scholarly journals Protective Effects and Mechanisms of Dendrobium nobile Lindl. Alkaloids on PC12 Cell Damage Induced by Aβ25-35

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yuan Liu ◽  
Tingting Pi ◽  
Xiaohui Yang ◽  
Jingshan Shi
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cell ◽  
Caspase 3 ◽  
Cell Damage ◽  
Protective Effects ◽  
Related Protein ◽  
Caspase 9 ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Dendrobium Nobile Lindl

Background. Aβ deposition abnormally in the mitochondria can damage the mitochondrial respiratory chain and activate the mitochondrial-mediated apoptosis pathway, resulting in AD-like symptoms. Objective. To observe the protective effects of Dendrobium nobile Lindl. alkaloids (DNLA) on Aβ25-35-induced oxidative stress and apoptosis in PC12 cells explore its possible protective mechanisms. Methods. PC12 cells were treated with DNLA with different concentrations (0.035 mg/L, 0.3 mg/L, and 3.5 mg/L) for 6 h, followed by administration with Aβ25-35 (10 μM) for 24 h. MTT assay and flow cytometer observe the effect of DNLA on Aβ25-35-induced cytotoxicity and apoptosis of PC12 cell. Based on the mitochondrial apoptosis pathway to study the antiapoptotic effect of DNLA on this model and its relationship with oxidative stress, flow cytometer detected the level of reactive oxygen species (ROS), and ELISA kits were used to detect superoxide dismutase activity (SOD) and glutathione (GSH) content in cells. The JC-1 fluorescent staining observed the effect of DNLA on the mitochondrial membrane potential (MMP) with inverted immunofluorescence microscopy. Western blot was used to detect the levels of mitochondrial apoptosis pathway-related protein and its major downstream proteins Bax, Bcl-2, cleaved-caspase-9, and cleaved-caspase-3. Results. DNLA can significantly improve the viability and apoptosis rate of PC12 cell damage induced by Aβ25-35. It also can restore the reduced intracellular ROS content and MMP, while SOD activity and GSH content increase significantly. The expression of apoptosis-related protein Bax, cleaved-caspase-9, and cleaved-caspase-3 decreased when the Bcl-2 protein expression was significantly increased. Conclusion. These findings suggest that it can significantly inhibit the apoptosis of PC12 cell damage induced by Aβ25-35. The mechanism may reduce the level of cellular oxidative stress and thus inhibit the mitochondrial-mediated apoptosis pathway.

scholarly journals Protective Effect of N-Acetylcysteine against Oxidative Stress Induced by Zearalenone via Mitochondrial Apoptosis Pathway in SIEC02 Cells

Toxins ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 407 ◽  
Author(s):  
Jingjing Wang ◽  
Mengmeng Li ◽  
Wei Zhang ◽  
Aixin Gu ◽  
Jiawen Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Messenger Rna ◽  
Caspase 3 ◽  
Intestinal Epithelial ◽  
Mitochondrial Apoptosis ◽  
Caspase 9 ◽  
Treatment Results ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Small Intestinal

Zearalenone (ZEN), a nonsteroidal estrogen mycotoxin, is widely found in feed and foodstuffs. Intestinal cells may become the primary target of toxin attack after ingesting food containing ZEN. Porcine small intestinal epithelial (SIEC02) cells were selected to assess the effect of ZEN exposure on the intestine. Cells were exposed to ZEN (20 µg/mL) or pretreated with (81, 162, and 324 µg/mL) N-acetylcysteine (NAC) prior to ZEN treatment. Results indicated that the activities of glutathione peroxidase (Gpx) and glutathione reductase (GR) were reduced by ZEN, which induced reactive oxygen species (ROS) and malondialdehyde (MDA) production. Moreover, these activities increased apoptosis and mitochondrial membrane potential (ΔΨm), and regulated the messenger RNA (mRNA) expression of Bax, Bcl-2, caspase-3, caspase-9, and cytochrome c (cyto c). Additionally, NAC pretreatment reduced the oxidative damage and inhibited the apoptosis induced by ZEN. It can be concluded that ZEN-induced oxidative stress and damage may further induce mitochondrial apoptosis, and pretreatment of NAC can degrade this damage to some extent.

scholarly journals MiR-122 Participates in Oxidative Stress and Apoptosis in STZ-Induced Pancreatic β Cells by Regulating PI3K/AKT Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jing Wang ◽  
Zhichun Dong ◽  
Liyin Lou ◽  
Lijuan Yang ◽  
Jingying Qiu
Keyword(s):  
Oxidative Stress ◽  
Insulin Secretion ◽  
Caspase 3 ◽  
Cell Damage ◽  
Caspase 9 ◽  
Intracellular Ros ◽  
Reverse Transcription Quantitative Pcr ◽  
Apoptosis Detection ◽  
Dichlorofluorescein Diacetate ◽  
And Oxidative Stress

At present, there are few reports concerning the relationship between miR-122 and diabetes. In addition, the effect of miR-122 on streptozotocin- (STZ-) induced oxidative damage in INS-1 cells remains unclear. The present study aimed to investigate the role and modulatory mechanisms involving miR-122 in diabetes. STZ was used to induce INS-1 cell damage. Reverse transcription-quantitative PCR was used to investigate the expression of miR-122. A TUNEL cell apoptosis detection kit was used to detect apoptosis. Intracellular ROS levels were determined using dichlorofluorescein-diacetate. The activities of insulin secretion, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-px) were measured using ELISA kits. Western blotting was used to measure the expression levels of Bax, Bcl-2, PI3K, p-PI3K, caspase-3 and caspase-9, cleaved-caspase-3 and cleaved-caspase-9, AKT, and p-AKT. Then, LY294002 (LY, PI3K inhibitor) was used to treat INS-1 cells, and oxidative stress and apoptosis were measured. The results showed that STZ-induced inhibitory effects on insulin secretion were mitigated by miR-122 inhibitor, and the activities of SOD, CAT, and GSH-px were also increased. Furthermore, miR-122 inhibitor inhibited apoptosis and oxidative stress in STZ-induced INS-1 cells. Finally, the addition of LY increased insulin levels; reduced the activities of SOD, CAT, and GSH-px; and promoted apoptosis in STZ-induced INS-1 cells. In conclusion, interference with miR-122 can inhibit oxidative stress and apoptosis in STZ-induced INS-1 cells, involving a mechanism of action related to the PI3K/AKT pathway.

scholarly journals The Protective Effects of α-Mangostin Attenuate Sodium Iodate-Induced Cytotoxicity and Oxidative Injury via Mediating SIRT-3 Inactivation via the PI3K/AKT/PGC-1α Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1870
Author(s):  
Chen-Ju Chuang ◽  
Meilin Wang ◽  
Jui-Hsuan Yeh ◽  
Tzu-Chun Chen ◽  
Shang-Chun Tsou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Cell Damage ◽  
Outer Nuclear Layer ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Dependent Manner ◽  
Protective Effects ◽  
Age Related

It is well known that age-related macular degeneration (AMD) is an irreversible neurodegenerative disease that can cause blindness in the elderly. Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is a part of the pathogenesis of AMD. In this study, we evaluated the protective effect and mechanisms of alpha-mangostin (α-mangostin, α-MG) against NaIO3-induced reactive oxygen species (ROS)-dependent toxicity, which activates apoptosis in vivo and in vitro. MTT assay and flow cytometry demonstrated that the pretreatment of ARPE-19 cells with α-MG (0, 3.75, 7.5, and 15 μM) significantly increased cell viability and reduced apoptosis from NaIO3-induced oxidative stress in a concentration-dependent manner, which was achieved by the inhibition of Bax, cleaved PARP-1, cleaved caspase-3 protein expression, and enhancement of Bcl-2 protein. Furthermore, pre-incubation of ARPE-19 cells with α-MG markedly inhibited the intracellular ROS and extracellular H2O2 generation via blocking of the abnormal enzyme activities of superoxide dismutase (SOD), the downregulated levels of catalase (CAT), and the endogenous antioxidant, glutathione (GSH), which were regulated by decreasing PI3K-AKT-PGC-1α-STRT-3 signaling in ARPE-19 cells. In addition, our in vivo results indicated that α-MG improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer by inhibiting the expression of cleaved caspase-3 protein. Taken together, our results suggest that α-MG effectively protects human ARPE-19 cells from NaIO3-induced oxidative damage via antiapoptotic and antioxidant effects.

scholarly journals DIHYDROMYRICETIN ATTENUATES HIGH GLUCOSE-INDUCED CASPASE 3 EXPRESSION, ROS PRODUCTION AND INCREASES AMPK PHOSPHONYLATION IN PC12 CELLS

2019 ◽  
Vol 8 (5) ◽  
Author(s):  
Shuo Wang ◽  
Lin Wang ◽  
Haijian Li ◽  
Shumei Wang ◽  
Zhenzhen Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Caspase 3 ◽  
Cell Damage ◽  
Neural Function ◽  
Ros Production ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Central Nervous System Dysfunction ◽  
Amp Activated Protein Kinase

Dihydromyricetin (DMY) has a protective effect on neural function under central nervous system dysfunction conditions. There is growing interest concerning the beneficial effects of DMY on treating diabetic neuropathy (DN). This study was carried to detect protective effects of DMY on high glucose (HG)-induced cell damage and related mechanisms. The effect of DMY on cell survival was detected by MTT assay. Caspase-3 and phosphorylated AMP-activated protein kinase (AMPK) was evaluated by Western blotting. The effects of DMY and AMPK agonist AICAR on ROS production was determined. Our results showed that DMY treatment protect against HG-induced cell damage. DMY treatment significantly reduced the expression of caspase-3 and phosphorylated AMPK. ROS production was inhibited by DMY or AMPK agonist AICAR treatment. These studies demonstrate that DMY may inhibit ROS production, caspase-3 expression through AMPK pathway. Keywords: dihydromyricetin, caspase, oxidative stress

Protective effect of dexmedetomidine on neuronal hypoxic injury through inhibition of miR-134

2021 ◽  
pp. 096032712110237
Author(s):  
Y-J Li ◽  
D-Z Zhang ◽  
Y Xi ◽  
C-A Wu
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Pc12 Cells ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Cell Damage ◽  
Annexin V ◽  
Protective Effects ◽  
Gene And Protein Expression ◽  
And Oxidative Stress

Objective: To explore the mechanism of dexmedetomidine (DEX)-mediated miR-134 inhibition in hypoxia-induced damage in PC12 cells. Methods: Hydrogen peroxide (H2O2)-stimulated PC12 cells were divided into control, H2O2, DEX + H2O2, miR-NC/inhibitor + H2O2, and miR-NC/ mimic + DEX + H2O2 groups. Cell viability and apoptosis were assessed by the 3-(4,5-dimethylthiazol(-2-y1)-2,5-diphenytetrazolium bromide (MTT) assay and Annexin V-FITC/PI staining, while gene and protein expression levels were detected by qRT-PCR and western blotting. Reactive oxygen species (ROS) levels were tested by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining, and malondialdehyde (MDA) content was determined with a detection kit. Results: DEX treatment decreased H2O2-elevated miR-134 expression. H2O2-induced PC12 cell damage was improved by DEX and miR-134 inhibitor; additionally, cell viability was increased, while cell apoptosis was reduced. In addition, both DEX and miR-134 inhibitor reduced the upregulated expression of cleaved caspase-3 and increased the downregulated expression of Bcl-2 in H2O2-induced PC12 cells. However, compared to that in the DEX + H2O2 group, cell viability in the mimic + DEX + H2O2 group was decreased, and the apoptotic rate was elevated with increased cleaved caspase-3 and decreased Bcl-2 expression. Inflammation and oxidative stress were increased in H2O2-induced PC12 cells but improved with DEX or miR-134 inhibitor treatment. However, this improvement of H2O2-induced inflammation and oxidative stress induced by DEX in PC12 cells could be reversed by the miR-134 mimic. Conclusion: DEX exerts protective effects to promote viability and reduce cell apoptosis, inflammation, and oxidative stress in H2O2-induced PC12 cells by inhibiting the expression of miR-134.

scholarly journals Antiepileptic Effects of Protein-Rich Extract from Bombyx batryticatus on Mice and Its Protective Effects against H2O2-Induced Oxidative Damage in PC12 Cells via Regulating PI3K/Akt Signaling Pathways

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Meibian Hu ◽  
Yujie Liu ◽  
Liying He ◽  
Xing Yuan ◽  
Wei Peng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Signaling Pathways ◽  
Pc12 Cells ◽  
Caspase 3 ◽  
Akt Signaling ◽  
Maximal Electroshock ◽  
Protective Effects ◽  
Caspase 9 ◽  
Protein Rich

Bombyx batryticatus is a known traditional Chinese medicine (TCM) utilized to treat convulsions, epilepsy, cough, asthma, headaches, and purpura in China for thousands of years. This study is aimed at investigating the antiepileptic effects of protein-rich extracts from Bombyx batryticatus (BBPs) on seizure in mice and exploring the protective effects of BBPs against H2O2-induced oxidative stress in PC12 cells and their underlying mechanisms. Maximal electroshock-induced seizure (MES) and pentylenetetrazole- (PTZ-) induced seizure in mice and the histological analysis were carried out to evaluate the antiepileptic effects of BBPs. The cell viability of PC12 cells stimulated by H2O2 was determined by MTT assay. The apoptosis and ROS levels of H2O2-stimulated PC12 cells were determined by flow cytometry analysis. Furthermore, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), lactate dehydrogenase (LDH), and glutathione (GSH) in PC12 cells were assayed by ELISA and expressions of caspase-3, caspase-9, Bax, Bcl-2, PI3K, Akt, and p-Akt were evaluated by Western blotting and quantitative real-time polymerase chain reaction (RT-qPCR) assays. The results revealed that BBPs exerted significant antiepileptic effects on mice. In addition, BBPs increased the cell viability of H2O2-stimulated PC12 cells and reduced apoptotic cells and ROS levels in H2O2-stimulated PC12 cells. By BBPs treatments, the levels of MDA and LDH were reduced and the levels of SOD and GSH-Px were increased in H2O2-stimulated PC12 cells. Moreover, BBPs upregulated the expressions of PI3K, Akt, p-Akt, and Bcl-2, whereas they downregulated the expressions of caspase-9, caspase-3, and Bax in H2O2-stimulated PC12 cells. These findings suggested that BBPs possessed potential antiepileptic effects on MES and PTZ-induced seizure in mice and protective effects on H2O2-induced oxidative stress in PC12 cells by exerting antioxidative and antiapoptotic effects via PI3K/Akt signaling pathways.

scholarly journals Modulations of Histone Deacetylase 2 Offer a Protective Effect through the Mitochondrial Apoptosis Pathway in Acute Liver Failure

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Yao Wang ◽  
Fan Yang ◽  
Fang-Zhou Jiao ◽  
Qian Chen ◽  
Wen-Bin Zhang ◽  
...  
Keyword(s):  
Liver Failure ◽  
Histone Deacetylase ◽  
Liver Tissue ◽  
Caspase 3 ◽  
Mitochondrial Apoptosis ◽  
Caspase 9 ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Histone Deacetylase 2 ◽  
Cyt C

The purpose of this study was to investigate the modulation of histone deacetylase 2 (HDAC2) on mitochondrial apoptosis in acute liver failure (ALF). The cellular model was established with LO2 cells stimulated by tumor necrosis factor alpha (TNF-α)/D-galactosamine (D-gal). Rats were administrated by lipopolysaccharide (LPS)/D-gal as animal model. The cell and animal models were then treated by HDAC2 inhibitor CAY10683. HDAC2 was regulated up or down by lentiviral vector transfection in LO2 cells. The mRNA levels of bcl2 and bax were detected by real-time PCR. The protein levels of HDAC2, bcl2, bax, cytochrome c (cyt c) in mitochondrion and cytosol, apoptosis protease activating factor 1 (apaf1), caspase 3, cleaved-caspase 3, caspase 9, cleaved-caspase 9, acetylated histone H3 (AH3), and histone H3 (H3) were assayed by western blot. Apoptosis was detected by flow cytometry. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) levels were also assayed. The openness degree of the mitochondrial permeability transition pore (MPTP) was detected by ultraviolet spectrophotometry. The apoptosis of hepatocytes in liver tissues was determined by tunnel staining. The liver tissue pathology was detected by hematoxylin eosin (HE) staining. The ultrastructure of liver tissue was observed by electron microscopy. Compared with cell and rat model groups, the bax mRNA level was decreased, and bcl2 mRNA was increased in the CAY10683 treatment group. The protein levels of HDAC2, bax, cyt c in cytosol, apaf1, cleaved-caspase 3, and cleaved-caspase 9 were decreased, and the apoptosis rate was decreased (P<0.05), whereas the protein level of bcl2 and cyt c in the mitochondrion was elevated (P<0.05) in the CAY10683 treatment group. In the HDAC2 down- or upregulated LO2 cells, the mitochondrial apoptosis pathway was inhibited or activated, respectively. After being treated with TNF-α/D-gal in HDAC2 down- or upregulated LO2 cells, the mitochondrial apoptosis pathway was further suppressed or activated, respectively. The MPTP value was elevated in CAY10683-treated groups compared with the rat model group (P<0.05). Liver tissue pathological damage and apoptotic index in the CAY10683-treated group were significantly reduced. In addition, AH3 was elevated in both cell and animal model groups (P<0.05). Downregulated or overexpressed HDAC2 could accordingly increase or decrease the AH3 level, and TNF-α/D-gal could enhance the acetylation effect. These results suggested that modulations of histone deacetylase 2 offer a protective effect through the mitochondrial apoptosis pathway in acute liver failure.

Neuroprotective Effects of Extracts from the Radix Curcuma aromatica on H2O2-induced Damage in PC12 Cells

2018 ◽  
Vol 21 (8) ◽  
pp. 571-582 ◽  
Author(s):  
Juxiang Liu ◽  
Lianli Zhang ◽  
Dan Liu ◽  
Baocai Li ◽  
Mi Zhang
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Caspase 3 ◽  
Cell Damage ◽  
Positive Control ◽  
Neuroprotective Activity ◽  
Antioxidant Enzyme Activities ◽  
Morphologic Change ◽  
Neuroprotective Effects ◽  
Etoh Extract

Aim & Objectives: Curcuminoids are characteristic constituents in Curcuma, displaying obviously neuroprotective activities against oxidative stress. As one of the Traditional Chinese Medicines from Curcuma, the radix of Curcuma aromatica is also rich in those chemicals, but its neuroprotective activity and mechanism remain unknown. The aim of the current study is to evaluate the neuroprotective effects of extracts from the radix of C. aromatica (ECAs) on H2O2-damaged PC12 cells. Material and Methods: The model of oxidative stress damage was established by treatment of 400 µM H2O2 on PC12 to induce cell damage. After the treatment of ECWs for 24 h, the cell viability, LDH, SOD, CAT and GSH were measured to evaluate the neuroprotection of ECAs on that model. The potential action mechanism was studied by measurement of level of ROS, cell apoptosis rate, mitochondrial membrane potential (MMP), morphologic change, the intracellular Ca2+ content (F340/F380) and the expressions of Bcl-2, Bax and Caspase-3. Additionally, the constituents from tested extracts were analyzed by HPLC-DAD-Q-TOF-MS method. Results: Compared with a positive control, Vitamin E, 10 µg/ml of 95% EtOH extract (HCECA) and 75% EtOH extract (MCECA) can markedly increase the rate of cell survival and enhance the antioxidant enzyme activities of SOD, CAT, increase the levels of GSH, decrease LDH release and the level of ROS, attenuate the intracellular Ca2+ overloading, reduce the cell apoptotic rate and stabilize MMP, down-regulate Bcl-2 expression, up-regulate Bax and caspase-3 expression, and improve the change of cell morphology. The chemical analysis showed that diarylheptanoids and sesquiterpenoids are the major chemicals in tested extracts and the former were richer in HCECA and MCECA than others. Conclusions: These findings indicated that the effects of HCECA and MCECA on inhibiting the cells damage induced by H2O2 in PC12 are better than other extracts from the radix of C. aromatica, and the active constituents with neuroprotective effects consisting in those two active extracts are diarylheptanoids.

scholarly journals Ethanol Extract of Maclura tricuspidata Fruit Protects SH-SY5Y Neuroblastoma Cells against H2O2-Induced Oxidative Damage via Inhibiting MAPK and NF-κB Signaling

2021 ◽  
Vol 22 (13) ◽  
pp. 6946
Author(s):  
Weishun Tian ◽  
Suyoung Heo ◽  
Dae-Woon Kim ◽  
In-Shik Kim ◽  
Dongchoon Ahn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Oxidative Damage ◽  
Cell Damage ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Biologically Active ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Neuroprotective Effects

Free radical generation and oxidative stress push forward an immense influence on the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Maclura tricuspidata fruit (MT) contains many biologically active substances, including compounds with antioxidant properties. The current study aimed to investigate the neuroprotective effects of MT fruit on hydrogen peroxide (H2O2)-induced neurotoxicity in SH-SY5Y cells. SH-SY5Y cells were pretreated with MT, and cell damage was induced by H2O2. First, the chemical composition and free radical scavenging properties of MT were analyzed. MT attenuated oxidative stress-induced damage in cells based on the assessment of cell viability. The H2O2-induced toxicity caused by ROS production and lactate dehydrogenase (LDH) release was ameliorated by MT pretreatment. MT also promoted an increase in the expression of genes encoding the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). MT pretreatment was associated with an increase in the expression of neuronal genes downregulated by H2O2. Mechanistically, MT dramatically suppressed H2O2-induced Bcl-2 downregulation, Bax upregulation, apoptotic factor caspase-3 activation, Mitogen-activated protein kinase (MAPK) (JNK, ERK, and p38), and Nuclear factor-κB (NF-κB) activation, thereby preventing H2O2-induced neurotoxicity. These results indicate that MT has protective effects against H2O2-induced oxidative damage in SH-SY5Y cells and can be used to prevent and protect against neurodegeneration.

scholarly journals Modulatory effect of Persea Americana oil against diethylnitrosamine-induced hepatotoxicity in rats: a proposed mechanism

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Omayma A. R. Abozaid ◽  
Lobna M. Anees ◽  
Gehan R. Abdel-Hamed
Keyword(s):  
Nadph Oxidase ◽  
Caspase 3 ◽  
Persea Americana ◽  
Gene Expressions ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Apoptotic Effect ◽  
Oxide Synthase ◽  
Parp 1 ◽  
Inducible Nitric Oxide

Abstract Background The purpose of this study was to investigate the effectiveness of Persea Americana (avocado) oil against diethylnitrosamine (DEN)-induced hepatotoxicity in rats. Methods For the induction of hepatotoxicity, DEN was administrated orally in a dose of 20 mg/kg B.wt for 6 successive weeks, and then the animals were gavaged with Persea Americana oil in a dose of 4 mL/kg b.wt. daily for another 6 weeks. Serum caspase-3 activity and poly (ADP-ribose) polymerase-1 (PARP-1) levels were estimated; in addition to gene expressions for NADPH oxidase, inducible nitric oxide synthase (iNOS), Bcl-2, and Bax were detected. Results The DEN-intoxicated group exhibited a remarkable increase in NADPH oxidase and iNOS expression combined with over-activation of PARP-1 and increased antiapoptotic Bcl-2 gene expression, whereas the expression of apoptotic biomarkers significantly decreased. On the other hand, treatment with Persea Americana oil significantly suppressed the elevated levels of hepatic enzymes and improved histopathological alterations in the liver. Furthermore, these groups displayed marked downregulation in NADPH oxidase and iNOS expressions. Persea Americana oil suppressed the expression of the antiapoptotic Bcl-2, activated the intrinsic mitochondrial apoptosis pathway through upregulation of pro-apoptotic Bax, and induced an obvious increase in caspase-3 activity. Moreover, Persea Americana oil administration markedly inhibited the activity of PARP-1. Conclusions This study indicated the promising potential of Persea Americana oil against DEN-induced hepatic injury through its anti-oxidative activity and pro-apoptotic effect via caspase activation and PARP-1 inhibition.

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