Carbimazole Drug-Induced Hepatitis during Treatment of Graves’ Disease: About Four Cases at Dakar Teaching Hospital

Introduction: Mostly reported common side effects of carbimazole are cutaneous allergies and severe agranulocytosis. However, hepatotoxicity is rarely described. Thus, we report four observations of carbimazole drug-induced hepatitis during the treatment of Graves’ disease, which imputability is likely and probably an immuno-allergic mechanism. Observations: They were four women whose average age was 43 years, with extreme ages of 32 and 54. Patients were monitored and treated with carbimazole in doses contained between 40 mg and 60 mg per day. Clinical manifestations of liver injury were mainly dominated by cholestatic jaundice, found in 100% of our patients. A painful sensitivity of the right hypochondrium was concomitant with jaundice for two patients. The jaundice time to onset after the beginning of treatment with carbimazole varies between 1 month and 6 months. They all had acute hepatitis. The biological assays used to determine the type of liver injury showed, in all cases, a mixed, cholestatic and cytolytic hepatitis. Therapeutically, in all patients, carbimazole was stopped as soon as the suspicion of its incrimination in the occurrence of liver damage was set up. They all had a substitution of carbimazole with benzylthiouracil. Evolution was favorable for all patients, after therapeutic substitution. It was marked by disappearance of jaundice and normalization of the liver biological parameters within a maximum delay of two months after stopping carbimazole use. Conclusion: Treatment with synthetic antithyroid drugs, particularly carbimazole that is most widely used in our regions, requires clinical and biological monitoring. This surveillance, which is often difficult in Africa because of the limited economic resources, can lead to the occurrence of side effects such as potentially serious drug-induced hepatitis, but which has been favorable in our observations.

Impact of ginger aqueous extract on carbimazole induced testicular degenerative alterations and oxidative stress in albino rats

Objective: To evaluate the effect of ginger (Zingiber officinale) aqueous extract, a natural herb, with antioxidant properties, on testicular toxicity and oxidative stress induced by the antithyroid drug carbimazole in albino rats.Methods: Four groups of male albino rats were used. Group I served as control. Group II rats were treated with ginger aqueous extract (24 mg/mL). Group III rats were given orally carbimazole (1.35 mg/kg bw). Group IV rats were given carbimazole and ginger extract. Animals were sacrificed and their testes were removed and stained with H&E for histological examination. Sperms were collected from epididymis for detection of sperm head abnormalities. Immunohistochemical expression of PCNA and Bax was detected in the testes.MDA, CAT and GSH were measured in the sera.Results: Treating rats with carbimazole revealed significant alterations in the tissue of testis including decreased seminiferous epithelium height, decreased diameter of seminiferous tubule and changes in the spermatogenic layers arrangement. Intertubular hemorrhage and congested blood vessels were noted. An increase in sperm head abnormalities was recorded.Decreased cell proliferation was reflected by a decrease in PCNA expression, while the increase in apoptotic rate was accompanied with an increase in Bax expression. Oxidative stress was demonstrated by an increase in malondialdehyde and decrease in activity of catalase and glutathione. Combined treatment of carbimazole and aqueous ginger extract led to an improvement in histological, morphometrical, immunohistochemical changes and oxidative stress induced by carbimazole.Conclusions: The ameliorative effects of ginger extract could be due to its antioxidant properties.

Selenium ameliorates carbimazole induced hepatotoxicity and oxidative stress in Albino rats

Objective:To evaluate the effect of the antithyroid drug,carbimazole on liver of albino rats and the possible ameliorative role of selenium.Methods:Four groups of rats were used(n=10),Group 1 served as normal control,Group 2 was orally given sodium selenite(10μg/kg body weight)daily for 8 weeks,Group 3 was orally given carbimazole at a dose level of 1.35 mg/kg body weight,Group 4 was orally administered carbimazole and sodium selenite daily for 8 weeks.Rats in control and treated groups were sacrificed by cervical decapitation after 8 weeks of treatment,their livers were removed and stained with H&E for histological examinations.Alanine aminotransferase and aspartate aminotransferase were determined in the sera.Malondialdehyde and the antioxidant enzymes,catalase and superoxide dismutase were measured in the liver.Results:Cytoplasmic vacuolation of the hepatocytes,necrosis,leucocytic infiltrations,blood vessels congestion and fatty degeneration were observed in liver of carbimazole-treated animals.Carbimazole caused marked elevation in serum alanine aminotransferase and aspartate aminotransferase.It also caused an increase in malondialdehyde and depletion of the activity of the antioxidant enzymes,catalase and superoxide dismutase in the liver.Treating animals with carbimazole and selenium led to an improvement in both the histological and biochemical alterations induced by carbimazole.Moreover,selenium reduced the level of malondialdehyde and increased the activity of antioxidant enzymes,superoxide dismutase and catalase.Conclusions:It is concluded that the ameliorative effect of selenium against the hepatotoxicity of carbimazole is attributed to its antioxidant properties.