Dendrobine attenuates isoniazid- and rifampicin-induced liver injury by inhibiting miR-295-5p

2020 ◽  
Vol 39 (12) ◽  
pp. 1671-1680
Author(s):  
R Ci ◽  
K Zhang ◽  
A Zhu ◽  
W Zang
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Luciferase Reporter ◽  
Protective Effects ◽  
Histological Changes ◽  
Stress Markers ◽  
Oxidative Stress Status ◽  
Protein Expressions ◽  
Polymerase Chain ◽  
Underlying Mechanisms

The present study aims to investigate the protective effects of Dendrobine and its underlying mechanisms on liver injury induced by isoniazid (INH) and rifampicin (RIF). A mouse model of liver injury was induced by intragastrically administration of 100 mg/kg INH and 100 mg/kg RIF for 14 days. The mice were intragastrically administrated with Dendrobine (50, 100, and 200 mg/kg) before the administration of INH and RIF. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Oxidative stress markers including glutathione, superoxide dismutase, and malondialdehyde in the liver were measured and liver histopathological examinations were performed. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were applied to determine the mRNA and protein expressions, respectively. Luciferase reporter assay was used to evaluate the interactions between miR-295-5p and CYP1A2. Dendrobine significantly decreased serum ALT and AST and inhibited the liver index and ameliorated the liver histological changes induced by INH and RIF. Besides, Dendrobine also regulated oxidative stress status in the liver by the regulation of CYP1A2. Moreover, mmu-miR-295-5p was identified to target CYP1A2 and to regulate the expression of CYP1A2. In summary, Dendrobine ameliorated INH and RIF induced mouse liver injury by miR-295-5p-mediated CYP1A2 expression.

scholarly journals Grape Seed Procyanidin B2 Protects Porcine Ovarian Granulosa Cells against Oxidative Stress-Induced Apoptosis by Upregulating let-7a Expression

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Jia-Qing Zhang ◽  
Xian-Wei Wang ◽  
Jun-Feng Chen ◽  
Qiao-Ling Ren ◽  
Jing Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Critical Role ◽  
Grape Seed ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Oxidative stress is a causal factor and key promoter of all kinds of reproductive disorders related to granulosa cell (GC) apoptosis that acts by dysregulating the expression of related genes. Various studies have suggested that grape seed procyanidin B2 (GSPB2) may protect GCs from oxidative injury, though the underlying mechanisms are not fully understood. Therefore, whether the beneficial effects of GSPB2 are associated with microRNAs, which have been suggested to play a critical role in GC apoptosis by regulating the expression of protein-coding genes, was investigated in this study. The results showed that GSPB2 treatment protected GCs from a H2O2-induced apoptosis, as detected by an MTT assay and TUNEL staining, and increased let-7a expression in GCs. Furthermore, let-7a overexpression markedly increased cell viability and inhibited H2O2-induced GC apoptosis. Furthermore, the overexpression of let-7a reduced the upregulation of Fas expression in H2O2-treated GCs at the mRNA and protein levels. Dual-luciferase reporter assay results indicated that let-7a directly targets the Fas 3′-UTR. Furthermore, the overexpression of let-7a enhanced the protective effects of GSPB2 against GC apoptosis induced by H2O2. These results indicate that GSPB2 inhibits H2O2-induced apoptosis of GCs, possibly through the upregulation of let-7a.

scholarly journals Resveratrol and Montelukast Alleviate Paraquat-Induced Hepatic Injury in Mice: Modulation of Oxidative Stress, Inflammation, and Apoptosis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Noha A. El-Boghdady ◽  
Nourtan F. Abdeltawab ◽  
Mohammed M. Nooh
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Antioxidant Properties ◽  
Protective Effects ◽  
Serum Total Protein ◽  
Stress Markers ◽  
Group I ◽  
Radical Generation ◽  
Anti Inflammatory ◽  
Induced Apoptosis

Paraquat (PQ) is one of the most used herbicide worldwide. Its cytotoxicity is attributed to reactive radical generation. Resveratrol (Res) and montelukast (MK) have anti-inflammatory and antioxidant properties. The protective effects of Res, MK, or their combination against PQ-induced acute liver injury have not been investigated before. Therefore, we explored the protective potential of Res and/or MK against PQ hepatic toxicity in a mouse model. Mice were randomly assigned to five groups: group I served as the normal control and group II received a single dose of PQ (50 mg/kg, i.p.). Groups III, IV, and V received PQ plus oral Res (5 mg/kg/day), MK (10 mg/kg/day), and Res/MK combination, respectively. Res and/or MK reduced PQ-induced liver injury, evidenced by normalization of serum total protein, ALT, and AST. Res and/or MK significantly reversed PQ-induced oxidative stress markers glutathione and malondialdehyde. Res and/or MK significantly reduced PQ-induced inflammation reflected in TNF-α levels. Furthermore, Res and/or MK reversed PQ-induced apoptosis assessed by differential expression of p53, Bax, and Bcl-2. Histopathologic examination supported the biochemical findings. Although Res and MK displayed antioxidative, anti-inflammatory, and antiapoptotic activities, their combination was not always synergistic.

scholarly journals Allopurinol ameliorates liver injury in type 1 diabetic rats through activating Nrf2

2021 ◽  
Vol 35 ◽  
pp. 205873842110314
Author(s):  
Fei Zeng ◽  
Jierong Luo ◽  
Hong Han ◽  
Wenjie Xie ◽  
Lingzhi Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Caspase 3 ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Liver Protein ◽  
Lipid Peroxidation Product ◽  
Protein Expressions

Hyperglycemia-induced oxidative stress plays important roles in the development of non-alcoholic fatty liver disease (NAFLD), which is a common complication in diabetic patients. The Nrf2-Keap1 pathway is important for cell antioxidant protection, while its role in exogenous antioxidant mediated protection against NAFLD is unclear. We thus, postulated that antioxidant treatment with allopurinol (ALP) may attenuate diabetic liver injury and explored the underlying mechanisms. Control (C) and streptozotocin (STZ)-induced diabetes rats (D) were untreated or treated with ALP for 4 weeks starting at 1 week after diabetes induction. Serum levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), production of lipid peroxidation product malondialdehyde (MDA), and serum superoxide dismutase (SOD) were detected. Liver protein expressions of cleaved-caspase 3, IL-1β, nuclear factor-erythroid-2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), P62, Kelch-like ECH-associated protein 1 (Keap1), and LC3 were analyzed. In vitro, cultured rat normal hepatocytes BRL-3A were grouped to normal glucose (5.5 mM, NG) or high glucose (25 mM, HG) and treated with or without allopurinol (100 µM) for 48 h. Rats in the D group demonstrated liver injury evidenced as increased serum levels of ALT and AST. Diabetes increased apoptotic cell death, enhanced liver protein expressions of cleaved-caspase 3 and IL-1β with concomitantly increased production of MDA while serum SOD content was significantly reduced (all P < 0.05 vs C). In the meantime, protein levels of Nrf2, HO-1, and P62 were reduced while Keap1 and LC3 were increased in the untreated D group as compared to control ( P < 0.05 vs C). And all the above alterations were significantly attenuated by ALP. Similar to our findings obtained from in vivo study, we got the same results in in vitro experiments. It is concluded that ALP activates the Nrf2/p62 pathway to ameliorate oxidative stress and liver injury in diabetic rats.

scholarly journals Green Tea and Epigallocatechin Gallate (EGCG) for the Management of Nonalcoholic Fatty Liver Diseases (NAFLD): Insights into the Role of Oxidative Stress and Antioxidant Mechanism

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1076
Author(s):  
Guoyi Tang ◽  
Yu Xu ◽  
Cheng Zhang ◽  
Ning Wang ◽  
Huabin Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Liver ◽  
Green Tea ◽  
Liver Diseases ◽  
Randomized Clinical Trials ◽  
Epigallocatechin Gallate ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver Diseases ◽  
Underlying Mechanisms

Nonalcoholic fatty liver diseases (NAFLD) represent a set of liver disorders progressing from steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, which induce huge burden to human health. Many pathophysiological factors are considered to influence NAFLD in a parallel pattern, involving insulin resistance, oxidative stress, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammatory cascades, fibrogenic reaction, etc. However, the underlying mechanisms, including those that induce NAFLD development, have not been fully understood. Specifically, oxidative stress, mainly mediated by excessive accumulation of reactive oxygen species, has participated in the multiple NAFLD-related signaling by serving as an accelerator. Ameliorating oxidative stress and maintaining redox homeostasis may be a promising approach for the management of NAFLD. Green tea is one of the most important dietary resources of natural antioxidants, above which epigallocatechin gallate (EGCG) notably contributes to its antioxidative action. Accumulative evidence from randomized clinical trials, systematic reviews, and meta-analysis has revealed the beneficial functions of green tea and EGCG in preventing and managing NAFLD, with acceptable safety in the patients. Abundant animal and cellular studies have demonstrated that green tea and EGCG may protect against NAFLD initiation and development by alleviating oxidative stress and the related metabolism dysfunction, inflammation, fibrosis, and tumorigenesis. The targeted signaling pathways may include, but are not limited to, NRF2, AMPK, SIRT1, NF-κB, TLR4/MYD88, TGF-β/SMAD, and PI3K/Akt/FoxO1, etc. In this review, we thoroughly discuss the oxidative stress-related mechanisms involved in NAFLD development, as well as summarize the protective effects and underlying mechanisms of green tea and EGCG against NAFLD.

scholarly journals Beneficial Effect of Nutrisim© against LPS-Induced Liver Injury: Oxidative Stress Markers and Mitochondrial ATP-ase Activity

2012 ◽  
Vol 7 (1) ◽  
pp. 38-46
Author(s):  
Erandis D. Torres- ◽  
Erika D. Gonzale ◽  
Fermin P. Pacheco ◽  
Rolando Romero-Dav ◽  
Luis A. Romero- ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Beneficial Effect ◽  
Oxidative Stress Markers ◽  
Stress Markers

scholarly journals Protective Effects of Peroxiredoxin 4 (PRDX4) on Cholestatic Liver Injury

2018 ◽  
Vol 19 (9) ◽  
pp. 2509 ◽  
Author(s):  
Jing Zhang ◽  
Xin Guo ◽  
Taiji Hamada ◽  
Seiya Yokoyama ◽  
Yuka Nakamura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Critical Role ◽  
Therapeutic Modality ◽  
Protective Effects ◽  
Fibrotic Liver ◽  
Intrahepatic Bile Ducts ◽  
Duct Ligation ◽  
Cholestatic Liver Injury

Accumulating evidence indicates that oxidative stress plays a critical role in initiating the progression of inflammatory and fibrotic liver diseases, including cholestatic hepatitis. Peroxiredoxin 4 (PRDX4) is a secretory antioxidase that protects against oxidative damage by scavenging reactive oxygen species (ROS) in both the intracellular compartments and extracellular space. In this study, we examined the in vivo net effects of PRDX4 overexpression in a murine model of cholestasis. To induce cholestatic liver injury, we subjected C57BL/6J wild-type (WT) or human PRDX4 (hPRDX4) transgenic (Tg) mice to sham or bile duct ligation (BDL) surgery for seven days. Our results showed that the liver necrosis area was significantly suppressed in Tg BDL mice with a reduction in the severity of liver injuries. Furthermore, PRDX4 overexpression markedly reduced local and systemic oxidative stress generated by BDL. In addition, suppression of inflammatory cell infiltration, reduced proliferation of hepatocytes and intrahepatic bile ducts, and less fibrosis were also found in the liver of Tg BDL mice, along with a reduced mortality rate after BDL surgery. Interestingly, the composition of the hepatic bile acids (BAs) was more beneficial for Tg BDL mice than for WT BDL mice, suggesting that PRDX4 overexpression may affect BA metabolism during cholestasis. These features indicate that PRDX4 plays an important role in protecting against liver injury following BDL and might be a promising therapeutic modality for cholestatic diseases.

Rhizophora Mucronata Lam. (Mangrove) Bark Extract Prevents Ethanol-induced Liver Injury, Oxidative Stress and Apoptosis in Swiss Albino Mice

2021 ◽  
Author(s):  
Chitra Jairaman ◽  
Sabine Matou-Nasri ◽  
Zeyad I Alehaideb ◽  
Syed Ali Mohamed Yacoob ◽  
Anuradha Venkataraman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Histopathological Examination ◽  
Bark Extract ◽  
High Dose ◽  
Protective Effects ◽  
Rhizophora Mucronata ◽  
Ethanol Intoxication ◽  
Hepatoprotective Effects

Abstract The bark extract of Rhizophora mucronata (BERM) was recently reported for its prominent in vitro protective effects against liver cell line toxicity caused by various toxicants, including ethanol. Here, we aimed to verify the in vivo hepatoprotective effects of BERM against ethanol intoxication. An oral administration of different concentrations (100, 200, and 400 mg/kg) of BERM prior to high-dose ethanol via intraperitoneal injection was performed in mice. On the 7th day, liver and kidney sections were dissected out for histopathological examination. The ethanol intoxication caused large areas of liver necrosis while the kidneys were not affected. Pre-BERM administration decreased ethanol-induced liver injury, as compared to the mice treated with ethanol alone. In addition, the pre-BERM administration resulted in a decrement in the level of ethanol-induced oxidative stress, revealed by a concomitant increase of GSH and a decrease of MDA hepatic levels. The BERM extract also reversed the ethanol-induced liver injury and hepatotoxicity, characterized by the low detection of TNF-α gene expression level and fragmented DNA, respectively. Altogether, BERM extract exerts antioxidative activities and present promising hepatoprotective effects against ethanol intoxication. The identification of the related bioactive compounds will be of interest for future use at physiological concentrations in ethanol-intoxicated individuals.

Protective effects of deferoxamine on lead-induced cardiotoxicity in rats

2020 ◽  
Vol 36 (10) ◽  
pp. 800-806
Author(s):  
Alireza Gazeri ◽  
Azadeh Aminzadeh
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Chelating Agent ◽  
Industrial Applications ◽  
Protective Effects ◽  
Industrialized Countries ◽  
Protective Capacity ◽  
Cardiac Tissues ◽  
Stress Markers ◽  
Total Antioxidant

Because of the numerous industrial applications of lead (Pb), Pb poisoning is an important public health threat in the world particularly in developing and industrialized countries. Oxidative stress is one of the important mechanisms of Pb-mediated toxicity. Deferoxamine (DFO) is an iron chelating agent that has recently shown antioxidant and antiapoptotic effects. This study investigated the protective capacity of DFO against Pb-induced cardiotoxicity in rats. We used five groups in this study: control, DFO (300 mg/kg), Pb (50 mg/kg), DFO (150 mg/kg) + Pb, DFO (300 mg/kg) + Pb. DFO was administered intraperitoneally 30 min before intraperitoneal injection of Pb for 5 days. After drug treatment, the levels of lactate dehydrogenase (LDH), lipid peroxidation (LPO), glutathione (GSH), and antioxidant enzymes were measured in serum and heart samples. The results showed that pretreatment with DFO reduced Pb-induced oxidative stress markers in serum and cardiac tissues. We found that LDH and LPO levels were significantly increased in Pb-treated rats and decreased with DFO pre-administration. Furthermore, the decreased activities of total antioxidant capacity, and GSH were observed after Pb treatment. However, DFO administration effectively prevented the Pb-induced alterations of these antioxidant enzymes activities. In conclusion, the results presented here indicate that DFO has protective effects in Pb-induced cardiotoxicity in rats, probably due to its antioxidant action and inhibition of oxidative stress.

scholarly journals A Discovery of Relevant Hepatoprotective Effects and Underlying Mechanisms of Dietary Clostridium butyricum Against Corticosterone-Induced Liver Injury in Pekin Ducks

2019 ◽  
Vol 7 (9) ◽  
pp. 358 ◽  
Author(s):  
Yanhan Liu ◽  
Cun Liu ◽  
Liqing Huang ◽  
Zhaofei Xia
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Basal Diet ◽  
Clostridium Butyricum ◽  
Pekin Ducks ◽  
Injury Model ◽  
Hepatoprotective Effects ◽  
Underlying Mechanisms

Clostridium butyricum (C. butyricum) can attenuate oxidative stress, inflammation, and hepatic fatty deposition in poultry, however, the underlying mechanisms for this in Pekin ducks remain unclear. This study evaluated these hepatoprotective effects and the underlying mechanisms in a corticosterone (CORT)-induced liver injury model in Pekin ducks fed a C. butyricum intervention diet. A total of 500 Pekin ducks were randomly divided into five groups: one group (CON group) was only provided with a basal diet, three groups were provided a basal diet with 200 mg/kg (LCB group), 400 mg/kg (MCB group), or 600 mg/kg (HCB group) C. butyricum, respectively, and one group was provided a basal diet with 150 mg/kg aureomycin (ANT group) for 42 d. At 37 days-old, all ducks received daily intraperitoneal injections of CORT for five days to establish a liver injury model. C. butyricum intervention alleviated liver injury by decreasing the liver organ indices, hepatic steatosis and hepatocyte necrosis, and improving liver function, antioxidant capacity, and inflammatory factors. Hepatic RNA-seq revealed 365 differentially expressed genes (DEGs) between the MCB and CON groups, with 229 up- and 136 down-regulated DEGs in the MCB group. Between the MCB and ANT groups, 407 DEGs were identified, including 299 up- and 108 down-regulated genes in MCB group. Some DEGs in the MCB group related to oxidative stress and inflammatory responses such as Sod3, Tlr2a/b, and Il10, which were up-regulated, while Apoa1, Cyp7a1, Acsl1/5, Fasn, Ppar-γ, and Scd, which are involved in lipid metabolism, were down-regulated, indicating that these genes were responsive to dietary C. butyricum for the alleviation of corticosterone-induced hepatic injury. Toll-like receptor signaling, PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction, peroxisome proliferator-activated receptor (PPAR) signaling pathway, adipocytokine and glycerophospholipid metabolism signaling pathway were significantly enriched in the MCB group. These findings indicate that C. butyricum intervention can protect Pekin ducks from corticosterone-induced liver injury by the modulation of immunoregulatory- and lipid metabolism-related genes and pathways.

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