Document Type : Research Paper
Authors
1
Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
2
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
3
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Ahl Al Bayt, Karbala, Iraq
4
Department of Internal Medicine and Medical Specialties,"Sapienza" University of Rome, Rome, Italy
5
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
6
Department of Soil Science, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran
7
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
8
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
10.22034/ijps.2021.137302.1728
Abstract
Background: Lithium (Li) is considered the first-choice treatment for bipolar disorder and has a narrow therapeutic index therefore small increase in dose or plasma level can cause toxic effects. Gastrointestinal (GI) decontamination can be regarded as a first-line therapy for acute Li poisoning. Montmorillonite (MMT) is one of the best-known examples of a nanoclay that possesses unique properties for adsorbing substances, especially metals. We investigated the effects of MMT against acute Li intoxication.
Methods: A single dose of Li (10 mEq/kg) was administered to the rats orally followed by oral gavage of MMT suspensions (0.5 or 1.0 g/kg) or activated charcoal (AC) (1g/kg) 5 min later. The serum Li concentration was measured at different times after treatment. Indeed, the serum level of sodium and potassium, WBC count, activity score, electrocardiogram, brain pathology changes as well as pharmacokinetic parameters of Li were evaluated.
Results: MMT at higher doses decreased the Area under the curve (AUC), the elimination rate constant (Ka), the relative bioavailability (F), and increased the clearance of Li (P<0.05). MMT prevented Li induced leukocytosis, at first sampling time, (P<0.05). It also exerted significant cardio protection, restored Li-induced ECG changes, heart rate alterations (P<0.001) and prevented Li induced hypoactivity. A similar amount of serum sodium and potassium concentration were observed in the animals.
Conclusion: These results indicated that not only did MMT reduce the absorption of Li but slao possibly increase its clearance. Therefore, MMT may be a good candidate for decontamination, especially substances that are not well adsorbed by AC.
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