Erythropoietin Suppresses the Hepatic Fibrosis Caused by Thioacetamide: Role of the PI3K/Akt and TLR4 Signaling Pathways

Erythropoietin (EPO) is recognized for its function in erythropoiesis; however, its potential antifibrotic effect against liver fibrosis remains unknown. This study examined whether EPO affects thioacetamide (TAA)-induced liver fibrosis by concentrating on the Toll-like receptor 4 (TLR4) cascade and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway as possible pathways. Male Wistar rats were randomized into four groups, which included: the negative control group, the TAA group (intraperitoneal; TAA 100 mg/kg three times per week for 2 weeks), and EPO-treated groups (150 and 300 IU/kg, i.p.) for 2 weeks after TAA injections. EPO attenuated hepatic fibrosis in a dosage-dependent way, as manifested by the diminution in serum alanine aminotransferase and aspartate aminotransferase activities, as well as the increase in albumin level. EPO inhibited the increase in tissue levels of tumor necrosis factors-α, interleukin-1β, transforming growth factor-β1, and TLR4 and raised tissue levels of PI3K and p-PI3K. EPO antioxidant properties were demonstrated by restoring hepatic glutathione and superoxide dismutase by preventing the accumulation of hepatic malondialdehyde. Further, EPO increased the protein expression of PI3K and Akt and decreased TLR4 protein expression. Immunohistochemically, EPO treatment altered tissue histology and downregulated mitogen-activated protein kinase protein expression. Overall, the research suggested that EPO could prevent TAA-induced hepatic fibrosis through upregulating the PI3K/Akt signaling cascade and downregulation the TLR4 downstream axis

Effect of vitamin D3 in treating hyperthyroidism in patients with graves’ disease

Background Graves’ disease (GD) is an autoimmune disease characterized by hyperthyroidism secondary to circulating autoantibodies. Multiple factors contributed to its etiology, including genetic and environmental factors. The role of vitamin D is well-known in calcium metabolism and skeletal homeostasis. Vitamin D was shown to be a modulator in both innate and adaptive immunity. There is a link between vitamin D deficiency and various autoimmune diseases. The prevalence of vitamin D deficiency was reported to be common in patients with GD. Interestingly, vitamin D deficiency is found to be associated with higher thyroid volume in patients with newly-onset GD. However, vitamin D deficiency relationship with GD remains a controversial issue. Objective The objective of this study was to evaluate the effect of vitamin D supplementation in GD with and without ophthalmopathy. Patients and methods A randomized prospective study was conducted on 60 adult patients with GD aged 20–40 years. Group 1 comprised 20 patients with GD receiving a daily dose of 30 mg of methimazole alone. Group 2 comprised 40 patients with GD receiving the same dose of methimazole, supplemented with intramuscular injection of vitamin D3 200 000 IU/month for 3 months. Patients were followed up over a 3-month duration. Results There was hypovitaminosis D in all participants with a percentage of vitamin D deficiency (vitamin D level: <20 ng/ml) of 73.9% in male and 54.1% in female and a vitamin D insufficiency (vitamin D level: 20–29 ng/ml) of 26.1% in male and 45.9% in female. Vitamin D was significantly correlated with thyroid volume and degree of exophthalmos. On vitamin D supplementation, group 2 had significantly lower thyroid volume and better effect on the degree of exophthalmos. Conclusion Vitamin D supplementation for GD has a favorable effect on thyroid volume and on the degree of exophthalmos