scholarly journals Antifibrogenic Influence of Mentha piperita L. Essential Oil against CCl4-Induced Liver Fibrosis in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Hanan A. Ogaly ◽  
Nadia A. Eltablawy ◽  
Reham M. Abd-Elsalam
Keyword(s):  
Liver Fibrosis ◽  
Essential Oil ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Redox Status ◽  
Male Rats ◽  
Mentha Piperita ◽  
Control Group ◽  
Protective Effects ◽  
Cyp2e1 Gene

Essential oils of some aromatic plants provide an effective nonmedicinal option to control liver fibrosis. Mentha piperita L. essential oil (MPEO) have been reported to possess protective effects against hepatotoxicity. However, its effect against liver fibrosis remains unknown. The present study investigated the antifibrogenic potential of MPEO and its underlying mechanisms. Forty male rats divided into 4 groups were used: group 1 served as normal control, group 2 (liver fibrosis) received CCl4 (2.5 mL/kg, IP, twice weekly) for 8 weeks, group 3 concurrently received CCl4 plus MPEO (50 mg/kg, IP, daily, from the 3rd week), and group 4 received MPEO only. MPOE significantly improved the liver injury markers, lipid peroxidation (LPO), antioxidant capacity, CYP2E1 gene expressionand liver histology. Furthermore, MPOE ameliorated liver fibrosis as evidenced by the reduced expression of desmin, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and SMAD3 proteins. In addition, MPOE counteracted the p53 upregulation induced by CCl4 at both mRNA and protein levels. In conclusion, MPOE could effectively attenuate hepatic fibrosis mainly through improving the redox status, suppressing p53 and subsequently modulating TGF-β1 and SMAD3 protein expression. These data promote the use of MPOE as a promising approach in antifibrotic therapy.

Itraconazole Attenuates Peritoneal Fibrosis Through Its Effect on the Sonic Hedgehog Signaling Pathway in Mice

2018 ◽  
Vol 48 (6) ◽  
pp. 456-464 ◽  
Author(s):  
Jin Sug Kim ◽  
Kyung Sook Cho ◽  
Seon Hwa Park ◽  
Sang Ho Lee ◽  
Ji Hwan Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Isotonic Saline ◽  
Control Group ◽  
Protective Effects ◽  
Peritoneal Fibrosis ◽  
Shh Signaling ◽  
Itraconazole Treatment

Background: Peritoneal fibrosis is a devastating complication of peritoneal dialysis. However, its precise mechanism is unclear, and specific treatments have not yet been established. Recent evidence suggests that the sonic hedgehog (SHH) signaling pathway is involved in tissue fibrogenesis. Drugs that inhibit this pathway are emerging in the field of anti-fibrosis therapy. Itraconazole, an anti-fungal agent, was also recently recognized as an inhibitor of the SHH signaling pathway. In this study, we used a mouse model to investigate whether the SHH signaling pathway is involved in the development of peritoneal fibrosis and the effects of itraconazole on peritoneal fibrosis. Methods: Peritoneal fibrosis was induced by intraperitoneal (IP) injection of 0.1% chlorhexidine gluconate (CG) solution every other day for 4 weeks, with or without itraconazole treatment (20 mg/kg, IP injection on a daily basis). Male C57BL/6 mice were divided into 4 groups: saline group, saline plus itraconazole group, CG group, and CG plus itraconazole group. Isotonic saline was administered intraperitoneally to the control group. The peritoneal tissues were evaluated for histological changes, expression of fibrosis markers, and the main components of the SHH signaling pathway. Results: Peritoneal thickening was evident in the CG group and was significantly decreased by itraconazole administration (80.4 ± 7.7 vs. 28.2 ± 3.8 µm, p < 0.001). The expression of the following SHH signaling pathway components was upregulated in the CG group and suppressed by itraconazole treatment: SHH, patched, smoothened, and glioma-associated oncogene transcription factor 1. The IP injection of CG solution increased the expression of fibrosis markers such as α-smooth muscle actin and transforming growth factor-β1 in the peritoneal tissues. Itraconazole treatment significantly decreased the expression of these markers. Conclusion: Our study provides the first evidence that the SHH signaling pathway may be implicated in peritoneal fibrosis. It also demonstrates that itraconazole treatment has protective effects on peritoneal fibrosis through the regulation of the SHH signaling pathway. These findings suggest that blockage of the SHH signaling pathway is a potential therapeutic strategy for peritoneal fibrosis.

scholarly journals Renoprotective Effect of Platelet-Rich Plasma on Cisplatin-Induced Nephrotoxicity in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Neveen Salem ◽  
Nawal Helmi ◽  
Naglaa Assaf
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Male Rats ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Protective Effects ◽  
Intercellular Adhesion Molecule 1 ◽  
Histopathological Investigation

Platelet-rich plasma (PRP) has grown as an attractive biologic instrument in regenerative medicine for its powerful healing properties. It is considered as a source of growth factors that may induce tissue repairing and improve fibrosis. This product has proven its efficacy in multiple studies, but its effect on cisplatin-induced nephrotoxicity has not yet been elucidated. The present investigation was performed to estimate the protective impact of platelet-rich plasma against cisplatin- (CP-) evoked nephrotoxicity in male rats. Nephrotoxicity was induced in male Wistar rats by right uninephrectomy followed by CP administration. Uninephrectomized rats were assigned into four groups: (1) control group, (2) PRP group, (3) CP group, and (4) CP + PRP group. PRP was administered by subcapsular renal injection. Renal function, inflammatory cytokines, and growth factor level as well as histopathological investigation were carried out. Treatment with PRP attenuated the severity of CP-induced nephrotoxicity as evidenced by suppressed creatinine, blood urea nitrogen (BUN), and N-acetyl glucosaminidase (NAG) levels. Moreover, PRP depressed intercellular adhesion molecule-1 (ICAM-1), kidney injury molecule-1 (KIM-1), caspase-3, and transforming growth factor-beta 1 (TGF-β1) levels, while enhanced the epidermal growth factor (EGF) level. These biochemical results were reinforced by the histopathological investigation, which revealed restoration of normal renal tissue architectures. These findings highlight evidence for the possible protective effects of PRP in a rat model of CP-induced nephrotoxicity, suggesting a new avenue for using PRP to improve the therapeutic index of cisplatin.

scholarly journals Effects of Methanol Extract of Breadfruit (Artocarpus altilis) on Atherogenic Indices and Redox Status of Cellular System of Hypercholesterolemic Male Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Oluwatosin Adekunle Adaramoye ◽  
Olubukola Oyebimpe Akanni
Keyword(s):  
Methanol Extract ◽  
Dietary Cholesterol ◽  
Relative Weight ◽  
Redox Status ◽  
Cellular System ◽  
Male Rats ◽  
High Density Lipoproteins ◽  
Protective Effects ◽  
Artocarpus Altilis ◽  
Atherogenic Indices

We investigated the effects of methanol extract ofArtocarpus altilis(AA) on atherogenic indices and redox status of cellular system of rats fed with dietary cholesterol while Questran (QUE) served as standard. Biochemical indices such as total cholesterol (TC), triglycerides (TG), low- and high-density lipoproteins-cholesterol (LDL-C and HDL-C), aspartate and alanine aminotransferases (AST and ALT), lactate dehydrogenase (LDH), reduced glutathione, glutathione-s-transferase, glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and lipid peroxidation (LPO) were assessed. Hypercholesterolemic (HC) rats had significantly increased relative weight of liver and heart. Dietary cholesterol caused a significant increase (P<0.05) in the levels of serum, hepatic, and cardiac TC by 110%, 70%, and 85%, LDL-C by 79%, 82%, and 176%, and TG by 68%, 96%, and 62%, respectively. Treatment with AA significantly reduced the relative weight of the organs and lipid parameters. There were beneficial increases in serum and cardiac HDL-C levels in HC rats treated with AA. In HC rats, serum LDH, ALT, and AST activities and levels of LPO were increased, whereas hepatic and cardiac SOD, CAT, and GPx were reduced. All biochemical and histological alterations were ameliorated upon treatment with AA. Extract of AA had protective effects against dietary cholesterol-induced hypercholesterolemia.

scholarly journals Long-Term Aspartame Administration Leads to Fibrosis, Inflammasome Activation, and Gluconeogenesis Impairment in the Liver of Mice

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 82
Author(s):  
Isabela A. Finamor ◽  
Caroline A. Bressan ◽  
Isabel Torres-Cuevas ◽  
Sergio Rius-Pérez ◽  
Marcelo da Veiga ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Damage ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Elevated Serum ◽  
Inflammasome Activation ◽  
Related Factor ◽  
Type I ◽  
Artificial Sweetener

Background: Aspartame is an artificial sweetener used in foods and beverages worldwide. However, it is linked to oxidative stress, inflammation, and liver damage through mechanisms that are not fully elucidated yet. This work aimed to investigate the effects of long-term administration of aspartame on the oxidative and inflammatory mechanisms associated with liver fibrosis progression in mice. Methods: Mice were divided into two groups with six animals each: control and aspartame. Aspartame (80 mg/kg, via oral) or vehicle was administrated for 12 weeks. Results: Aspartame caused liver damage and elevated serum transaminase levels. Aspartame also generated liver fibrosis, as evidenced by histology analysis, and pro-fibrotic markers’ upregulation, including transforming growth factor β 1, collagen type I alpha 1, and alpha-smooth muscle actin. Furthermore, aspartame reduced nuclear factor erythroid 2-related factor 2 (Nrf2) activation and enzymatic antioxidant activity and increased lipid peroxidation, which triggered NOD-like receptor containing protein 3 (NLRP3) inflammasome activation and p53 induction. Furthermore, aspartame reduced peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) levels, possibly through p53 activation. This PGC-1α deficiency could be responsible for the changes in lipid profile in serum, total lipid accumulation, and gluconeogenesis impairment in liver, evidenced by the gluconeogenic enzymes’ downregulation, thus causing hypoglycemia. Conclusions: This work provides new insights to understand the mechanisms related to the adverse effects of aspartame on liver tissue.

Piceatannol increases the expression of hepatocyte growth factor and IL-10 thereby protecting hepatocytes in thioacetamide-induced liver fibrosis

2016 ◽  
Vol 94 (7) ◽  
pp. 779-787 ◽  
Author(s):  
Hazem Abd-Elgawad ◽  
Nashwa Abu-Elsaad ◽  
Amr El-Karef ◽  
Tarek Ibrahim
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Liver Function ◽  
Hepatocyte Growth Factor ◽  
Transforming Growth Factor ◽  
Histopathological Examination ◽  
Smooth Muscle Actin ◽  
Interleukin 10 ◽  
Hepatocyte Growth ◽  
Inflammatory Effect

Piceatannol is a polyphenolic analog of resveratrol that selectively inhibits the non-receptor tyrosine kinase-Syk. This study investigates the potential ability of piceatannol to attenuate liver fibrosis and protect hepatocytes from injury. Thioacetamide was injected in adult male mice (100 mg/kg, i.p., 3 times/week) for 8 weeks. Piceatannol (1 or 5 mg/kg per day) was administered by oral gavage during the last 4 weeks. Liver function biomarkers, tissue malondialdehyde (MDA), cytokeratin-18 (CK18), hepatocyte growth factor (HGF), and interleukin-10 (IL-10) were measured. Necroinflammation, fibrosis, expression of transforming growth factor (TGF)-β1, and α-smooth muscle actin (SMA) were scored by histopathological examination and immunohistochemistry. Obtained results showed ability of piceatannol (1 mg/kg) to restore liver function and reduce inflammation. It significantly (p < 0.001) reduced MDA, CK18, TGF-β1, and α-SMA expression, and increased HGF and IL-10. It can be concluded that piceatannol at low dose can inhibit TGF-β1 induced hepatocytes apoptosis and exerts an anti-inflammatory effect attenuating fibrosis progression.

Consequences of Microwave oven Exposed Diet on The Basal Lamina of Seminiferous Tubules of Mice

2021 ◽  
Vol 15 (8) ◽  
pp. 2141-2144
Author(s):  
Kishwar Naheed ◽  
Muhammad Saad Abdullah ◽  
Maria Yousaf ◽  
Humaira Ali ◽  
Fareeha Mushtaq ◽  
...  
Keyword(s):  
Basal Lamina ◽  
Treated Group ◽  
Testicular Tissue ◽  
Microwave Oven ◽  
Mentha Piperita ◽  
Seminiferous Tubules ◽  
Control Group ◽  
Protective Effects ◽  
Trial Methodology ◽  
Experimental Group

Usage of electronic gadgets like microwave oven is increasing day by day that heats the food by exposing it to electromagnetic radiations which has many hazardous effects on human health including fertility. Aim: To find the effects of microwave oven exposed diet on basal lamina of seminiferous tubules of mice alongwith protective effects of Mentha piperita and melatonin on the same tissue. Study Design: Randomized control trial. Methodology: Adult male mice (n=32) were divided into four groups. Control group (G1) received standard pellets prepared for mice. Second group (G2) was given mice pellets exposed to microwave oven. Third group (G3) received Mentha Piperita leaf extract along with mice pellets exposed to microwave oven and the fourth group (G4) received oral melatonin along with pellets exposed to microwave oven. Later their testicular tissue was removed for histological examination while basal lamina disruption was assessed by scoring. Data analyzed by SPSS 22.0v. Results: In group G2, there was slight disruption in the basal lamina in 75% of the cases while in experimental group G3, there was slight disruption of basal lamina only in 12.5% of the cases. However, in group G4, only 25% specimen had slight disruption of basal lamina Conclusion: It was concluded that microwave oven exposed diet produced severe disruption of basal lamina in group G2 that decreased in Mentha piperita and melatonin treated groups. However, Mentha piperita treated group produced better results than melatonin treated group. Keywords: Mice, Testis, Basal Lamina, Mentha piperita and Melatonin

scholarly journals Sestrin 2 Attenuates Rat Hepatic Stellate Cell (HSC) Activation and Liver Fibrosis via an mTOR/AMPK-Dependent Mechanism

2018 ◽  
Vol 51 (5) ◽  
pp. 2111-2122 ◽  
Author(s):  
Yi-Bing Hu ◽  
Xiao-Ting Ye ◽  
Qing-Qing Zhou ◽  
Rong-Quan Fu
Keyword(s):  
Liver Fibrosis ◽  
Protein Expression ◽  
Hepatic Fibrosis ◽  
Transforming Growth Factor ◽  
Histopathological Examination ◽  
Stellate Cell ◽  
Smooth Muscle Actin ◽  
Mrna Levels ◽  
Alpha Smooth Muscle Actin

Background/Aims: Sestrin 2 is associated with the pathophysiology of several diseases. The aim of this study was to investigate the effects and potential mechanisms of Sestrin 2 in rat hepatic stellate cells (HSCs) during liver fibrogenesis. Methods: In this study, Sestrin 2 protein expression was detected in rat HSC-T6 cells challenged with transforming growth factor-β (TGF-β) and in mice treated with carbon tetrachloride (CCl4), a well-known model of hepatic fibrosis. Next, HSC-T6 cells and fibrotic mice were transfected with lentivirus. The mRNA expression levels of markers of liver fibrosis [alpha-smooth muscle actin (α-SMA) and collagen 1A1 (Col1A1)] were analyzed by quantitative reverse transcription–polymerase chain reaction (RT-PCR). Cell death and proliferation were evaluated by the MTT assay, and biochemical markers of liver damage in serum [alanine transaminase (ALT) and aspartate transaminase (AST)] were also measured using a biochemical analyzer. Histopathological examination was used to evaluate the degree of liver fibrosis, and protein expression [phospho-adenosine monophosphate-activated protein kinase (p-AMPK), AMPK, phospho-mammalian target of rapamycin (p-mTOR), and mTOR] was determined by western blotting. Results: We found that Sestrin 2 was elevated in both the HSC-T6 cell and hepatic fibrosis models. In vitro, overexpression of Sestrin 2 attenuated the mRNA levels of α-SMA and Col1A1, suppressed α-SMA protein expression, and modulated HSC-T6 cell proliferation. In vivo, overexpression of Sestrin 2 reduced the ALT and AST levels as well as the α-SMA and Col1A1 protein expression in the CCl4 model of liver fibrosis. Moreover, the degree of liver fibrosis was ameliorated. Interestingly, overexpression of Sestrin 2 increased p-AMPK but decreased p-mTOR protein expression. Conclusion: Our findings indicate that Sestrin 2 may attenuate the activation of HSCs and ameliorate liver fibrosis, most likely via upregulation of AMPK phosphorylation and suppression of the mTOR signaling pathway.

scholarly journals Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Song Sun ◽  
Menghua Xu ◽  
Peijun Zhuang ◽  
Gong Chen ◽  
Kuiran Dong ◽  
...  
Keyword(s):  
Vitamin D ◽  
Liver Fibrosis ◽  
Biliary Atresia ◽  
Transforming Growth Factor ◽  
Serum Vitamin ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Control Group ◽  
Serum Vitamin D ◽  
Duct Ligation ◽  
Tgf Β1

AbstractTo investigate the mechanism of 25 hydroxyvitamin D (25(OH)D) deficiency in children with biliary atresia (BA) and its effect on liver fibrosis. The serum vitamin D and 25(OH)D, and expression of 25 hydroxylase (CYP2R1 and CYP27A1) in the liver of BA patients were detected and compared with those in the control group. We investigated the effect of differential expression of CYP2R1 in hepatocytes on the expression of genes related to liver fibrosis in primary hepatic stellate cells (HSCs) of BA and animal models of cholestasis. The ratio of 25(OH)D/vitamin D in the BA group was significantly lower than that in the control group. The mRNA and protein expression of CYP2R1 and CYP27A1 in liver tissue of the BA group was significantly lower than that in the control group. Exogenous active vitamin D (calcitriol) inhibited the proliferation and migration of primary HSCs isolated from BA patients, and reduced the expression of fibrosis-related genes in vitro. Downregulation of expression of CYP2R1 in hepatocytes increased expression of transforming growth factor (TGF)-β1, collagen (Col)-1α1 and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased the expression of matrix metalloproteinase (MMP)-2 in cocultured primary HSCs of BA. Upregulation of expression of CYP2R1 in mice with bile duct ligation significantly increased the level of 25(OH)D, decreased the expression of TGF-β1, Col-1α1 and TIMP-1, and increased the expression of MMP-2. Children with BA have impaired vitamin D activation due to CYP2R1 deficiency. The dysactivation of vitamin D can promote the proliferation and activation of HSCs and participate in the development of hepatic fibrosis in BA.

scholarly journals Hierarchical Coculture of Hepatocyte and Hepatic Non-Parenchymal Cells for Liver Fibrosis Studies in vitro

2020 ◽  
Author(s):  
Qiao You Lau ◽  
Fuad Gandhi Torizal ◽  
Marie Shinohara ◽  
Yasuyuki Sakai
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Oxygen Tension ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Liver Sinusoidal Endothelial Cell ◽  
Type I ◽  
Parenchymal Cells

During chronic liver injury, inflammation leads to the development of liver fibrosis&mdash; particularly due to the activation of hepatic stellate cells (HSCs). However, the involvement of inflammatory cytokines in HSC activation is unclear. Many existing in vitro liver models do not include these non-parenchymal cells (NPCs), and hence, do not represent the physiological relevance found in vivo. Herein, we demonstrated the hierarchical coculture of primary rat hepatocytes with NPCs such as the human-derived HSC line (LX-2) and the human-derived liver sinusoidal endothelial cell line (TMNK-1). The coculture tissue had higher albumin production and hepatic cytochrome P450 3A4 activity compared to the monoculture. We then further studied the effects of stimulation by both oxygen tension and key pro-fibrogenic cytokines, such as the transforming growth factor beta (TGF-&beta;), on HSC activation. Gene expression analysis revealed that lower oxygen tension and TGF-&beta;1 stimulation enhanced collagen type I, III, and IV, alpha-smooth muscle actin, platelet-derived growth factor, and matrix metallopeptidase expression from LX-2 cells in the hierarchical coculture after fibrogenesis induction. This hierarchical in vitro cocultured liver tissue could, therefore, provide an improved platform as a disease model for elucidating the interactions of various liver cell types and biochemical signals in liver fibrosis studies.

Protective effect of vanillin against carbon tetrachloride (CCl4)-induced oxidative brain injury in rats

2011 ◽  
Vol 28 (7) ◽  
pp. 655-662 ◽  
Author(s):  
Mohamed Makni ◽  
Yassine Chtourou ◽  
Mohamed Barkallah ◽  
Hamadi Fetoui
Keyword(s):  
Carbon Tetrachloride ◽  
Protective Effect ◽  
Brain Damage ◽  
Glutathione Transferase ◽  
Single Injection ◽  
Male Rats ◽  
Control Group ◽  
Protective Effects ◽  
Degree Of Protection ◽  
Oxidative Brain Injury

This study investigated the protective effects of vanillin against acute brain damage induced by carbon tetrachloride (CCl4) in rats. The study was performed on 32 male rats divided into four groups: a control group, vanillin group ([Va] 150 mg/kg/day, intraperitoneally [i.p.]) and CCl4 toxication groups received a single injection of CCl4 (1 ml/kg, i.p.; CCl4 and Va + CCl4 groups). The degree of protection in brain tissue was evaluated by the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase, glutathione transferase, glutathione peroxidase and nitric oxide (NO). Vanillin showed a significant brain-protective effect by decreasing the level of lipid peroxidation and NO2 and elevated the activities of antioxidative enzymes and level of GSH. Consequently vanillin blocked oxidative brain damage induced by CCl4 in rats.

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