ABSTRACT
This study aimed to investigate the protective effect of selenium (Se) on methimazole (MMI; an antithyroid drug)-induced hepatotoxicity in adult rats and their progeny. Female Wistar rats were randomly divided into four groups of six rats in each group: group I served as controls that received standard diet; group II received MMI in drinking water as 250 mg L(-1) and standard diet; group III received both MMI (250 mg L(-1), orally) and Se (0.5 mg kg(-1) of diet); group IV received Se (0.5 mg kg(-1) of diet) as sodium selenite. Treatments were started from the 14th day of pregnancy until day 14 after delivery. Exposure of rats to MMI promoted oxidative stress with an increase in liver malondialdehyde levels, advanced oxidation protein products and protein carbonyl contents and a decrease in the levels of glutathione, nonprotein thiols and vitamin C. A decrease in the activities of liver glutathione peroxidase, superoxide dismutase, catalase and lactate dehydrogenase and in the levels of plasma total protein and albumin was also observed. Plasma transaminase activities and total, direct and indirect bilirubin levels increased. Coadministration of Se through diet improved all biochemical parameters. The histopathological changes confirmed the biochemical results. Therefore, our investigation revealed that Se, a trace element with antioxidant properties, was effective in preventing MMI-induced liver damage.
Subject(s)
Antithyroid Agents/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , Methimazole/toxicity , Oxidative Stress/drug effects , Sodium Selenite/pharmacology , Animals , Female , Lipid Peroxidation/drug effects , Liver/chemistry , Liver/drug effects , Malondialdehyde/analysis , Methimazole/antagonists & inhibitors , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/drug therapy , Rats , Rats, WistarABSTRACT
We report a 12-year-old girl with hyperthyreosis who presented methamazole-induced toxic epidermal necrolysis (TEN). The patient's past history suggests a presence of autoimmune disease. To our knowledge it is the first report describing such an adverse effect of methimazole.
Subject(s)
Methimazole/poisoning , Stevens-Johnson Syndrome/drug therapy , Antithyroid Agents/therapeutic use , Autoimmune Diseases , Child , Female , Humans , Hyperthyroidism , Methimazole/antagonists & inhibitors , Methimazole/therapeutic use , PolandABSTRACT
Intraperitoneal administration of mercaptomethylimidazole (methimazole), a potent antithyroid drug belonging to the thionamide group, caused a significant increase in gastric secretion both in control and pylorus-ligated mice. The drug also induced significant stimulation of gastric acid and pepsinogen secretion in both the animal systems studied. The dose-response curve indicated a nearly 10-fold increase in acid output by injection of 0.55 mg mercaptomethylimidazole per 25 g body weight. The duration profile of the drug response at the dose mentioned showed acid secretion almost at a linear rate up to 2.5 hr, after which the response decreased to some extent. Of the other antithyroid drugs of the same family, only thiourea activated acid secretion but the response was much smaller than mercaptomethylimidazole. Histamine, one of the physiological secretagogues of gastric acid secretion, was found to be less active than mercaptomethylimidazole. Mercaptomethylimidazole-induced stimulation of acid secretion could be effectively blocked by prior administration of cimetidine and completely by omeprazole and not by atropine. Verapamil and nifedipine had also some inhibitory effect. These observations indicate that mercaptomethylimidazole stimulates HCl secretion through the involvement of H2-receptor and through the functioning of the H+-K+-ATPase of the parietal cells. The bulk movement of water during increased HCl secretion was partially sensitive to cimetidine and omeprazole and was also associated with an increased secretion of Na+ and K+ in the gastric juice. This indicates that mercaptomethylimidazole also induced water transport through a separate mechanism.
Subject(s)
Gastric Acid/metabolism , Methimazole/pharmacology , Receptors, Histamine H2/drug effects , Animals , Cimetidine/pharmacology , Male , Methimazole/antagonists & inhibitors , Mice , Mice, Inbred BALB C , Nifedipine/pharmacology , Omeprazole/pharmacology , Parietal Cells, Gastric/drug effects , Potassium/metabolism , Proton-Translocating ATPases/metabolism , Pylorus/drug effects , Receptors, Histamine H2/physiology , Sodium/metabolism , Verapamil/pharmacologyABSTRACT
The influence of anionic groups on interaction of nucleophilic sulfur compounds with the purified hog liver flavin-containing monooxygenase was evaluated from kinetic constants obtained with various dithiobenzoates, thiolbenzoates, and thiolalkylcarboxylic acids. All compounds tested bearing a single negative charge localized on sulfur were excellent substrates but derivatives with a carboxylic acid group one or two carbons removed from the heteroatom exhibited low or no substrate activity. The effect of a carboxylic acid group more distal from sulfur appeared to depend on steric factors that are not well defined. For instance, none of the carboxylic acids (C2-C8) bearing a single thiol on the terminal carbon were oxygenated at detectable rates, whereas dihydrolipoic acid appeared to be a substrate although the concentration required for half-maximal activity was quite high (approximately 2 mM). Lipoic acid was a much better substrate (Km = 0.12 mM), and kinetic constants obtained with lipoic acid analogues suggest that position of the negative charge relative to the dithiolane ring is critical, since increasing the length of the side chain increased the Km. None of the alicyclic disulfides or sulfides containing one or more carboxylic acid groups showed detectable substrate activity. However, the more lipophilic sulfur-containing fatty acids inhibited the enzyme which may mask their potential substrate activity.
