دانلود مقاله کاهش کم کاری تیروئید مرتبط با اختلال کبدی با ویتامین D
خلاصه
1. معرفی
2. مواد و روش ها
3. نتایج
4. بحث
5. نتیجه گیری ها
بیانیه مشارکت نویسنده
بیانیه تامین مالی
بیانیه در دسترس بودن داده ها
اطلاعات تکمیلی
اعلامیه منافع رقابتی
قدردانی ها
منابع
Abstract
1. Introduction
2. Material and methods
3. Results
4. Discussion
5. Conclusions
Author contribution statement
Funding statement
Data availability statement
Additional information
Declaration of competing interest
Acknowledgments
References
چکیده
ارتباط پیچیده ای بین هورمون های تیروئید (THs) و عملکرد کبد وجود دارد. کم کاری تیروئید به عنوان ناتوانی غده تیروئید در تولید هورمون های تیروئید کافی برای برآوردن نیازهای متابولیک بدن، ممکن است ساختار و عملکرد کبد را مختل کند. شواهد جدید حاکی از اثرات محافظتی ویتامین D در برابر آسیب کبدی است. در اینجا، این مطالعه با هدف بررسی نقش ویتامین D در آسیب کبدی مرتبط با کم کاری تیروئید انجام شد. 40 موش صحرایی نر از نژاد ویستار به 4 گروه: کنترل، گروه کم کاری تیروئید (Hypo) PTU 05/0 درصد، گروه های هیپو ویتامین D 100 و 500 واحد بین المللی بر کیلوگرم ویتامین D خوراکی از طریق گاواژ به مدت 6 هفته تقسیم شدند. سطح سرمی عملکرد کبد شامل آلانین آمینوترانسفراز (ALT)، آسپارتات آمینوترانسفراز (AST) و آلکالین فسفاتاز (ALP) اندازه گیری شد. سطح مالون دی آلدئید (MDA)، فعالیت آنزیم سوپراکسید دیسموتاز (SOD) و محتوای تیول کل به عنوان شاخص‌های استرس اکسیداتیو در بافت کبد اندازه‌گیری شد. علاوه بر این، برای تخمین فیبروز بافت کبد، رنگ آمیزی تری کروم ماسون انجام شد.
یافته های ما نشان داد که فیبروز کبدی ناشی از کم کاری تیروئید با افزایش سطوح ALT، AST و ALP مرتبط است. اگرچه، تجویز ویتامین D می تواند به طور قابل توجهی ALT، AST و ALP را در سرم کاهش دهد و تجمع فیبرهای کلاژن را سرکوب کند. علاوه بر این، فعالیت SOD و محتوای تیول کل به طور قابل توجهی کاهش یافت، در حالی که محتوای MDA به طور قابل توجهی در موش های هیپوتیروئید ناشی از PTU نسبت به گروه کنترل افزایش یافت. با این وجود، درمان با ویتامین D نشانگرهای استرس اکسیداتیو ذکر شده را در گروه های هیپوویتامین D بهبود بخشید. در نتیجه، ویتامین D به دلیل خواص آنتی اکسیدانی و ضد فیبروتیک بالقوه خود می تواند در کاهش آسیب کبدی مرتبط با کم کاری تیروئید موثر باشد.
Abstract
There is a complex correlation between thyroid hormones (THs) and liver function. Hypothyroidism as a failure of the thyroid gland to produce adequate thyroid hormones to fulfill the metabolic requirements of the body, may perturb liver structure and function. Emerging evidence suggests the protective effects of vitamin D against liver damage. Herein, this study aimed to investigate the role of vitamin D in hypothyroidism-associated liver injury. Forty male Wistar rats were classified into 4 groups: control, hypothyroid (Hypo) group received 0.05% PTU, Hypo- Vitamin D groups were given 100 and 500 IU/kg vitamin D orally via gavage for 6 weeks. Serum level of liver function including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured. Malondialdehyde (MDA) level, superoxide dismutase (SOD) enzyme activity, and total thiol content were measured as oxidative stress indicators in the liver tissue. Furthermore, to estimate liver tissue fibrosis, Masson's trichrome staining was done.
Our findings showed that hypothyroidism-induced liver fibrosis was associated with increased levels of ALT, AST and ALP. Though, vitamin D administration could significantly reduce the ALT, AST and ALP in the serum and suppress the accumulation of collagen fibers. Moreover, the activity of SOD and total thiol content was notably reduced, while the MDA content was significantly increased in the PTU- induced hypothyroid rats compared to the control group. Nonetheless, treatment with vitamin D improved mentioned oxidative stress markers in the Hypo-vitamin D groups. In conclusion, vitamin D due to its potential antioxidant and anti-fibrotic properties could be effective in the decrease of hypothyroidism-associated liver injury.
Introduction
Thyroid hormones (THs) play an essential role in tissue growth and normal functioning throughout the life [1,2]. Also, THs have important roles in the regulation of energy metabolism, mitochondrial activity, and active oxygen metabolism [2]. The liver is the major site of the peripheral metabolism of THs. Liver and the thyroid has been well documented to be closely linked, with THs playing essential roles in beta-oxidation as well as cholesterol and carbohydrate metabolism [3]. Therefore, hypothyroidism is associated with unusual lipid patterns with an increase in low-density lipoprotein (LDL) levels as well as higher total cholesterol levels [4]. On the other hand, hypothyroidism is implicated in the etiology of fibrosis and is accompanied with increased production of mucopolysaccharides, resulting in interstitial fibrosis and extracellular water retention [5,6]. The progress of fibrosis is attributable to an abnormal response determined by the accumulation of extracellular matrix proteins such as collagen and fibronectin [7]. In addition, it has been suggested that hypothyroidism can be associated with oxidative stress [8]. Indeed, hypothyroidism by changing lipid panels and increasing reactive oxygen species (ROS) generation enhances tissue oxidative damage [9]. Animal studies have shown that hypothyroidism is in correlation with an increase in the levels of biochemical markers of oxidative stress and reducing the antioxidant levels in liver tissue [2,10]. Moreover, researchers have indicated that there is a positive connection between tissue oxidative damage and fibrosis [11,12]. In the fibrotic liver, damage to hepatic cells disrupts mitochondrial chain function and increases the production of free radicals as a result of lipid peroxidation, as well as activate Kupffer cells, and hepatic stellate cells (HSCs). Among liver cells, HSCs and Kupffer cells play critical roles in fibrosis. In the fibrotic liver, Kupffer cells via releasing profibrogenic factors such as transforming growth factor beta (TGF-β) trigger HSCs activation. HSCs are the predominant precursor cells of liver myofibroblasts and upon activation, by TGF-β, fibrogenic myofibroblasts up-regulate production and deposition of α-smooth muscle actin and extracellular matrix proteins, the most abundant one being type I collagen. Likewise, experimental studies have shown that hypothyroidism can induce up-regulation of collagen type 1 gene expression, causing subsequent fibrosis [[13], [14], [15], [16]].
Conclusions
Our results suggest that thyroid dysfunction is associated with liver damage characterized by abnormal liver function tests as well as liver fibrosis and redox homeostasis. On the other hand, vitamin D supplementation could ameliorate oxidative injury along with changes in liver structure and function in the hypothyroid animals. Vitamin D, with its unique protective effects, has the potential to be repurposed as a therapeutic agent for hepatic diseases associated with fibrosis. Nevertheless, more research still needs to be focused on the regulatory role of vitamin D in inhibiting liver fibro-genesis and to assess the safety and efficiency of this supplementation as a widely available and relatively inexpensive treatment for liver fibrotic conditions.