Possible protective role of L-thyroxin on the parotid gland of adult male albino rat in carbimazole induced hypothyroidism: histological, histomorphometry, and ultrastructural study.

BACKGROUND: Thyroid disorders are among the most common metabolic disorders worldwide. Thyroid dysfunction affects salivary glands function, causing hyposalivation. It also provokes physiological and histological changes in parotid, submandibular, and in particular the sublingual gland. THE AIM OF THIS WORK: The aim of this work was to clarify the histological and ultrastructural changes that occur in the parotid gland following carbimazole-induced hypothyroidism in adult male albino rats. The study also aims to investigate the possible protective role of L-thyroxin supplementation on the rat parotid glands after long and short duration of hypothyroidism. MATERIAL AND METHODS: Fifty-five adult male albino rats of Sprague Dawley strain; were divided into four groups and eleven subgroups, five rats each. G І received nothing. G П given normal saline orally daily. G Ш (medical Hypothyroidism, short duration - long duration - recovery group) given Carbimazole orally by gastric tube in a dose of 0.05 mg/kg daily for 3,6 successive weeks for group (a, b) and for 6 successive weeks then were left without any medication for another 3 weeks in recovery group c. G IV-b, c (L-Thyroxine supplemented group, short duration-long duration) given Carbimazole orally daily for 3,6 successive weeks then L-thyroxine was given orally in a dose of (10 µg/100 g/B.W) daily for another 3 successive weeks. Animals were sacrificed 24 hours after the last dose of Carbimazole in G III-a, b and 3 weeks after stoppage the drug in G III-c. Animals were sacrificed 24 hours after the last dose of L- Thyroxine in G IV-b, c. The parotid specimens were processed for histopathological examination by light and electron microscopy. The medically induced Hypothyroidism resulted in significant parotid gland damage which was more obvious with longer duration; as follow: a) most of the acini had irregular outlines and were widely separated with narrow lumen and cytoplasmic vacuoles. b) some acinar cells contained ill defined, irregular, pyknotic or hyperchromatic nuclei. c)Vascular changes: dilated and engorged with blood. d) the interlobular and striated ducts appeared disrupted and dilated. e) extravasated blood with cellular infiltration were seen in the interstitial space. IN CONCLUSION: Thyroid hormones (THs) had a significant effect in protection of parotid gland against damage induced by carbimazole, as it preserved the normal histological architecture of the parotid gland. This beneficial effect of THs was mostly related to its antioxidant properties. The expression of BCL-2 has certain regularity in apoptosis after drug administration. Regulation of glandular atrophy and apoptosis are closely related. The molecular mechanism of the apoptosis of the gland is not clear, and further study is needed in the future.

Toxicological considerations for antithyroid drugs in children.

INTRODUCTION: Propylthiouracil (PTU), methimazole (MMI) and carbimazole are indicated for the treatment of hyperthyroidism in adult and pediatric patients. The aim of this review is to present all the relevant information regarding the use of antithyroid drugs (ATD) in pediatric thyrotoxic cases, the pediatric toxicology of ATD and the warning which has recently been issued for PTU by the FDA. AREAS COVERED: Epidemiology, diagnosis and treatment of pediatric thyrotoxicosis are all presented in this article. The authors also extensively discuss the details regarding the pharmacology, bioactivation, biodisposition, bioavailability and pharmacokinetic properties of the two main ATD (MMI and PTU). EXPERT OPINION: The FDA recently reported that use of PTU is associated with a higher risk for clinically serious or fatal liver injury compared to MMI in both adult and pediatric patients. They also found that congenital malformations were reported approximately three times more often with prenatal exposure to MMI compared with PTU and especially with the use of MMI during the first trimester of pregnancy. The authors believe that PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of MMI, and there are no other treatment options available. That being said, PTU may be the treatment of choice during, and just before, the first trimester of pregnancy.

Effect of selenium on carbimazole-induced testicular damage and oxidative stress in albino rats.

Carbimazole is an antithyroid drug used in treatment of hyperthyroidism. The present investigation studied the effect of carbimazole on testicular activity in albino rats and the ameliorative role of selenium. Treating rats with carbimazole (1.35 mg/kg b.w) daily for 8 weeks caused reduction in the body and testes weight. Moreover, the diameters of the seminiferous tubules and heights of their germinal epithelium were significantly reduced. Testes of treated rats showed many histological alterations included congestion of blood vessels, hemorrhage, degeneration of interstitial tissue and degeneration of spermatogenic cells with apoptosis and necrosis. Histochemical results revealed reduction in polysaccharides, total proteins and nucleic acids contents in testicular tissue. In addition, the level of testosterone, luteinizing hormone (LH), T(3), T(4) and thyroid stimulating hormone (TSH) was significantly decreased in sera of treated animals. Moreover, a high lipid peroxidation with a decrease in the enzymatic antioxidant status, superoxide dismutase (SOD) and catalase (CAT) was recorded in testes homogenate. Treating animals with carbimazole and selenium showed an improvement in the histological structure as well as histochemical components of the testis with an increase in the number of spermatogenic cells. There was an increase in testosterone, LH, T(3), T(4) and TSH levels. Moreover, administration of selenium led to decrease in malondialdehyde and increase in catalase and superoxide dismutase activities. It is suggested that the curative effect of selenium against testicular damage induced by carbimazole may be due to its antioxidant properties.

[A new possible phenotype of carbimazole embryopathy: A case report]. / Un nouveau phénotype possible d'embryopathie au carbimazole : à propos d'une observation.

Many disorders have been described in infants exposed to carbimazole during the first weeks of pregnancy. The most common of them are congenital aplasia cutis, choanal atresia and esophageal atresia. Rather unspecific dysmorphic features and developmental delay have also been reported. This set of congenital malformations suggests the existence of a phenotype of carbimazole embryopathy. To date, about 30 cases have been reported. We report on a new case of pregnancy accidentally conducted under carbimazole which gave birth to a newborn presenting with a hypertrophic pyloric stenosis associated with hiatus hernia and tracheomalacia. These anomalies have been associated with other malformations already identified in children exposed in utero to carbimazole such as scalp defects, retrognathia and gothic palate. As no relation between propylthiouracil and congenital malformations has yet been described, this drug seems highly preferable for pregnant women presenting with hyperthyroidism during the 1st trimester of their pregnancy.

Evaluation of olfactory and auditory system effects of the antihyperthyroid drug carbimazole in the Long-Evans rat.

Carbimazole (2-carbethoxythio-1-methylimidazole) is a thiocarbamide drug used in the treatment of hyperthyroidism in humans. Side effects associated with carbimazole treatment are reported to include impaired taste, impaired olfaction, and hearing loss. The structurally similar antihyperthyroid drug methimazole (1-methyl-2-mercaptoimidazole), also reportedly associated with impaired taste and olfaction in humans, has recently been demonstrated by this laboratory to be an olfactory toxicant by both the oral and intraperitoneal routes of exposure in rodents. A systematic evaluation of sensory system effects of these compounds, either in rodents or humans, is not available in the literature. Male Long-Evans rats were used to evaluate the auditory and olfactory toxicity of carbimazole by two routes of exposure. Histopathological evaluation of nasal cavities from rats administered carbimazole via i.p. and oral routes revealed olfactory mucosal damage and early evidence of repair; a no-observed effect level (NOEL) of 100 mg/kg was observed for orally administered carbimazole. Further, these studies demonstrate evidence for the generation of the olfactory toxic metabolites of carbimazole by the olfactory mucosa itself, as incubation of carbimazole with an olfactory S9 preparation resulted in NADPH-dependent degradation of carbimazole. Evaluation of the auditory startle response in carbimazole-treated rats revealed no deficits, demonstrating that carbimazole does not cause a global loss of hearing in rats.