Concomitant administration of atorvastatin with N-acetylcysteine mitigates liver injury and steatosis in experimental non-alcoholic fatty liver disease

Although numerous efforts have been directed toward searching for new treatments against non-alcoholic fatty liverdisease (NAFLD), there are no approved pharmacologic agents up to date. This study evaluates the therapeutic effectof concomitant administration of atorvastatin (ATO) and N-Acetylcysteine (NAC) with/without diet control. Ninegroups of rats were divided into: normal, rats fed on high-fat diet for 12 weeks (NAFLD-HFD model), HFD-ratsswitched to regular diet (NAFLD-RD model), NAFLD-HFD or -RD rats treated with either ATO or NAC orally with30 or 500 mg/kg/day, respectively, or both for 8 weeks. NAFLD-HFD rats exhibited remarkable steatosis with lobularinflammation, hepatocytes vacuolation, and fibrosis, as well as significant changes in lipid profile, oxidative stress,and adipocytokines and these manifestations were less prominent in the HFD-RD group. ATO and NAC combinationwith diet control has the added benefits on ameliorating lipid levels, liver enzymes, oxidative stress, hepatic steatosis(9.01% ± 1.66% vs. 13.21% ± 2.20% for ATO and 25.60% ± 2.11% for NAC), inflammation, hepatocyte vacuolation,and fibrosis versus each drug separately. Conclusion: ATO and NAC concomitant therapy has a greater effect onNAFLD as compared to monotherapy and is recommended for further investigation in clinical trials.

Rosmarinic acid attenuates hepatic fibrogenesis via suppression of hepatic stellate cell activation/proliferation and induction of apoptosis

OBJECTIVE@#To investigate the antifibrotic role of rosmarinic acid (RA), a natural polyphenolic compound, on HSCs activation/proliferation and apoptosis in vitro and in vivo.@*METHODS@#The impact of RA on stellate cell line (HSC-T6) proliferation, activation and apoptosis was assessed along with its safety on primary hepatocytes. In vivo, rats were divided into: (i) normal; (ii) thioacetamide (TAA)-intoxicated rats for 12 weeks; (iii) TAA + silymarin or (iv) TAA + RA. At the end of experiment, liver functions, oxidative stress, inflammatory and profibrogenic markers, tissue inhibitor metalloproteinases type-1 (TIMP-1) and hydroxyproline (HP) levels were evaluated. Additionally, liver histopathology and immunohistochemical examinations of alpha-smooth muscle actin (α-SMA), caspase-3 and proliferation cellular nuclear antigen (PCNA) were determined.@*RESULTS@#RA exhibited anti-proliferative effects on cultured HSCs in a time and concentration dependent manner showing an IC of 276 μg/mL and 171 μg/mL for 24 h and 48 h, respectively, with morphological reversion of activated stellate cell morphology to quiescent form. It significantly improved ALT, AST, oxidative stress markers and reduced TIMP-1, HP levels, inflammatory markers and fibrosis score (S1 vs S4). Furthermore, reduction in α-SMA plus elevation in caspase-3 expressions of HSCs in vitro and in vivo associated with an inhibition in proliferation of damaged hepatocytes were recorded.@*CONCLUSIONS@#RA impeded the progression of liver fibrosis through inhibition of HSCs activation/proliferation and induction of apoptosis with preservation of hepatic architecture.

Rosmarinic acid attenuates hepatic fibrogenesis via suppression of hepatic stellate cell activation/proliferation and induction of apoptosis

Objective To investigate the antifibrotic role of rosmarinic acid (RA), a natural polyphenolic compound, on HSCs activation/proliferation and apoptosis in vitro and in vivo. Methods The impact of RA on stellate cell line (HSC-T6) proliferation, activation and apoptosis was assessed along with its safety on primary hepatocytes. In vivo, rats were divided into: (i) normal; (ii) thioacetamide (TAA)-intoxicated rats for 12 weeks; (iii) TAA + silymarin or (iv) TAA + RA. At the end of experiment, liver functions, oxidative stress, inflammatory and profibrogenic markers, tissue inhibitor metalloproteinases type-1 (TIMP-1) and hydroxyproline (HP) levels were evaluated. Additionally, liver histopathology and immunohistochemical examinations of alpha-smooth muscle actin (α-SMA), caspase-3 and proliferation cellular nuclear antigen (PCNA) were determined. Results RA exhibited anti-proliferative effects on cultured HSCs in a time and concentration dependent manner showing an IC

Pharmacological and antioxidant actions of garlic and/or onion in non-alcoholic fatty liver disease [NAFLD] in rats

Non-alcoholic fatty liver disease [NAFLD] includes a broad spectrum of fat-induced liver injury, ranging from mild steatosis to cirrhosis and liver failure. This study investigates the hepatoprotective properties of garlic and onion in NAFLD rat model. Ninety male Sprague-Dawley rats were randomly divided into 9 groups; normal [I], NAFLD induced with high fat diet [HFD; II], NAFLD switched to regular diet [RD; III], NAFLD-HFD or NAFLD-RD treated with garlic [IV, V] onion [VI, VII] or the combined garlic+onion [VIII, IX] respectively. A NAFLD rat model was established by feeding the animals with a high-fat diet for 12 wk. These animals were then treated with garlic or/and onion or vehicle for 8 wk [weeks 13-20] and then killed to obtain serum samples and liver tissues. Liver histology, lipids, parameters of oxidative stress, TNF-alpha and TGF-p were measured. The liver in NAFLD-HFD showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration. Serum levels of ALT, AST, ALP, leptin, cholesterol, triglycerides, TNF-alpha, TGF-P and hepatic MDA were significantly increased [P<0.05] compared with normal group. This was accompanied with reduction of hepatic GSH, GR, GPx, GST, SOD and serum adiponectin. These changes were to a less degree in NAFLD-RD group. Combined administration of garlic+onion produced a better and significant decrease in liver steatosis, serum liver enzymes, oxidative markers and lipid peroxidation versus each one alone. In the same time, NAFLD-induced inflammation was also mitigated via reduction of TNF-alpha and TGF-P. In addition, these results were better in the group IX versus group VIII

[Professionalization experiences of newly employed nurses in clinical settings in Iran]

Nursing professionalization is a developmental experience that evolves throughout professional nurses' careers. Nursing systems that prepare nurses include experiences that are important in the early development of nursing identity. This phenomenenon is also foundational to the assumption of various nursing roles. A phenomenological approach was used in order to explore the meanings of professionalization experiences among participants. Data were gathered through series of semi structured interviews. Benner's interpretive method was used for data analysis. From 17 famale and male beginner nurses who worked in different educational and private hospitals in Tehran points of view 5 main themes and 4 subthemes emerged which encompasses the whole experiences of participants' professioalization experiences. These themes included sufficient knowledge, well practical experiences and autonomy in practice to provide a comprehensive care. Faculty understanding of beginning nurses' definitions and experiences of nursing professionalization can provide insights that can be used to develop educational experiences that support and enhance students' professional nursing identity and ultimately affect their future practice. Faculty can also use knowledge of nurses' definitions of professionalization to enrich student learning

Bone turnover markers in infertile women and patients with endometriosis under gonadotropin releasing hormone agonist [GnRH-a] and with add-back therapy

Gonadotropin releasing hormone agonist [GnRH-a] induces an acute reversible inhibition of ovarian function with an increase in bone turnover and significant bone loss. This study was conducted to evaluate the bone turnover in women under single and multiple injections of GnRH-a and also to determine the role of add-back therapy on bone turnover. Patients and The present study was designed to include 80 female patients under single injection [40 cases] and multiple injections [40 cases] of long acting GnRH-a with and without add back therapy [add back therapy was nasal salmon calcitonin 200 I.U daily supplement of 1gm calcium daily]. Biochemical bone turnover markers [serum calcium, phosphorus, alkaline phosphatase, osteocalcin and urinary deoxypyridinoline] were estimated. Determination of serum calcium and phosphorus showed no significant differences after two weeks, three months and six months of GnRH-a therapy. Serum alkaline phosphatase level was of no significant difference after two weeks and also after three and six months in the groups with add-back therapy. But after three and six months in the groups without using add-back therapy, it was significantly elevated. Serum osteocalcin and urinary deoxypyridinoline showed no significant changes after two weeks, three and six months of GnRH-a therapy with add-back therapy. But these markers were significantly increased after three and six months in group under GnRH-a therapy without use add-back therapy. A routine survey for females under GnRH-a therapy is recommended to identify subjects of. accelerated bone loss. Such survey should include serum osteocalcin and urinary deoxypyridinoline as these methods are reliable markers of bone turnover. Add-back therapy proved to be an effective measure against the induced bone loss during GnRH-a therapy