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Physiological and cellular mechanisms of ischemic preconditioning microRNAs-mediated in underlying of ischemia/reperfusion injury in different organs

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MOLECULAR AND CELLULAR BIOCHEMISTRY 2025年第2期480卷 855-868页

作者： Gheitasi, Izadpanah akbari, ghaidafeh Savari, Feryal Yasuj Univ Med Sci Fac Med Dept Physiol Yasuj Iran Shoushtar Fac Med Sci Dept Med Basic Sci Shoushtar Iran

Ischemia-reperfusion (I/R) injury, as a pathological phenomenon, takes place when blood supply to an organ is disrupted and then aggravated during restoration of blood flow. Ischemic preconditioning (IPC) is a potent method for attenuating subsequent events of IR damage in numerous organs. IPC protocol is determined by a brief and sequential time periods of I/R before the main ischemia. MicroRNAs are endogenous non-coding RNAs that regulate post-transcriptionally target mRNA translation via degrading it and/or suppressing protein synthesis. This review introduces the physiological and cellular mechanisms of ischemic preconditioning microRNAs-mediated after I/R insult in different organs such as the liver, kidney, heart, brain, and intestine. Data of this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, Web of Science, and Scientific Information Database from 2000 to 2023. Based on these literature studies, IPC/IR intervention can affect cellular mechanisms including oxidative stress, apoptosis, angiogenesis, and inflammation through up-regulation or down-regulation of multiple microRNAs and their target genes.

关键词： Ischemia/reperfusion injury Ischemic preconditioning MicroRNAs

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Evaluation of the Effect of Finasteride and Tamsulosin on Glucose, Lipid, and Oxidative Stress Factors of Patients with Benign Prostatic Hyperplasia

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SN Comprehensive Clinical Medicine 2025年第1期7卷 1-6页

作者： Sedaghattalab, Moslem akbari, ghaidafeh Malekzadeh, Mohammad Doustimotlagh, Amirhossein Rabani, Seyed Mohammadreza Mehrabi, Saeid Department of Internal Medicine Yasuj University of Medical Sciences Yasuj Iran Medicinal Plants Research Center Yasuj University of Medical Sciences Yasuj Iran Social Determinants of Health Research Center Yasuj University of Medical Sciences Yasuj Iran Department of Clinical Biochemistry Faculty of Medicine Yasuj University of Medical Sciences Yasuj Iran Cellular and Molecular Research Center Yasuj University of Medical Sciences Yasuj Iran

Benign prostatic hyperplasia (BPH) is a common disorder which affects 25–60% of men throughout their life. The most common BPH medical management consist of finasteride and tamsulosin. Some studies show the increasing risk of metabolic syndrome following BPH drug administration. Thus, we decided to evaluate serum lipid, glucose profile, and oxidative stress markers among BPH patients who received tamsulosin alone and in combination with finasteride. Seventy patients with BPH were referred to lab department to determine their baseline metabolic parameters and serum oxidative/inflammatory markers. Then, randomly divided into two groups including tamsulosin, 0.4 mg daily, orally, and tamsulosin 0.4 mg + finasteride 5 mg daily, orally. Following 6 months, blood sampling was done again for evaluation of previous markers. Data obtained from before and after the intervention were analyzed and p < 0.05 considered significant level. After 6 months of tamsulosin treatment, we demonstrated a significant elevation in fasting blood sugar (FBS), triglyceride (TG), cholesterol, and low-density lipoprotein (LDL). Combination therapy with tamsulosin and finasteride significantly increased serum profile of FBS, TG, cholesterol, and LDL and decreased serum levels of malondialdehyde (MDA), high-density lipoprotein (HDL), glutathione peroxidase (GPx), and ferric reducing antioxidant power (FRAP) after the intervention. This study showed that treating of BPH patients with tamsulosin alone and in combination with finasteride could disturb in serum glucose and lipid profile. Physicians should consider these complications in the follow-up of their patients when prescribed of these drugs.

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Emerging roles of microRNAs in intestinal ischemia/reperfusion-induced injury: a review

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JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY 2020年第4期76卷 525-537页

作者： akbari, ghaidafeh Yasuj Univ Med Sci Sch Med Dept Physiol Med Plants Res Ctr Yasuj Iran

Intestinal ischemia/reperfusion (II/R) injury is a serious pathological phenomenon in underlying hemorrhagic shock, trauma, strangulated intestinal obstruction, and acute mesenteric ischemia which associated with high morbidity and mortality. MicroRNAs (miRNAs, miRs) are endogenous non-coding RNAs that regulate post-transcriptionally target mRNA translation via degrading it and/or suppressing protein synthesis. This review discusses on the role of some miRNAs in underlying II/R injury. Some of these miRNAs can have protective action through agomiR or specific antagomiR, and others can have destructive effects in the basal level of II/R insult. Based on these literature reviews, II/R injury affects several miRNAs and their specific target genes. Some miRNAs upregulate under condition of II/R injury, and multiple miRNAs downregulate following II/R damage. Data of this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, Web of Science, and Scientific Information Database from 2000 to 2020. It is shown a correlation between changes in the expression of miRNAs and autophagy, inflammation, oxidative stress, apoptosis, and epithelial barrier function. Taken together, agomiR or antagomiR of some miRNAs can be considered as one new target for the research and development of innovative drugs to the prevention or treatment of II/R damage.

关键词： MicroRNAs Intestinal Ischemia/reperfusion injury

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Role of Zinc Supplementation on Ischemia/Reperfusion Injury in Various Organs

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BIOLOGICAL TRACE ELEMENT RESEARCH 2020年第1期196卷 1-9页

作者： akbari, ghaidafeh Yasuj Univ Med Sci Med Plants Res Ctr Yasuj Iran

Ischemia-reperfusion (I/R) injury is a serious condition which is associated with myocardial infarction, stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease, and sleep apnea and can lead to high morbidity and mortality. Salts of zinc (Zn) are commonly used by humans and have protective effects against gastric, renal, hepatic, muscle, myocardial, or neuronal ischemic injury. The present review evaluates molecular mechanisms underlying the protective effects of Zn supplement against I/R injury. Data of this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, and Scientific Information Database from 1991 to 2019. Zn supplementation increased the decreased parameters including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH), metallothionein (MT), protein sulfhydryl (P-SH), and nuclear factor-erythroid 2-related factor-2 (Nrf2) expression and decreased the increased elements such as endoplasmic reticulum (ER) stress, mitochondrial permeability transition pore (mPTP) opening, malondialdehyde (MDA), serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and microRNAs-(122 and 34a), apoptotic factors, and histopathological changes. Zn also increases phosphatidylinositol 3-kinase (PI3K)/Akt and glycogen synthase kinase-3 beta (GSK-3 beta) phosphorylation and preserves protein kinase C isoforms. It is suggested that Zn can be administered before elective surgeries for prevention of side effects of I/R injury.

关键词： Zinc supplementation Ischemia reperfusion injury Various organs

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A comprehensive review on regulatory effects of crocin on ischemia/reperfusion injury in multiple organs

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BIOMEDICINE & PHARMACOTHERAPY 2018年 99卷 664-670页

作者： akbari, ghaidafeh Mard, Seyyed ali Veisi, Ali Yasuj Univ Med Sci Yasuj Iran Ahvaz Jundishapur Univ Med Sci Sch Med Dept PhysiolPRC Res Ctr Infect Dis Digest SystAlimentary Tract R Ahvaz Iran Behbahan Fac Med Sci Behbahan Iran

Ischemia-reperfusion (I/R) injury affects o(2)-dependent organs including liver, kidneys, heart, brain, and intestine. I/R injury is described as the cellular injury in an organ caused by ischemia and then further aggravated during the reperfusion due to intracellular alterations. It is a process that happens in clinical settings such as organ transplantation, reperfusion after thrombolytic therapy, and coronary angioplasty. Crocus sativus L. known as saffron used in folk medicine for its beneficial effects. It contains multiple bioactive compounds including the crocin, crocetin, picrocrocin, and safranal. Crocin, a water-soluble carotenoid has antitumor, radical scavenging, anti hyperlipidemia and memory improving effects. Moreover, crocin has antioxidant, and protective effects on I/R models in rats at various organs such as heart, brain, kidney, stomach, liver, and kidney as described in detail in this review.

关键词： Ischemia/reperfusion injury Crocin Review Multiple organs

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The Effect of Zinc Sulfate on miR-122, miR-34a, Atioxidants, Biochemical and Histopathological Parameters Following Hepatic Ischemia/Reperfusion Injury in Rats

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BIOLOGICAL TRACE ELEMENT RESEARCH 2019年第2期188卷 434-440页

作者： Mard, Seyyed Ali akbari, ghaidafeh Dianat, Mahin Mansouri, Esrafil Ahvaz Jundishapur Univ Med Sci Sch Med Res Ctr Infect Dis Digest Syst PRCDept Physiol Ahvaz Iran Yasuj Univ Med Sci Med Sci Yasuj Iran Ahvaz Jundishapur Univ Med Sci Dept Physiol Sch Med PRC Ahvaz Iran Ahvaz Jundishapur Univ Med Sci Sch Med Cellular & Mol Res Ctr Dept Anat Sci Ahvaz Iran

Liver ischemia-reperfusion (IR) injury is a situation which occurs in various conditions such as pringle maneuver and liver transplantation. The regulatory effect of zinc sulfate (ZnSO4) is an important trace element on several liver disorders well known, but its effects on microRNA(S) (miR-122 and miR-34a) have not been evaluated. The goal of this study was to identify the protective effects of ZnSO4 on IR-induced liver injury, in particular, microRNA(S) in rats. Thirty-two male Wistar rats were randomly assigned into four groups (eight each group): sham, IR, ZnSO4 pretreatment, and ZnSO4 + IR groups. In sham and ZnSO4 pretreatment groups, animals received normal saline (N/S, 2ml/kg) and ZnSO4 (5mg/kg) for 7 consecutive days intraperitoneally (ip), then only laparotomy was performed. In IR and ZnSO4 + IR groups, N/S and ZnSO4, respectively, were given with the same dose, time, and route, before induction of ischemia for 45min followed by reperfusion for 60min. Blood sample was taken for biochemical and microRNAs analysis. Tissue specimens also were obtained for the measurements of antioxidant activities and histopathological evaluations. Our results showed that ZnSO4 pretreatment ameliorated histopathological changes decreased the increased serum levels of liver enzymes, miR-122 and miR-34a, and enhanced the decreased activity of antioxidant enzymes following hepatic IR injury. The present study indicated that ZnSO4 had potential hepatoprotective action against IR-induced injury. Therefore, it has been suggested that it can be administered as an anti-miR before elective hepatic surgeries for prevention of this complication.

关键词： Zinc sulfate Ischemia reperfusion Liver miR-122 miR-34a Rat

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Protective effects of crocin and zinc sulfate on hepatic ischemia-reperfusion injury in rats: a comparative experimental model study

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BIOMEDICINE & PHARMACOTHERAPY 2017年 96卷 48-55页

作者： Mard, Seyyed Ali akbari, ghaidafeh Dianat, Mahin Mansouri, Esrafil Ahvaz Jundishapur Univ Med Sci Res Ctr Infect Dis Digest Syst PRC Dept PhysiolSch Med Ahvaz Iran Ahvaz Jundishapur Univ Med Sci Sch Med Dept Physiol PRC Ahvaz Iran Ahvaz Jundishapur Univ Med Sci Sch Med Dept Anat Sci Cellular & Mol Res Ctr Ahvaz Iran

Objectives: The aim of this study was to investigate the comparative protective effects of separate and combined pretreatment with Cr and ZnSO4 on serum levels of miR-122, miR-34a, liver function tests, protein expression of Nrf2 and p53, and histopathological changes following IR-induced hepatic injury. Materials and methods: Fifty-six male Wistar rats randomly assigned into seven groups (n = 8). Sham (S), IR, crocin pretreatment (Cr), and crocin pretreatment + IR (Cr + IR), ZnSO4 pretreatment (ZnSO4), ZnSO4 pre-treatment + IR (ZnSO4 + IR) and their combination (Cr + ZnSO4 + IR) groups. In sham, ZnSO4 and Cr groups, animals received normal saline (N/S, 2 ml/day), Cr (200 mg/kg) and ZnSO4 (5 mg/kg) for 7 consecutive days (intraperitoneally;i.p), then only laparotomy was performed. In IR, Cr + IR, ZnSO4 + IR and Cr + ZnSO4 + IR groups, rats received N/S, Cr and ZnSO4 with same dose and time, then underwent a partial (70%) ischemia for 45 min that followed by reperfusion for 60 min. Blood sample was taken for biochemical and microRNAs assay, tissue specimens were obtained for antioxidants, protein expression, histopathological and immunohistochemical evaluations. Results: The results showed that Cr and ZnSO4 increased antioxidants activity and expression of Nrf2, decreased serum levels of liver enzymes, miR-122, miR-34a, p53 expression and also ameliorated histopathological abnormality. However, their combination caused more improvement on IR-induced liver injury. Conclusion: This study demonstrated that Cr, ZnSO4 and their combination through increasing antioxidant activity and Nrf2 expression, decreasing the serum levels of liver enzymes, miR-122, 34a, p53 expression, and amelioration of histopathological changes, protected liver against IR-induced injury.

关键词： Crocin ZnSO4 Hepatic Liver Ischemia Reperfusion Injury miR-122 miR-34a Rat Nrf2 Comparative Antioxidant Immunohistochemical

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The Hepatoprotective and MicroRNAs Downregulatory Effects of Crocin Following Hepatic Ischemia-Reperfusion Injury in Rats

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OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2017年第20170101期2017卷 11-11页

作者： akbari, ghaidafeh Mard, Seyyed Ali Dianat, Mahin Mansouri, Esrafil Ahvaz Jundishapur Univ Med Sci PRC Dept Physiol Sch Med Ahvaz Iran Ahvaz Jundishapur Univ Med Sci PRC Res Ctr Infect Dis Digest Syst Dept PhysiolSch Med Ahvaz Iran Ahvaz Jundishapur Univ Med Sci Sch Med Dept Anat Sci Cellular & Mol Res Ctr Ahvaz Iran

Background. Liver ischemia-reperfusion (IR) injury is one of the chief etiologies of tissue damage during liver transplantation, hypovolemic shock, and so forth. This study aimed to evaluate hepatoprotective effect of crocin on IR injury and on microRNAs (miR-122 and miR-34a) expression. Materials and Methods. 32 rats were randomly divided into four groups: sham, IR, crocin pretreatment (Cr), and crocin pretreatment + IR (Cr + IR) groups. In sham and Cr groups, animals were given normal saline (N/S) and Cr (200mg/Kg) for 7 consecutive days, respectively, and laparotomy without inducing IR was done. In IR and Cr + IR groups, N/S and Cr were given for 7 consecutive days and rats underwent a partial (70%) ischemia for 45 min/reperfusion for 60 min. Blood and tissue samples were taken for biochemical, molecular, and histopathological examinations. Results. The results showed decreased levels of antioxidants activity and increased levels of liver enzymes improved by crocin. The expression of miR-122, miR-34a, and p53 decreased, while Nrf2 increased by crocin. Crocin ameliorated histopathological changes. Conclusion. The results demonstrated that crocin protected the liver against IR injury through increasing the activity of antioxidant enzymes, improving serum levels of liver enzymes, downregulating miR-122, miR-34a, and p53, and upregulating Nrf2 expression.

关键词： Rats

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Renoprotective effects of zinc sulfate against transient liver ischemia/reperfusion injury in rats

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HELIYON 2023年第5期9卷 e15505页

作者： Gheitasi, Izadpanah Doustimotlagh, Amir Hossein Kokhdan, Esmaeel Panahi akbari, ghaidafeh Barmak, Mehrzad Jafari Yasuj Univ Med Sci Med Plants Res Ctr Yasuj Iran Yasuj Univ Med Sci Cellular & Mol Res Ctr Yasuj Iran Yasuj Univ Med Sci Med Physiol Yasuj Iran

Objectives: Liver ischemia/reperfusion damage frequently occurs in setting of hepatic resection and liver transplantation. It leads to disturbance in remote organs such as heart, lung and kidneys. This study explored the consequences of hepatic ischemia/reperfusion on the oxidative stress parameters, biochemical factors, and histopathological alterations in the kidney's rats, as well as evaluated the role of zinc sulfate on above-mentioned parameters. Materials and methods: Twenty-eight male Wistar rats were accidently assigned into four groups (n = 7). They were Sham, ischemia/reperfusion, zinc sulfate pretreatment, and zinc sulfate pretreatment + ischemia/reperfusion groups. Sham group: obtained normal saline (2 ml/day, seven consecutive days), intraperitoneally, zinc sulfate pretreatment group: obtained zinc sulfate (5 mg/kg, seven consecutive days, intraperitoneally). Ischemia/reperfusion group: obtained normal saline as mentioned previous, then rats experienced the partial ischemia (%70) for 45 min followed by 60 min reperfusion. Zinc sulfate pretreatment group: obtained zinc sulfate as mentioned previous, then rats experience the partial ischemia/reperfusion as presented earlier. At the end of investigation, blood was withdrawn, liver and renal tissues were removed. Then, biochemical and oxidative stress parameters, and histological changes were evaluated in the mentioned tissues. Results: The findings of this experiment indicated that zinc sulfate markedly reduced the serum levels of liver and kidney function tests in relative to ischemia/reperfusion group. Also, antiox-idant enzymes activity, ferric reducing antioxidant power, and nitric oxide significantly increased, while malondialdehyde level declined in the renal tissue of zinc sulfate + ischemia/ reperfusion group compared to ischemia/reperfusion rats. Furthermore, zinc sulfate alleviated the liver and kidneys histopathological alterations following ischemia/reperfusion. Conclusion: Zinc sulfate amelior

关键词： Liver Ischemia reperfusion Kidney Zinc sulfate Rat

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Molecular Mechanisms of Hawthorn Extracts in Multiple Organs Disorders in Underlying of Diabetes: A Review

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INTERNATIONAL JOURNAL OF ENDOCRINOLOGY 2022年第0期2022卷 2002768页

作者： Gheitasi, Izadpanah Savari, Feryal akbari, ghaidafeh Mohammadi, Jamshid Fallahzadeh, Ali Reza Sadeghi, Hossein Yasuj Univ Med Sci Med Plants Res Ctr Yasuj Iran Shoushtar Fac Med Sci Dept Basic Sci Shoushtar Iran Yasuj Univ Med Sci Cellular & Mol Res Ctr Yasuj Iran

Diabetes mellitus (DM) is one of the most important metabolic disorders associated with chronic hyperglycemia and occurs when the body cannot manage insulin secretion, insulin action, or both. Autoimmune destruction of pancreatic beta cells and insulin resistance are the major pathophysiological factors of types 1 and 2 of DM, respectively. Prolonged hyperglycemia leads to multiple organs dysfunctions, including nephropathy, neuropathy, cardiomyopathy, gastropathy, and micro- and macrovascular disorders. The basis of the metabolic abnormalities in carbohydrate, fat, and protein in diabetes is insufficient action of insulin on various target tissues. Medicinal plants are rich sources of bioactive chemical compounds with therapeutic effects. The beneficial effects of leaves, fruits, and flowers extracts of Crataegus oxyacantha, commonly called hawthorn, belonging to the Rosaceae family, are widely used as hawthorn-derived medicines. Data in this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, Web of Science, and Scientific Information Database from 2000 to 2021. Based on this review, hawthorn extracts appear both therapeutic and protective effects against diabetic-related complications in various organs through molecular mechanisms, such as decreasing triglyceride, cholesterol, very low density lipoprotein and increasing the antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity, decreasing malondialdehyde level, and attenuating tumor necrosis factor alpha, interleukin 6 and sirtuin 1/AMP-activated protein kinase (AMPK)/nuclear factor kappa B (NF-kappa B) pathway and increasing the phosphorylation of glucose transporter 4, insulin receptor substrate 1, AKT and phosphoinositide 3-kinases, and attenuating blood sugar and regulation of insulin secretion, insulin resistance, and improvement of histopathological changes in pancreatic beta cells. Collec

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