Cadmium induces mitophagy through ROS-mediated PINK1/Parkin pathway

Context and objective: Recent reports have highlighted the relationship between cadmium (Cd) and autophagy, however, whether Cd can activate mitophagy remains enigmatic. This study aims to investigate the effects of Cd on mitophagy and its potential mechanism.

Methods: Mice were intraperitoneally injected with Cd for 3?d. Mitochondrial membrane potential (MMP), mitophagosomes, LC3-II/LC3-I ratio, PINK1 level and mitochondrial mass were evaluated to indicate the effects of Cd on mitophagy. To elucidate the mechanism, reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine (NAC) or acetyl-l-carnitine (ALC) as well as the mitophagy inhibitor cyclosporine A (CsA) were introduced to verify the role of ROS in mitophagy.

Results and conclusions: The results showed that Cd significantly induced MMP collapse and typical mitophagosomes formation, increased LC3-II/LC3-I ratio and PINK1 level, and decreased mitochondrial mass, revealing that Cd could induce mitophagy. However, NAC or ALC pretreatment markedly decreased Cd-induced ROS and simultaneously rescued MMP and mitochondrial mass, suggesting ROS played a crucial role in regulating mitophagy. NAC or ALC also dramatically lessened PINK1 level and mitochondrial accumulation of Parkin, indicating that ROS were related to PINK1/Parkin pathway. Notably, CsA compromised Cd-induced mitophagy, PINK1 accumulation and Parkin translocation while failed to block ROS increase, suggesting ROS functioned as an upstream signal for PINK1/Parkin pathway. Taken together, the results indicated that Cd induced ROS-mediated mitophagy through PINK1/Parkin pathway in kidneys of mice. The present study proposes a new perspective to evaluate the nephrotoxicity and its molecular mechanism under Cd exposure in vivo.     

Study of the mechanism underlying the role of PINK1/Parkin in the formic acid-induced autophagy of PC12 cells

This study aimed to explore PINK1/Parkin's role in methanol metabolite formic acid-induced autophagy in PC12 cells and provide a theoretical basis for elucidating methanol-induced neurotoxicity. After treatment with different formic acid concentrations, we observed the morphology and mitochondria of PC12 cells. We used an ultra-micro enzyme kit to detect the mitochondrial Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities; a JC-1 kit to detect changes in the mitochondrial membrane potential (MMP); MDC staining to detect the autophagy levels; and western blotting to measure the expression levels of the mitochondrial marker protein COX IV and the autophagy-related proteins Beclin1, P62 and LC3II/LC3I, and the mitochondrial and cytoplasmic levels of PINK1, Parkin and P-Parkin. Compared with the control group, the mitochondrial diameters, the mitochondrial Na⁺-K⁺-ATP and Ca²⁺-Mg²⁺-ATPase activities, the MMP, and the COX IV expression levels decreased significantly (P < 0.05). The fluorescence signal intensity (indicating autophagy); relative Beclin1 and LC3II/LC3I protein expression levels; and relative mitochondrial PINK1, Parkin and P-Parkin levels increased significantly, and the relative P62 protein expression levels and relative cytoplasmic PINK1, Parkin and P-Parkin levels decreased significantly (P < 0.05) compared with the control group. Thus, formic acid alters mitochondrial morphology, causes mitochondrial dysfunction, affects the PINK/Parkin pathway and, thus, activates the process of mitochondrial autophagy.     

Resveratrol Protects against Zearalenone-Induced Mitochondrial Defects during Porcine Oocyte Maturation via PINK1/Parkin-Mediated Mitophagy

Mitochondria hold redox homeostasis and energy metabolism as a crucial factor during oocyte maturation, while the exposure of estrogenic mycotoxin zearalenone causes developmental incapacity in porcine oocyte. This study aimed to reveal a potential resistance of phytoalexin resveratrol against zearalenone during porcine oocyte maturation and whether its mechanism was related with PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy. Porcine oocytes were exposed to 20 μM zearalenone with or without 2 μM resveratrol during in vitro maturation. As for the results, zearalenone impaired ultrastructure of mitochondria, causing mitochondrial depolarization, oxidative stress, apoptosis and embryonic developmental incapacity, in which mitophagy was induced in response to mitochondrial dysfunction. Phytoalexin resveratrol enhanced mitophagy through PINK1/Parkin in zearalenone-exposed oocytes, manifesting as enhanced mitophagy flux, upregulated PINK1, Parkin, microtubule-associated protein light-chain 3 beta-II (LC3B-II) and downregulated substrates mitofusin 2 (MFN2), voltage-dependent anion channels 1 (VDAC1) and p62 expressions. Resveratrol redressed zearalenone-induced mitochondrial depolarization, oxidative stress and apoptosis, and accelerated mitochondrial DNA copy during maturation, which improved embryonic development. This study offered an antitoxin solution during porcine oocyte maturation and revealed the involvement of PINK1/Parkin-mediated mitophagy, in which resveratrol mitigated zearalenone-induced embryonic developmental incapacity.     

Garciesculenxanthone B induces PINK1-Parkin-mediated mitophagy and prevents ischemia-reperfusion brain injury in mice

Mitophagy is a selective form of autophagy involving the removal of damaged mitochondria via the autophagy-lysosome pathway.PINK1-Parkin-mediated mitophagy is one of the most important mechanisms in cardiovascular disease,cerebral ischemia-reperfusion(I/R)injury,and neurodegenerative diseases.In this study we conducted an image-based screening in YFP-Parkin HeLa cells to discover new mitophagy regulators from natural xanthone compounds.We found that garciesculenxanthone B(GeB),a new xanthone compound from Garcinia esculenta,induced the formation of YFP-Parkin puncta,a well known mitophagy marker.Furthermore,treatment with GeB dose-dependently promoted the degradation of mitochondrial proteins Tom20,Tim23,and MFN1 in YFP-Parkin HeLa cells and SH-SY5Y cells.We revealed that GeB stabilized PINK1 and triggered Parkin translocation to the impaired mitochondria to induce mitophagy,and these effects were abolished by knockdown of PINK1.Finally,in vivo experiments demonstrated that GeB partially rescued ischemia-reperfusion-induced brain injury in mice.Taken together,our findings demonstrate that the natural compound GeB can promote the PINK1-Parkin-mediated mitophagy pathway,which may be implicated in protection against I/R brain injury.     

小檗碱对心肌缺血再灌注损伤大鼠线粒体自噬及对PINK1/Parkin通路的影响

目的 探讨小檗碱对心肌缺血再灌注损伤大鼠线粒体自噬及PTEN诱导激酶1(PTEN induced putative kinase 1,PINK1)/帕金森病蛋白(Parkin)通路的影响.方法 建立心肌缺血再灌注损伤大鼠模型,随机分组为模型组、小檗碱低、高剂量(75、150 mg/kg)组,自噬抑制剂三甲基腺嘌呤(3-...     

异丙酚对离体大鼠心肌缺血/再灌注损伤的保护作用

目的观察异丙酚对离体大鼠心肌缺血/再灌注损伤的影响并从氧化应激和线粒体介导的凋亡方面探讨其作用机制。方法应用langendorff离体心脏灌注系统建立心肌缺血/再灌注损伤模型。40只SD大鼠随机分为正常对照组、缺血/再灌注模型(I/R)组、异丙酚15、30、60μmol.L-1组。除正常对照外,各组分别平衡灌注20min后,常温全心停灌25min,再灌注30min。Powerlab/8s仪记录各组平衡末、缺血前及再灌30min时的各项心功能指标并测定冠脉流出液中乳酸脱氢酶(LDH)、磷酸肌酸激酶(CK)活性;检测心肌线粒体活力、膜肿胀度、锰超氧化物岐化酶活性(Mn-SOD)和丙二醛(MDA)含量;原位末端转移酶标记法(TUNEL)检测心肌细胞凋亡;流式细胞术检测Bcl-2和Bax的表达,免疫组化法测定天冬氨酸特异的半胱氨酸蛋白酶(Caspase)-3,9,8蛋白的表达。结果与I/R组相比,异丙酚30、60μmol.L-1能明显改善缺血/再灌后的心功能,减弱冠脉流出液中LDH、CK的活性(P<0.05);心肌线粒体活力有所恢复,膜肿胀度减轻,升高Mn-SOD活性,MDA生成明显减少(P<0.05),心肌细胞凋亡明显减少,Bcl-2表达上调,Bax表达下调,Caspase-3,9阳性表达细胞数明显减少(P<0.05)。结论异丙酚明显减轻缺血/再灌所致的心肌线粒体的过氧化损伤,抑制线粒体途径的凋亡,可能是其心肌保护作用机制之一。     

神经细胞凋亡与脑缺血疾病

脑缺血疾病是现代人类健康和生命的主要杀手之一。近年研究发现,神经细胞凋亡是脑缺血疾病造成神经系统损伤的重要机制,神经细胞凋亡通路主要包括线粒体通路、死亡受体通路、PARP/AIF通路。基于神经细胞凋亡与脑缺血损伤关系的深入研究,抗凋亡治疗已经成为了治疗脑缺血疾病的重要途径。     

Exogenous pancreatic kininogenase protects against renal fibrosis in rat model of unilateral ureteral obstruction

Tissue kallikrein has protective function against various types of injury. In this study, we investigated whether exogenous pancreatic kininogenase (PK) conferred renoprotection in a rat model of unilateral ureteral obstruction (UUO) and H₂O₂-treated HK-2 cells in vitro. SD rats were subjected to UUO surgery, then PK (7.2 U/g per day, ip) was administered for 7 or 14 days. After the treatment, rats were euthanized; the obstructed kidneys were harvested for further examination. We found that PK administration significantly attenuated interstitial inflammation and fibrosis, and downregulated the expression of proinflammatory (MCP-1, TLR-2, and OPN) and profibrotic (TGF-β1 and CTGF) cytokines in obstructed kidney. UUO-induced oxidative stress, closely associated with excessive apoptotic cell death and autophagy via PI3K/AKT/FoxO1a signaling, which were abolished by PK administration. We further showed that PK administration increased the expression of bradykinin receptors 1 and 2 (B1R and B2R) mRNA and the production of NO and cAMP in kidney tissues. Coadministration with either B1R antagonist (des-Arg9-[Leu8]-bradykinin) or B2R antagonist (icatibant) abrogated the renoprotective effects of PK, and reduced the levels of NO and cAMP in obstructed kidney. In H₂O₂-treated HK-2 cells, addition of PK (6 pg/mL) significantly decreased ROS production, regulated the expression of oxidant and antioxidant enzymes, suppressed the expression of TGF-β1 and MCP-1, and inhibited cell apoptosis. Our data demonstrate that PK treatment protects against the progression of renal fibrosis in obstructed kidneys.     

Folium Ginkgo extract and tetramethylpyrazine sodium chloride injection (Xingxiong injection) protects against focal cerebral ischaemia/reperfusion injury via activating the Akt/Nrf2 pathway and inhibiting NLRP3 inflammasome activation

ContextFolium Ginkgo extract and tetramethylpyrazine sodium chloride injection (Xingxiong injection) is a compound preparation commonly used for treating cerebral ischaemia/reperfusion injury in ischaemic stroke in China. However, its potential mechanisms on ischaemic stroke remain unknown.ObjectiveThis study explores the potential mechanisms of Xingxiong injection in vivo or in vitro.Materials and methodsSprague-Dawley (SD) rats were randomly assigned to five groups: the sham (normal saline), the model (normal saline) and the Xingxiong injection groups (12.5, 25 or 50 mL/kg). The rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by reperfusion for 14 d. Xingxiong injection was administered via intraperitoneal (i.p.) injection immediately after ischaemia induction for 14 d. Afterwards, rats were sacrificed at 14 d induced by administration of Xingxiong injection.ResultsXingxiong injection significantly reduces infarct volume (23%) and neurological deficit scores (93%) compared with the MCAO/R group. Additionally, Xingxiong injection inhibits the loss in mitochondrial membrane potential (43%) and reduces caspase-3 level (44%), decreases NOX (41%), protein carbonyl (29%), 4-HNE (40%) and 8-OhdG (41%) levels, inhibits the expression of inflammatory factors, such as TNF-α (26%), IL-1β (34%), IL-6 (39%), MCP-1 (36%), CD11a (41%) and ICAM-1 (43%). Moreover, Xingxiong injection can increase p-Akt/Akt (35%) and Nrf2 (47%) protein expression and inhibit NLRP3 (42%) protein expression.ConclusionsXingxiong injection prevents cerebral ischaemia/reperfusion injury via activating the Akt/Nrf2 pathway and inhibiting NLRP3 inflammasome. These findings provide experimental evidence for clinical use of drugs in the treatment of ischaemic stroke.     

血红素加氧酶-1在脑缺血/再灌注损伤中的作用研究

目的探讨血红素加氧酶-1(HO-1)表达和活性变化在脑缺血/再灌注(I/R)致脑损伤中的作用。方法♂小鼠随机分为4组,每组30只。以40g.L-1水合氯醛400mg.kg-1ip麻醉,从颈总静脉抽取并回输约40%总血量加双侧颈总动脉夹闭20min,建立脑I/R损伤模型。3组小鼠于建模前16h分别予以脑室内注射150μmol.L-1氯化正铁血红素(Hemin)、150μmol.L-1锌原卟啉Ⅸ(ZnPPIX)或人工脑脊液(ACSF)3μl/只。假手术组仅麻醉并分离暴露双侧颈总动脉和右侧颈总静脉20min。采用Westernblot法检测海马HO-1蛋白表达;分光光度计法检测海马HO活性和脑黄嘌呤氧化酶(XO)活性及丙二醛(MDA)和活性氧(ROS)含量;TUNEL法检测海马细胞凋亡。结果Hemin组海马HO-1表达明显增强,HO活性升高,脑XO活性、MDA和ROS含量降低,海马神经元凋亡减少(vsACSF,P<0.05);ZnPPIX组海马HO-1表达无变化(vsACSF,P>0.05),HO活性降低,脑XO活性升高伴脑MDA、ROS含量增加及海马神经元凋亡增多(vsACSF,P<0.05)。结论HO-1表达升高对脑I/R致脑损伤具有保护作用,其作用机制与抗脂质过氧化和清除自由基有关。     

Mzb1 protects against myocardial infarction injury in mice via modulating mitochondrial function and alleviating inflammation

Myocardial infarction (MI) leads to the loss of cardiomyocytes, left ventricle dilation and cardiac dysfunction, eventually developing into heart failure. Mzb1 (Marginal zone B and B1 cell specific protein 1) is a B-cell-specific and endoplasmic reticulum-localized protein. Mzb1 is an inflammation-associated factor that participates a series of inflammatory processes, including chronic periodontitis and several cancers. In this study we investigated the role of Mzb1 in experimental models of MI. MI was induced in mice by ligation of the left descending anterior coronary artery, and in neonatal mouse ventricular cardiomyocytes (NMVCs) by H₂O₂ treatment in vitro. We showed that Mzb1 expression was markedly reduced in the border zone of the infarct myocardium of MI mice and in H₂O₂-treated NMVCs. In H₂O₂-treated cardiomyocytes, knockdown of Mzb1 decreased mitochondrial membrane potential, impaired mitochondrial function and promoted apoptosis. On contrary, overexpression of Mzb1 improved mitochondrial membrane potential, ATP levels and mitochondrial oxygen consumption rate (OCR), and inhibited apoptosis. Direct injection of lentiviral vector carrying Len-Mzb1 into the myocardial tissue significantly improved cardiac function and alleviated apoptosis in MI mice. We showed that Mzb1 overexpression significantly decreased the levels of Bax/Bcl-2 and cytochrome c and improved mitochondrial function in MI mice via activating the AMPK-PGC1α pathway. In addition, we demonstrated that Mzb1 recruited the macrophages and alleviated inflammation in MI mice. We conclude that Mzb1 is a crucial regulator of cardiomyocytes after MI by improving mitochondrial function and reducing inflammatory signaling pathways, implying a promising therapeutic target in ischemic cardiomyopathy.     

Neuroprotective activity of Stereospermum suaveolens against global cerebral ischemia rat model

Abstract

Context: Stereospermum suaveolens DC. (Bignoniaceae) is a medicinal tree species native to India. Traditionally, the whole plant is used for various diseases including neuronal disorders.

Objective: The present study evaluated the neuroprotective activity of Stereospermum suaveolens against global cerebral ischemia in a rat model.

Materials and methods: Neuroprotective activity was carried out by global cerebral ischemia on Sprague-Dawley rats and divided into five groups of eight rats each; sham and control groups received normal saline (10?ml/kg) and treated groups received methanol extract of Stereospermum suaveolens (MES) orally (125, 250, and 500?mg/kg) for 10 days prior to the experiment. Global cerebral ischemia was induced by bilateral carotid artery (BCA) occlusion for 30?min followed by 4-h reperfusion. The antioxidant enzymatic and non-enzymatic levels were estimated by UV spectroscopic method along with cerebral infarction area; histopathological studies were carried out.

Results: LD₅₀ of MES was found to be 5000?mg/kg of body weight. The entire test was performed at dose levels 125, 250, and 500?mg/kg of body weight. The results of the study indicate that the Stereospermum suaveolens methanol extract showed neuroprotective activity by a significant decrease in lipid peroxidation (p?<?0.001) and an increase in superoxide dismutase (p?<?0.01), catalase (p?<?0.01), glutathione (p?<?0.001), and total thiol (p?<?0.001) levels in extract-treated groups as compared to control group. Measurement of cerebral infarction area and histopathological studies further supported the protective effect of the extract.

Discussion and conclusion: These findings suggest a potential protective role of Stereospermum suaveolens against global cerebral ischemia/reperfusion-induced brain injury.     

Rutin protects against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion

BACKGROUND AND PURPOSE

Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion.

EXPERIMENTAL APPROACH

We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion (BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses.

KEY RESULTS

BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin.

CONCLUSION AND IMPLICATIONS

Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer''s disease.     

Dual effects of hydrogen sulphide on focal cerebral ischaemic injury via modulation of oxidative stress-induced apoptosis

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和厚朴酚通过抑制脑MPTP开放和调节PARP-1活性保护全脑缺血的作用研究

目的研究和厚朴酚微乳剂对全脑缺血的影响,探讨其可能的作用机制。方法用断头法制备小鼠急性全脑缺血模型;用分光光度法观察脑线粒体通透性转换孔(MPTP)开放程度;用荧光法测定聚腺苷二磷酸核糖聚合酶-1(PARP-1)活性;用MTT法侧细胞活力。结果和厚朴酚(7～70μg.kg-1)单次静注可剂量依赖地增加小鼠断头后喘息次数、降低小鼠脑匀浆液中乳酸的含量,升高脑匀浆液中ATP的含量。和厚朴酚(2.5μmol.L-1～10μmol.L-1)可浓度依赖地降低脑组织MPTP的开放,它可浓度依赖地抑制聚腺苷二磷酸核糖聚合酶(PARP-1)活性,其IC50=76.82μmol.L-1,和厚朴酚可明显提高缺氧损伤的PC12细胞存活率。结论和厚朴酚对全脑缺血有保护作用,该作用与其可能减轻缺血状态、抑制能量耗竭和乳酸堆积有关,可能与抑制神经细胞MPTP开放、抑制PARP-1的活性、从而保护神经细胞有关。这些结果为其治疗全脑缺血提供了实验依据。     

Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in cortical neurons

AIM: To investigate the effect of curcumin on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in rat cortical neurons and to explore the possible mechanism. METHODS: Primary cultured rat cortical neurons wereperformed in vitro and cell viability was measured by MTT assay. DNA fragmentation was used to evaluate cellapoptosis. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (Aψm) was determined by flow cytometric assay. Cellular glutathione (GSH) content was measured by spectrophotometer.‘ Bcl-2family proteins, cytochrome c, cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP) were detected byWestern blot. RESULTS: Exposure of tBHP 100 μmol/L to neurons for 60 rain resulted in △ψm loss and cyto-chrome c release from mitochondria and subsequent activation of caspase-3 and PARP cleavation, and cell apoptosis.After removal of tBHP and then further treatment with curcumin (2.5-20 μmol/L) for 18 h, curcumin abrogated △ψm loss and cytochrome c release, blocked activation of caspase 3, and altered the expression of Bcl-2 family.Further curcumin treatment also prevented cellular GSH and decreased intracellular ROS generation markedly.Curcumin eventually attenuated tBHP-induced apoptosis in cortical neurons. CONCLUSION: Curcumin mayattenuate oxidative damages in cortical neurons by reducing intracellular production of ROS and protecting mito-chondria from oxidative damage.     

An oxovanadium(IV) complex protects murine bone marrow cells against cisplatin-induced myelotoxicity and DNA damage

Cisplatin (CDDP) is one of the first-line anticancer drugs that has gained widespread use against various forms of human malignancies. But, the therapeutic outcome of CDDP therapy is limited due to its adverse effects including myelotoxicity and DNA damage which may lead to the subsequent risk of developing secondary cancer. Hence, in search of a suitable cytoprotectant, this study investigated the probable protective efficacy of an oxovanadium(IV) complex, namely oxovanadium(IV)-L-cysteine methyl ester complex (VC-IV) against CDDP-induced myelosuppression and genotoxic damage in the bone marrow cells of Swiss albino mice. CDDP was administered intraperitoneally (5?mg/kg b.w.) and VC-IV was administered orally (1?mg/kg b.w.) in concomitant and 7 d pretreatment schedule. Treatment with VC-IV in CDDP-treated mice significantly (p?p?p?p?相似文献   

Baicalin protects H9c2 cardiomyocytes against hypoxia/reoxygenation‐induced apoptosis and oxidative stress through activation of mitochondrial aldehyde dehydrogenase 2

Baicalin, a flavonoid glycoside separated from Scutellaria baicalensis, has cardioprotection against ischaemia/reperfusion (I/R) injury. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is considered as an endogenous protective mechanism against I/R injury depending on its anti‐oxidant and anti‐apoptotic characteristics. The present study demonstrates whether ALDH2 contributes to the cardioprotection of baicalin against hypoxia/reoxygenation (H/R)‐inudced H9c2 cardiomyocytes injury. Our results observed that H/R treatment resulted in a significant decrease in cells viability and obvious increases in caspase‐3 activity and apoptosis rate in H9c2 cells, while these alterations were evidently reversed by baicalin pretreatment. Simultaneously, baicalin mitigated H/R‐induced the decreases in the levels of ALDH2 mRNA and protein as well as the activity of ALDH2 in H9c2 cells. However, we found that daidzin, an ALDH2 antagonist, remarkably attenuated baicalin‐elicited inhibitory action on H/R‐induced the downregulation of cells viability and Bcl‐2 protein expression, and the upregulations of caspase‐3 activity, apoptosis rate, cytochrome c and Bax proteins expressions in H9c2 cells. In addition, baicalin reversed H/R‐induced oxidative stress as evidenced by the downregulation of malondialdehyde (MAD) and 4‐hydroxy aldehydes (4‐HNE) levels, the inhibition of endogenous reactive oxygen species (ROS) generation, and the downregulation of superoxide dismutase (SOD) activity induced by H/R treatment, while these effects were also blocked by daidzin. Furthermore, we found that Alda‐1, an ALDH2 agonist, also abolished H/R‐induced cytotoxicity, apoptosis, and oxidative stress, indicating that ALDH2 mediated H/R‐induced H9c2 cell injury. Overall, these results suggested that baicalin prevents H/R‐induced apoptosis and oxidative stress through enhancing ALDH activity and expression in H9c2 cardiomyocytes.     

Thymoquinone protects rat liver after partial hepatectomy under ischaemia/reperfusion through oxidative stress and endoplasmic reticulum stress prevention

Ischaemia reperfusion (I/R) is associated with liver injury and impaired regeneration during partial hepatectomy (PH). The aim of this study was to investigate the effect of thymoquinone (TQ), the active compound of essential oil obtained from Nigella sativa seeds, on rat liver after PH. Male Wistar rats were divided equally into four groups (n = 6) receiving an oral administration of either vehicle solution (sham and PH groups) or TQ at 30 mg/kg (TQ and TQ + PH groups) for 10 consecutive days. Then, rats underwent PH (70%) with 60 minutes of ischaemia followed by 24 hours of reperfusion (PH and TQ + PH groups). Alanine aminotransferase (ALT) activity and histopathological damage were determined. Also, antioxidant parameters, liver regeneration index, hepatic adenosine triphosphate (ATP) content, endoplasmic reticulum (ER) stress and apoptosis were assessed. In response to PH under I/R, liver damage was significantly alleviated by TQ treatment as evidenced by the decrease in ALT activity (P < .01) and histological findings (P < .001). In parallel, TQ preconditioning increased hepatic antioxidant capacities. Moreover, TQ improved mitochondrial function (ATP, P < .05), attenuated ER stress parameters and repressed the expression of apoptotic effectors. Taken together, our results suggest that TQ preconditioning could be an effective strategy to reduce liver injury after PH under I/R. The protective effects were mediated by the increase of antioxidant capacities and the decrease of ER stress and apoptosis.