weakness. The reduction in activity of mitochondrial complexes and muscular glycogen with an elevation of lactate was in association with impairment of cellular respiration. The reduction in mitochondrial proapoptotic stimuli is indicative of autophagic process inducing cytoprotective effects in the early stage of stress. Downregulation of apoptotic signaling may be due to reduction in ATP and ROS, and genotoxic potential of malathion. The maintenance of mitochondrial integrity by means of artificial electron donors and increasing exogenous ATP might prevent toxicity of OPs

The correlation between blood oxidative stress and sialic acid content in diabetic patients with nephropathy, hypertension, and hyperlipidemia

This clinical study was designed to find out the correlation between oxidative stress and sialic acid (SA) content of plasma and RBCs in patients with type 2 diabetes. We evaluated SA concentration and oxidative stress biomarkers in healthy subjects and diabetic patients with and without complications in a cross-sectional survey. Significant changes in oxidative stress biomarkers and RBC-SA were revealed in the diabetic patients compared to those in the healthy group. Plasma SA significantly increased with an increase in lipid peroxidation of RBCs (LPO-RBC) (P < 0.001) in the diabetic patients without complication. RBC-SA significantly decreased with an elevation in LPO-RBC (P < 0.001) in all the diabetic patients and those with nephropathy. There was no significant correlation between plasma and RBC-SA and other oxidative stress biomarkers in the diabetic subjects. In multiple logistic regression analysis, RBC-SA was independently related to LPO-RBC in all the diabetic patients and those with nephropathy. We conclude that the induction of LPO-RBC in diabetic patients and those with nephropathy may influence the SA decomposition of RBC membrane, thereby altering its functions and transporter activities. Therefore, LPO-RBC and SA levels in RBCs can be used for prediction of diabetic nephropathy, and further studies to evaluate other factors contributing to desialylation of RBC membrane are justified. © 2019, The Japan Diabetes Society

Sub-acute exposure to benzene accelerates the aging process of red blood cells; an in vivo study

Background: The well-known toxic effects of benzene toxicity are bone marrow depression, reduction in blood cell counts, and induction of leukemia and aplastic anemia. This study was designed to evaluate biomarkers of aging in red blood cells (RBCs). Methods: Mice were exposed to benzene (50, 100, and 200 mg/kg/day) orally for 28 days. A group of benzene-exposed mice were injected intraperitoneally with N-acetylcysteine (NAC, 150 mg/kg/day). Hematological factors, erythrocyte morphology, and sialic acid content of RBCs along with oxidative stress biomarkers were investigated. Results: Benzene dose-dependently reduced RBCs count, hemoglobin level, RBCs membrane sialic acid levels, the total antioxidant capacity of plasma, and G6PD activity of RBCs. The activity of antioxidant enzymes and lactate dehydrogenase, oxidative damage end-products and bilirubin levels, reticulocyte count, and RDW and MCV ranges increased in a dose-dependent manner. Poikilocytosis (spherocyte, burr cell, schistocyte and blister cell) and anisocytosis were observed in high doses of benzene. Conclusion: Our results support the acceleration of RBCs aging and hemolytic anemia in mice exposed to benzene. Co-administration of NAC as an antioxidant effectively alleviated hematotoxicity of benzene. © 2020, Iranian Pediatric Hematology and Oncology Society. All rights reserved

Successful treatment of aluminium phosphide poisoning by dihydroxyacetone: A two-case report study

What is known and objective: Aluminium phosphide (AlP) is an agricultural fumigant which produces phosphine gas in the presence of moisture. Phosphine inhibits oxidative phosphorylation and causes cell death by inhibiting cytochrome C oxidase. Clinical manifestations of AlP poisoning are refractory hypotension, tachycardia, low oxygen saturation and severe metabolic acidosis. Case summary: Two cases received dihydroxyacetone (DHA) in addition to routine management of AlP poisoning. Administration of DHA (7 gr in 50 mL sodium bicarbonate, gavage) 2 times at a 1-hour interval improved the clinical signs. What is new and conclusion: This is the first case report to highlight the safe and successful treatment of AlP poisoning with DHA. However, more clinical studies are recommended to determine the precise mechanism of DHA action. © 2020 John Wiley & Sons Lt