ABSTRACT
BACKGROUND: As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The present study aimed to evaluate the protective effects of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analog), individually or in combination, on streptozotocin (STZ)-diabetes-induced testicular dysfunction in rats and to identify the possible mechanisms for this protection. MATERIAL AND METHODS: This study was carried out on 50 male Sprague-Dawley rats; 10 normal rats were allocated as a non-diabetic control group. A total of 40 rats developed diabetes after receiving a single dose of STZ; then, the diabetic rats were divided into four groups of equivalent numbers assigned as diabetic control, enalapril-treated, paricalcitol-treated, and combined enalapril-and-paricalcitol-treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress, and inflammatory parameters, as well as histopathological examinations, were assessed in comparison with the normal and diabetic control rats. RESULTS: As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle-stimulating hormone (FSH) as well as luteinizing hormone (LH), and the antioxidant enzyme activities, were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly increased, along with severe distortion of the testicular structure. Interestingly, treatment with paricalcitol and enalapril, either alone or in combination, significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH, and LH, reduced insulin resistance, IL-6, and TNF-α levels, and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage, with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs compared to monotherapy with enalapril alone. CONCLUSIONS: Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties) compared with monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.
ABSTRACT
BACKGROUND: Many hypothyroid patients are not tolerant and not satisfied with levothyroxine (LT4). Older studies used large doses of both carbimazole and LT4 for Hashimoto's thyroiditis (HT), because Graves' disease (GD) and HT were considered as very closely related syndromes produced by thyroid autoimmunity. OBJECTIVE: The aim of the study was to determine the outcome after adding small doses of carbimazole to reduced doses of LT4 for patients with primary hypothyroidism, who are unable to tolerate LT4. METHODS: The study is a non-randomized, single arm, interventional study. It included 19 female patients diagnosed with primary hypothyroidism who could not tolerate LT4. Subjects were recruited from the outpatient clinic of AL-Azhar University Hospital in Damietta, Egypt from January to March 2015. They were divided into two groups; group 1 included 10 patients with HT and 2 patients with non-specified primary hypothyroidism, and group 2 included 7 patients with subtotal thyroidectomy for GD. All patients received carbimazole (10 mg/day) beside LT4 (25 µg thrice/week) for 10 weeks. Statistical analysis of the data was done by SPSS version 20, using paired-sample t-test, ANOVA, Chi square, and Pearson coefficient test. RESULTS: There was significant increase in free triiodothyronine (FT3) in addition to significant improvement in depression and LT4 tolerance in the whole population. There was non-significant improvement in TSH in group 1 (p=0.053). Surprisingly, in group 2, in spite of significant increase in TSH (p=0.007) and non-significant decrease in free thyroxine (FT4), there was non-significant increase in FT3. Whether carbimazole improves the pathology of the hypothyroid gland or the peripheral deiodination of T4 to T3 (where the serum and tissue levels of the latter may be responsible for improvement of symptoms) is in need of investigation. CONCLUSIONS: Adding carbimazole to LT4 improves FT3, LT4 tolerance, and depression in primary hypothyroid female patients. Further studies are required to determine the appropriate doses of this regimen in different cases. CLINICAL TRIAL REGISTRATION: This study was registered at Thai Clinical Trials Registration center (http://www.clinicaltrials.in.th) with registration ID: TCTR20170123003. FUNDING: The study received no fund or grant.
