methimazole and Kidney-Diseases

This study aims to investigate the improving effects of selenium on methimazole-induced kidney impairments in adult rats and their pups. The animals were randomly divided into four groups of six each: group I served as control which received standard diet; group II received only methimazole in drinking water as 250 mg/l; group III received both methimazole (250 mg/l, orally) and selenium (0.5 mg/kg of diet); group IV served as a positive control and received selenium (0.5 mg/kg of diet) as sodium selenite (Na(2)SeO(3)). Treatments were started from the 14th day of pregnancy until day 14 after delivery. In the methimazole-treated group, body and absolute kidney weights decreased in pups and their mothers when compared to control. Daily urine volume, plasma creatinine levels were higher, while urinary levels were lower than in control. Besides, antioxidant enzyme activities, superoxide dismutase, catalase and glutathione peroxidase decreased. Lipid peroxidation recorded an increase revealed by high kidney malondialdehyde levels, while those of plasma and urinary uric acid showed a significant decline. Methimazole-treated rat kidneys exhibited leucocytic infiltrations, vascular congestion and narrowed Bowman's space. Co-administration of selenium through diet improved all the parameters cited above in adult rats and their progeny. Nevertheless, the distorted histoarchitecture in rat kidney was alleviated by selenium treatment. It can then be concluded that selenium is an important protective element that may be used as a dietary supplement against kidney impairments.

Topics: Animals; Animals, Newborn; Antioxidants; Antithyroid Agents; Biomarkers; Body Weight; Female; Kidney; Kidney Diseases; Kidney Function Tests; Lipid Peroxidation; Maternal Exposure; Methimazole; Organ Size; Oxidative Stress; Pregnancy; Rats; Rats, Wistar; Sodium Selenite; Vitamin E

The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 47000 case reports of adverse drug reactions and assigned them to a case group. We also randomly selected 743 cases of adverse drug reactions not associated with leucopenia as a control group. A comparison of patient characteristic data between the two groups using logistic-regression analysis revealed that female sex, autoimmune disease and renal damage were background risk factors for drug-induced leucopenia. In addition, thiamazole, ritodrine, propylthiouracil, ticlopidine, allopurinol, minocycline and captopril administration significantly increased the risk of drug-induced leucopenia. A significant association was also found for fever, chills and pharyngeal abnormalities. Based on these findings, we developed two estimated regression equations to help prevent drug-induced leucopenia in the community pharmacy setting.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Autoimmune Diseases; Case-Control Studies; Child; Databases, Factual; Female; Humans; Kidney Diseases; Leukopenia; Logistic Models; Male; Methimazole; Methotrexate; Middle Aged; Risk Factors; Ritodrine; Sex Factors; Ticlopidine; Young Adult

Topics: Adrenergic beta-Antagonists; Adult; Anesthesia, Intravenous; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Dexamethasone; Drug Therapy, Combination; Female; Graves Disease; Humans; Hypertension; Iopanoic Acid; Kidney Diseases; Methimazole; Preoperative Care; Propranolol; Tachycardia; Thyroidectomy

To compare survival times for cats with hyperthyroidism treated with iodine 131, methimazole, or both and identify factors associated with survival time.. Retrospective case series.. 167 cats.. Medical records of cats in which hyperthyroidism had been confirmed on the basis of high serum thyroxine concentration, results of thyroid scintigraphy, or both were reviewed.. 55 (33%) cats were treated with 131I alone, 65 (39%) were treated with methimazole followed by 131I, and 47 (28%) were treated with methimazole alone. Twenty-four of 166 (14%) cats had preexisting renal disease, and 115 (69%) had preexisting hepatic disease. Age was positively correlated (r = 0.4) with survival time, with older cats more likely to live longer. Cats with preexisting renal disease had significantly shorter survival times than did cats without preexisting renal disease. When cats with preexisting renal disease were excluded, median survival time for cats treated with methimazole alone (2.0 years; interquartile range [IQR], 1 to 3.9 years) was significantly shorter than median survival time for cats treated with 131I alone (4.0 years; IQR, 3.0 to 4.8 years) or methimazole followed by 131I (5.3 years; IQR, 2.2 to 6.5 years).. Results suggest that age, preexisting renal disease, and treatment type were associated with survival time in cats undergoing medical treatment of hyperthyroidism.

Topics: Age Factors; Animals; Antithyroid Agents; Cat Diseases; Cats; Drug Therapy, Combination; Female; Hyperthyroidism; Iodine Radioisotopes; Kidney Diseases; Male; Methimazole; Retrospective Studies; Survival Rate; Treatment Outcome

Hyperthyroidism and chronic renal disease occur commonly in geriatric cats, often in association with potentially life-threatening primary or secondary hypertension. Early treatment of hypertension minimizes damage to vital organs. This case illustrates the complexity of managing hypertension in a geriatric cat with both hyperthyroidism and renal disease.

Topics: Animals; Antihypertensive Agents; Antithyroid Agents; Cat Diseases; Cats; Diagnosis, Differential; Enalapril; Female; Hypertension; Hyperthyroidism; Kidney Diseases; Methimazole; Treatment Outcome

The aim of this study was to classify the protective mechanisms of DL-buthionine-(S,-R)-sulphoximine, glutathione and methimazole on cisplatin-induced nephrotoxicity in rats. An Emax model was used to study the effect of these compounds on the pharmacokinetics of cisplatin, especially renal handling and intra-renal biotransformation. Cisplatin (5 mg kg(-1)) was administered as an intravenous bolus to rats treated with either 0.9% NaCl (control), buthionine sulphoximine, glutathione or methimazole. The blood urea nitrogen level was monitored to estimate cisplatin-induced nephrotoxicity. To estimate renal handling of cisplatin, cisplatin was infused intravenously to rats treated with 0.9% NaCl, buthionine sulphoximine, glutathione or methimazole. The concentrations of unchanged cisplatin in plasma, urine and kidney were determined by a post-column derivatization HPLC method. The relationship between the pharmacokinetics and toxicodynamics of cisplatin was analysed using a sigmoid Emax model. All compounds studied ameliorated significantly the nephrotoxicity of cisplatin. The renal accumulation of cisplatin was reduced significantly by pretreatment with buthionine sulphoximine but not by either glutathione or methimazole. Although glutathione treatment did not affect the renal accumulation of cisplatin, it significantly decreased the binding of cisplatin to the intrarenal organelle and the decreased binding was well correlated to the decrease of the blood urea nitrogen level. In summary, pharmacokinetic-toxicodynamic analysis will be useful for classifying the protective mechanism of cisplatin-induced nephrotoxicity.

Topics: Animals; Antineoplastic Agents; Area Under Curve; Blood Urea Nitrogen; Buthionine Sulfoximine; Cisplatin; Glomerular Filtration Rate; Glutathione; In Vitro Techniques; Kidney; Kidney Cortex; Kidney Diseases; Male; Methimazole; Rats; Rats, Wistar; Temperature; Time Factors

Methimazole was previously shown to protect rats, mice, and (or) dogs against cisplatin-, cephaloridine-, 2-bromohydro-quinone-, and S-(1,2-dichlorovinyl)-L-cysteine-induced nephrotoxicity. In this study, methimazole effects on gentamicin (GM) induced nephrotoxicity were examined. Rats given GM (40 mg/kg) twice daily for 10 days exhibited higher blood urea nitrogen (BUN) concentrations and severe necrosis of virtually all proximal tubules compared with saline-treated controls. Rats cotreated with methimazole (20 mg/kg) exhibited minimal proximal tubular necrosis and were protected against GM-induced increase in BUN concentrations, despite having higher kidney GM concentrations. Rats given GM alone for 3 days exhibited no proximal tubular necrosis and no elevation of BUN values. However, these rats exhibited an increase in nonprotein disulfide concentrations and a decrease in renal protein thiol and protein disulfide concentrations, as opposed to rats given GM and methimazole. Together the results show that methimazole was an effective antagonist of GM-induced nephrotoxicity. Methimazole did not inhibit GM renal uptake but may protect against GM-induced nephrotoxicity by acting as an antioxidant within the kidneys.

Topics: Animals; Blood Urea Nitrogen; Gentamicins; In Vitro Techniques; Kidney Cortex; Kidney Diseases; Male; Methimazole; Rats; Sulfhydryl Compounds

The protective effect of methimazole, a commonly used antithyroid drug, on cisplatin-induced nephrotoxicity was studied. Eight dogs received 80 mg/m2 cisplatin i.v. without saline prehydration. Dogs were randomized into two groups of four dogs each: one group received 40 mg/kg methimazole i.p. at 30 min prior to and 4 h after cisplatin delivery, and the other group received saline placebo i.p. Methimazole protected dogs against the in vivo nephrotoxicity elicited by cisplatin as evidenced by clinicopathologic and histopathologic indices. Protection was not complete, as methimazole-treated animals developed mild histopathologic renal changes. Measures of renal oxidative stress did not differ between the two groups at day 5 following cisplatin treatment. No difference was noted for serum thyroxine concentrations before or after therapy in either group; however, serum levels of 3,5,3'-triiodothyronine were significantly higher on day 5 in both groups of dogs receiving cisplatin, regardless of whether they received methimazole or not. Methimazole as used in this study was found to be well tolerated in dogs over the short term, with no significant clinical or clinicopathologic toxicity being observed. The results of this study support the additional evaluation of methimazole as a protectant against cisplatin-induced nephrotoxicity using the dog as a model.

Topics: Animals; Cisplatin; Disease Models, Animal; Dogs; Glutathione; Kidney; Kidney Diseases; Male; Methimazole; Oxidation-Reduction; Pilot Projects; Random Allocation; Thyroxine; Triiodothyronine

Because methimazole has antioxidant properties, the effects of methimazole treatment on cephaloridine, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), 2-bromohydroquinone (2-BHQ) and cis-diaminedichloroplatinum (II) (cisplatin)-induced nephrotoxicity were investigated. Rats given cephaloridine (1 g/kg), cisplatin (5 mg/kg), DCVC (100 mg/kg) or 2-BHQ (157 mg/kg) i.p. exhibited significant elevations in blood urea nitrogen concentrations, which correlated with appearance of distinct renal histopathological changes. Cephaloridine, DCVC or 2-BHQ-induced nephrotoxicity was reduced only when methimazole (20-40 mg/kg) was given 30 min before the nephrotoxicant, whereas cisplatin-induced nephrotoxicity was reduced when methimazole was given 30 min before and up to 4 hr after cisplatin. Because the renal organic acid transport system plays an important role in the nephrotoxicity of cephaloridine, cisplatin and DCVC, the role of the organic acid transport system in the renal uptake of methimazole was investigated. With rat kidney cortical slices, methimazole uptake was time- and concentration-dependent; however, the organic acid transport substrates, probenecid (1 mM) and p-aminohippuric acid (7.5 mM), were ineffective in blocking methimazole uptake. Furthermore, cephaloridine (1 mM) uptake by kidney cortical slices was not affected by methimazole (5 mM). Rats given methimazole (40 mg/kg) 30 min before cephaloridine (2 g/kg) had serum and kidney cephaloridine concentrations similar to rats given cephaloridine only, but the methimazole-pretreated rats were significantly protected against cephaloridine-induced oxidation of renal nonprotein thiols. These results show that methimazole does not inhibit the transport of cephaloridine into the kidneys, but may protect against cephaloridine-induced renal damage by acting as an antioxidant within the kidneys.

Topics: Animals; Blood Urea Nitrogen; Cephaloridine; Cisplatin; Cysteine; Hydroquinones; Kidney; Kidney Diseases; Male; Methimazole; Oxidation-Reduction; Oxygen; Rats; Rats, Inbred Strains; Sulfhydryl Compounds

Topics: Adenoma; Animals; Antithyroid Agents; Carcinogens; Carcinoma, Hepatocellular; Cysts; Female; Glucose; Goiter; Imidazoles; Kidney Diseases; Lactates; Liver Neoplasms; Male; Methimazole; Methylthiouracil; Mice; Mice, Inbred Strains; Ovarian Cysts; Oxygen Consumption; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms; Triiodothyronine