scholarly journals Antioxidant and Anti-Inflammatory Effects of Origanum majorana L. Methanolic Extract on Bile Duct Ligation in Male Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Izadpanah Gheitasi ◽  
Nikta Motaghi ◽  
Hossein Sadeghi ◽  
Heibatollah Sadeghi ◽  
Zahra Moslemi ◽  
...  

Introduction. Cholestasis is caused by malfunction of the hepatobiliary system. This disorder is the result of the accumulation of bile fatty acids and other toxins in the liver. The aim of the current study was to investigate the antioxidative and hepatoprotective effects of methanolic extract of Origanum majorana L. (OM) on hepatic disorder and tissue damage induced by bile duct ligation (BDL) in rats. Materials and methods. Twenty-eight male Wistar rats were randomly divided into 4 groups including sham control group received vehicle (SC-V), bile duct ligation received vehicle (BDL-V), bile duct ligation group received OM extract (BDL + OM), and sham control group received OM extract (SC + OM). One day after surgery, the animals received vehicle or methanolic extract of OM 300 mg/kg/day for 7 consecutive days by oral gavage. Finally, the animals were anesthetized and the blood samples were collected from each animal. After sacrificing of animals, liver tissue from each rat was removed and divided into three parts: one part was used for preparing of homogenized tissue, one part was fixed in 10% neutral formalin for histopathology examination, and the third part was kept in liquid nitrogen for gene expression analysis. Biomarkers of oxidative stress in the liver tissue and serum, as well as histopathological changes of the liver, were assessed. Also, the gene expression of IL-1, TNF-α, TGF-β, and α-SMA has been measured. Results. The results showed that BDL-V significantly increased the activity of ALT, AST, ALP, and total bilirubin compared to the SC-V group. The oxidative stress markers such as MDA and FRAP significantly increased due to BDL, while the CAT activity reduced in the BDL-V group compared to SC-V group. Oral treatment with OM reduced ALT and AST activity, although it was not statistically significant. OM treatment considerably increased the activity of CAT compared to BDL group. BDL-V induced a significant histological change in the liver, while treatment with OM at a dose of 300 mg/kg showed a minor effect on histopathological changes. In addition, the mRNA of IL-1, TNF-α, TGF-β, and α-SMA significantly increased in the BDL-V group, while treatment with OM only significantly reduced TGF-β in comparison with BDL-V rats. Conclusions. The results of the present study showed that oral administration of OM extract had a moderate protective effect on cholestasis due to BDL. Indeed, more studies with different doses of extract are needed to confirm this finding.

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Zahra Moslemi ◽  
Hassan Bardania ◽  
Izadpanah Gheitasi ◽  
Zahra Barmoudeh ◽  
Navid Omidifar ◽  
...  

Herbal medicines harbor essential therapeutic agents for the treatment of cholestasis. In this study, we have assessed the anticholestatic potential of Stachys pilifera Benth’s (SPB’s) hydroalcoholic extract encapsulated into liposomes using bile duct ligation- (BDL-) induced hepatic cholestasis in rats. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), malondialdehyde (MDA), total thiol (T-SH) content, protein carbonyl (PCO), total bilirubin (TBIL), albumin (ALB), and nitric oxide (NO) metabolite levels were measured in either liver tissue or plasma to assess liver damage. Moreover, expression of proinflammatory cytokines (IL-1β and TNF-α) and liver fibrosis markers (TGF-β and SM-α) which are driving forces of many liver disorders was also determined. The activity of AST, ALT, and ALP was significantly enhanced in the BDL group in comparison to the control group; however, treatment with liposomal (SPB) hydroalcoholic extract significantly reduced AST and ALT’s activity. Increases in MDA, TBIL, and NO levels and T-SH content due to BDL were restored to control levels by liposomal (SPB) hydroalcoholic extract treatment. Similarly, hepatic and plasma oxidative marker MDA levels, significantly enhanced by BDL, were significantly decreased by liposomal (SPB) hydroalcoholic extract treatment. Moreover, histopathological findings further demonstrated a significant decrease in hepatic damage in the liposomal (SPB) hydroalcoholic extract-treated BDL group. In addition, liposomal (SPB) hydroalcoholic extract treatment decreased the liver expression of inflammatory cytokines (IL-1β, TNF-α) and liver fibrosis markers (TGF-β and SM-α). Since liposomal (SPB) hydroalcoholic extract treatment alleviated the BDL-induced injury of the liver and improved the hepatic structure and function more efficiently in comparison to free SPB hydroalcoholic extract, probable liposomal (SPB) hydroalcoholic extract exhibits required potential therapeutic value in protecting the liver against BDL-caused oxidative injury.


2021 ◽  
pp. 096452842110392
Author(s):  
Yu-Sheng Chen ◽  
Chorng-Kai Wen ◽  
Geng-Hao Liu ◽  
Tzung-Yan Lee

Background: A hyperdynamic circulation and impaired vascular responsiveness to vasoconstrictors are observed in portal hypertension (PHT) rats. Inflammation is a major contributor to the hyperdynamic circulation state in murine models of PHT. Electroacupuncture (EA) may ameliorate the inflammatory response and limit arterial vasodilatation and portal pressure. This study investigated the possible mechanisms underlying putative hemodynamics effects of EA in normal and PHT rats. Methods: PHT was induced by bile duct ligation (BDL) surgery over 4 weeks in rats. Sham-operated and BDL rats were treated with low-frequency EA (2 Hz) at ST36 10 min three times weekly for one or two consecutive weeks (for a total of 3 or 7 treatments, respectively). Serum tumor necrosis factor-α (TNF-α), nitrite/nitrate (NOx) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were analyzed, and hemodynamic variation and contractile responses to phorbol-12,13-dibutyrate and phenylephrine in aortic and superior mesenteric arterial rings were recorded. Inducible (i) and endothelial (3) nitric oxide synthase (NOS), cyclooxygenase-1 (COX-1), and protein kinase C-α (PKC-α) levels were determined by Western blotting. Results: EA significantly reduced portal pressure and serum TNF-α, NOx and 6-keto-PGF1α levels compared to the untreated BDL group, enhanced maximum contractile responses in the aorta, up-regulated PKC-α, and down-regulated iNOS and COX-1 levels. In addition, EA decreased the aortic angiogenesis signaling cascade, reflected by down-regulation of vascular endothelial growth factor (VEGF) abundance and transforming growth factor β receptor (TGFβR)I/II expression, as assessed by immunostaining. Conclusion: EA attenuates TNF-α, NO and 6-keto-PGF1α overproduction, modulates the vascular levels of constitutive NOS and PKC-α, blunts the development of the angiogenesis cascade, and enhances vascular contractile force in PHT rats.


2003 ◽  
Vol 285 (1) ◽  
pp. C183-C194 ◽  
Author(s):  
Gianfranco Alpini ◽  
Yoshiyuki Ueno ◽  
Laura Tadlock ◽  
Shannon S. Glaser ◽  
Gene LeSage ◽  
...  

Tumor necrosis factor (TNF)-α plays a critical role in epithelial cell injury. However, the role of TNF-α in mediating cholangiocyte injury under physiological or pathophysiological conditions is unknown. Thus we assessed the effects of TNF-α alone or following sensitization by actinomycin D on cell apoptosis, proliferation, and basal and secretin-stimulated ductal secretion in cholangiocytes from normal or bile duct-ligated (BDL) rats. Cholangiocytes from normal or BDL rats were highly resistant to TNF-α alone. However, presensitization by actinomycin D increased apoptosis in cholangiocytes following BDL and was associated with an inhibition of proliferation and secretin-stimulated ductal secretion. Thus TNF-α mediates cholangiocyte injury and altered ductal secretion following bile duct ligation. These observations suggest that cholestasis may enhance susceptibility to cytokine-mediated cholangiocyte injury.


2021 ◽  
Author(s):  
Bronislava Gedulin ◽  
Marina Safonov ◽  
Vladimir L. Safonov

ABSTRACTBackgroundHydrogen was determined to have good efficacy for reducing key blood level biomarkers associated with liver injury suggesting the compound may provide novel option for the treatment of several liver diseases by decreasing of accumulation of toxins and reduction of levels of serum liver enzymes.Materials and methodsThe present pharmacological study was conducted to evaluate the effectiveness of a gastric hydrogen generating powder called “AquaActive” (AA) in a rat model of liver injury, the partial bile duct ligation (pBDL), following administration of 0.2% AA formulated in rat pellets food for 14 days.ResultsThe data indicate that treatment with AA at a dose of 150 mg/kg/day can effectively slow the progression of liver injury that is triggered by bile duct ligation in rats. At both 7 and 14 days post-pBDL surgery, treatment with AA exhibited reductions in ALT, AST, ALP, GGT and total bilirubin, most of which were statistically significant. At 7 days, the compound showed statistically significant decreases in ALP, GGT and total bilirubin levels. Although the values of some parameters decreased in the vehicle group by 14 days, additional reductions due to AA treatment were sustained for ALP, AST and for GGT and total bilirubin. GGT and total bilirubin level after 14 days of treatment compared to the vehicle-treated control group were observed to be highly significant (p<0.05).ConclusionThus AA, gastric hydrogen generating powder demonstrated a good efficacy for reducing key parameters associated with liver function in the pBDL model.


2004 ◽  
Vol 22 (6) ◽  
pp. 359-363 ◽  
Author(s):  
İbrahim Halil Bahçecıoğlu ◽  
Mehmet Yalniz ◽  
Hüseyin Ataseven ◽  
Nurullah Bülbüller ◽  
Muzaffer Keçecı ◽  
...  

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
E A Abushady ◽  
S M Elagaty ◽  
N A Nassef ◽  
G S Abdelhamid

Abstract Background cholestasis is a prevalent health problem associated with liver oxidative stress, inflammation, and fibrosis. Quercetin has been shown to afford a beneficial effect in a variety of liver diseases. Aim This study was designed to investigate the potential protective effect of quercetin on liver cholestasis and the possible underlying mechanisms in a rat model of bile duct ligation (BDL). Design Experimental study Methods This study was carried out on adult male Wister rats which were randomly divided into: Sham, BDL and BDL- quercetin treated (BDL- Q) groups. Quercetin was given by gavage in a dose of 50 mg/kg/day. Results Bile duct ligation resulted in a significant increase in serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and liver levels of myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-α),and transforming growth factor beta 1(TGF-β1), along with a significant decrease in serum levels of total proteins (TP) and liver glutathione peroxidase(GPX) in BDL group versus sham group. Quercetin treatment significantly lowered serum levels of AST, ALT, ALP, and MPO, TNF-α, and TGF-β1 in liver tissues associated with a significant increase in serum TP and liver GPX in BDL-Q group versus BDL rats. Histological studies revealed enhancement of inflammation and a significant increase in the percentage area of collagen deposition in BDL versus sham group. These changes were attenuated in BDL-Q group compared to BDL rats. Conclusions Quercetin alleviated cholestasis induced liver injury and improved liver function possibly via attenuating liver oxidative stress, inflammation and fibrosis.


Author(s):  
Weimin kong ◽  
Xueying Sun ◽  
Siyu Yu ◽  
Peihua Liu ◽  
Xiaoke zheng ◽  
...  

Background and Purpose Liver failure is often associated with psychiatric alterations, partly resulting from the increased dopamine levels in brain. We aimed to investigate relationship between increased dopamine levels and mental abnormalities using bile duct ligation (BDL) rats and document mechanism that liver failure increased dopamine levels in SH-SY5Y cells. Experimental Approach Psychiatric alterations were operated following 14-day BDL. Dopamine and its metabolite levels in cortex, expressions of enzymes and transporters related to dopamine metabolism and transport in cortex and hippocampus were measured. SH-SY5Y cells were used to investigate whether NH4Cl, bile acids and bilirubin affected expression of tyrosine hydroxylase (TH) or not. TH expression in SH-SY5Y cells co-incubated with bilirubin and signal pathway inhibitors was measured. Key Results Open-field test results showed a remarkable increase in exploratory behavior following BDL. BDL increased dopamine levels and expression of TH protein in cortex. MAO-A and Mb-COMT slightly but significantly decreased. Data from SH-SY5Y cells showed that increased bilirubin levels was a factor in inducing TH expression. Both inhibitor of NF-κB pathway BAY117082 and silencing p65 remarkably reversed bilirubin-induced upregulation of TH protein. NF-κB activator TNF-α increased expression of TH protein. Roles of bilirubin in TH expression and increases in dopamine levels were documented using hyperbilirubinemia rats. Significant increases in dopamine levels, expressions of TH, p65 and p-p65 protein were observed in hyperbilirubinemia rats. Conclusion and Implications BDL significantly increased dopamine levels in rat cortex partly due to bilirubin-mediated TH induction. Increased bilirubin induced TH expression via activating NF-κB signaling pathway.


2009 ◽  
Vol 47 (01) ◽  
Author(s):  
P Nalapareddy ◽  
S Schüngel ◽  
MP Manns ◽  
H Jaeschke ◽  
A Vogel

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