| Reference | [1]. Int J Exp Pathol. 2020 Dec;101(6):289-297. doi: 10.1111/iep.12376. Epub 2020 Oct 24.<br />
Tempol improves redox status in mdx dystrophic diaphragm muscle.<br />
Hermes TA(1), Mizobuti DS(1), da Rocha GL(1), da Silva HNM(1), Covatti C(1), Pereira ECL(1)(2), Ferretti R(3), Minatel E(1).<br />
Author information: (1)Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, Brazil. (2)Faculty of Ceilandia, University of Brasilia (UnB), Brasília, Brazil. (3)Department of Anatomy, Institute of Bioscience of Botucatu, São Paulo State University (UNESP), Botucatu, Brazil.<br />
Oxidative stress is a critical element in relationship to the pathophysiology of Duchenne muscular dystrophy (DMD). In the mice the diaphragm (DIA) is most resembles the dystrophic human pathology. In this study we have evaluated the consequences of a synthetic antioxidant (tempol) on oxidative stress parameters in the DIA muscle of mdx mice. The mdx mice were separated into two groups: mdx, the control group receiving intraperitoneal (i.p.) injections of saline solution (100 µL), and mdxT, the treated group receiving i.p. injections of tempol (100 mg/kg). The tempol-treated group showed reduced oxidative stress markers, decreasing the dihydroethidium reaction (DHE) area; autofluorescent lipofuscin granules; and 4-hydroxynonenal (4-HNE)-protein adduct levels. DIA muscle of mdx mice. At the same time, the manganese-superoxide dismutase 2 (SOD2) levels were increased in the tempol-treated group. In addition, the tempol-treated group showed reduced levels of glutathione-disulphide reductase (GSR), glutathione peroxidase 1 (GPx1) and catalase (CAT) in immunoblots. The tempol-treated group has also shown lower relative gene expression of SOD1, CAT and GPx than the non-treated group. Our data demonstrated that tempol treatment reduced oxidant parameters and increased anti-oxidant SOD2 levels in the DIA muscle of mdx mice, which may contribute to the normalization of the redox homeostasis of dystrophic muscles.<br />
DOI: 10.1111/iep.12376 PMCID: PMC7691217 PMID: 33098599 [Indexed for MEDLINE]<br />
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[2]. Hum Exp Toxicol. 2019 Jun;38(6):713-723. doi: 10.1177/0960327119836203. Epub 2019 Mar 29.<br />
Anti-inflammatory role of tempol (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) in nephroprotection.<br />
Afjal MA(1), Abdi SH(1), Sharma S(1), Ahmad S(1), Fatima M(1), Dabeer S(1), Akhter J(1), Raisuddin S(1).<br />
Author information: (1)Department of Medical Elementology and Toxicology, School of Chemical & Life Sciences, Jamia Hamdard (Hamdard University), New Delhi, India.<br />
Inflammation is one of the mechanisms involved in the acute kidney injury (AKI) caused by cisplatin (CP)-induced nephrotoxicity. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) has powerful antioxidant activity. We investigated its potential nephroprotective effects and the underlying mechanisms that may add further benefits to its clinical usefulness in a CP-induced AKI model. Male Swiss albino mice were divided randomly into four groups: control, CP (20 mg/kg intraperitoneally), tempol (100 mg/kg/day, per os) + CP, and tempol only treatments. Blood samples were collected to analyze renal function parameters. Immunoblotting and immunohistochemical analysis were used to assess the level and localization of inflammatory markers. Tempol afforded protection to animals from CP-induced elevation of inflammatory markers as indicated by reduced expression of nuclear factor-kappa B, cyclooxygenase-2, and tumor necrosis factor-α in kidney tissue. Histological findings and analysis of kidney function markers corroborated with these findings confirming a nephroprotective role for tempol. In conclusion, this study provides important evidence for the promising anti-inflammatory effects of tempol which appears to contribute significantly to its nephroprotective action.<br />
DOI: 10.1177/0960327119836203 PMID: 30924375 [Indexed for MEDLINE]<br />
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[3]. Nan Fang Yi Ke Da Xue Xue Bao. 2019 Aug 30;39(8):883-890. doi: 10.12122/j.issn.1673-4254.2019.08.02.<br />
[Effect of the chemoprotectant tempol on anti-tumor activity of cisplatin].<br />
[Article in Chinese]<br />
Ye S(1), Zeng S(1), Huang M(1), Chen J(1), Chen X(1), Xu P(1), Wang Q(1), Gao W(1), Yang B(2), Hao B(1), Huang W(3)(4), Liu Q(1)(5).<br />
Author information: (1)Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University/Guangdong Provincial Key Laboratory of Cancer Immunotherapy/Guangzhou Key Laboratory of Tumor Immunology Research, Guangzhou 510515, China. (2)Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China. (3)National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China. (4)Department of Human Anatomy, School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang 524003, China. (5)Center for Medical Transformation, Shunde Hospital, Southern Medical University, Foshan 528300, China.<br />
OBJECTIVE: To investigate the effect of the chemoprotectant tempol on the anti-tumor activity of cisplatin (DDP). METHODS: The cellular toxicity of tempol in human colon cancer SW480 cells and mouse colon cancer CT26 cells were evaluated using MTT and cell counting kit-8 assays. CalcuSyn software analysis was used to determine the interaction between tempol and DDP in inhibition of the cell viability. A subcutaneous homograft mouse model of colon cancer was established. The mice were randomly divided into control group, tempol group, cisplatin group and tempol + DDP treatment group with intraperitoneal injections of the indicated agents. The tumor size, body weight and lifespan of the mice were measured, and HE staining was used to analyze the cytotoxic effect of the agents on the kidney and liver. Immunohistochemistry and Western blotting were performed to detect the expression of Bax and Bcl2 in the tumor tissue, and TUNEL staining was used to analyze the tumor cell apoptosis. The level of reactive oxygen species (ROS) in the tumor tissue was determined using flow cytometry. RESULTS: Tempol showed inhibitory effects on the viability of SW480 and CT26 cells. CalcuSyn software analysis showed that tempol had a synergistic anti-tumor effect with DDP (CI < 1). In the homograft mouse model, tempol treatment alone did not produce obvious anti-tumor effect. HE staining showed that the combined use of tempol and DDP alleviated DDP-induced fibrogenesis in the kidneys, but tempol also reduced the anti-tumor activity of DDP. Compared with the mice treated with DDP alone, the mice treated with both tempol and DDP had a significantly larger tumor size (P < 0.01) and a shorter lifespan (P < 0.05). Tempol significantly reversed DDP-induced expression of Bax and Bcl2 in the tumor tissue and tumor cell apoptosis (P < 0.001), and obviously reduced the elevation of ROS level in the tumor tissue induced by DDP treatment (P < 0.05). CONCLUSIONS: Tempol can attenuate the anti-tumor effect of DDP while reducing the side effects of DDP. Caution must be taken and the risks and benefits should be carefully weighed when considering the use of tempol as an anti-oxidant to reduce the toxicities of DDP.<br />
DOI: 10.12122/j.issn.1673-4254.2019.08.02 PMCID: PMC6765593 PMID: 31511206 [Indexed for MEDLINE]<br />
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[4]. Eur J Pharmacol. 2020 Nov 5;886:173439. doi: 10.1016/j.ejphar.2020.173439. Epub 2020 Aug 29.<br />
Tempol prevents isoprenaline-induced takotsubo syndrome via the reactive oxygen species/mitochondrial/anti-apoptosis /p38 MAPK pathway.<br />
Qi C(1), Liu X(2), Xiong T(2), Wang D(3).<br />
Author information: (1)Department of Cardiology, The Third Affiliated Hospital of Nanjing Medical University; Sir Run Run Hospital Affiliated to Nanjing Medical University, 109#, Longmian Ave, Nanjing, Jiangsu, China. Electronic address: [email protected]. (2)Department of Cardiology, The Second Xiangya Hospital of Central South University, 172#, Tongzipo Ave, Changsha, HuNan, China. (3)Clinical Medical College Yangzhou University, 88(#) South University Ave, Yangzhou; Jiangsu, China; Department of Medical Research Centre, Northern Jiangsu People's Hospital, 98#,West Nantong Ave, Yangzhou, Jiangsu, Zip code, 225009, China. Electronic address: [email protected].<br />
Takotsubo Syndrome (TS) is a kind of acute cardiac syndrome with a complex pathophysiological mechanism that remains to be elucidated. The relationship between TS and reactive oxygen species has received increasing attention over in recent years. Therefore, the relationship between TS and reactive oxygen species was investigated in vivo and in vitro. Isoprenaline (ISO) was used to induce TS and tempol (quercetin) was selected as a scavenger to eliminate reactive oxygen species in animal experiments, and echocardiography was used to determine the incidence of TS. The H9C2 cells were cultured with different reagents to investigate the detailed mechanism; Reactive oxygen species levels and mitochondrial function were evaluated. Cell apoptosis rate was analyzed by TUNEL staining and the proteins involved in the signaling pathways were examined by Western blotting. It was found that a high dose of tempol almost eliminated TS and protected the cardiac function. Moreover, tempol also decreased the reactive oxygen species levels and reduced lipid droplet deposition in myocardial tissue. In terms of the cultured cells, tempol preconditioning decreased reactive oxygen species production as well as lipid droplet deposition, and protected the mitochondrial function by reducing mitochondrial swelling, thereby maintaining the mitochondrial membrane potential (ΔΨm) at a level that was higher than that of controls. Furthermore, tempol could reduce cells apoptosis after ISO treatment and decrease the protein level of p38, which is a member of the MAPK family, which and thus plays an important role in regulating cells apoptosis. This antiapoptotic effect of tempol was similar to that of a control reagent, SB203580, which is a specific inhibitor of phospha-p38 (p-p38). This study demonstrated, for the first time, a sudden increase in reactive oxygen species and effects of the downstream cascades play core roles in the development of TS.<br />
DOI: 10.1016/j.ejphar.2020.173439 PMID: 32871175 [Indexed for MEDLINE]<br />
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[5]. Life Sci. 2019 Mar 15;221:65-71. doi: 10.1016/j.lfs.2019.02.016. Epub 2019 Feb 7.<br />
Tempol improves oxidant/antioxidant parameters in testicular tissues of diabetic rats.<br />
Shateri H(1), Ranjbar A(2), Kheiripour N(3), Ghasemi H(4), Pourfarjam Y(5), Habibitabar E(1), Gholami H(1), Moridi H(6).<br />
Author information: (1)Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. (2)Department of Toxicology and Pharmacology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran. (3)Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan. Iran. (4)Department of Clinical Biochemistry, Abadan School of Medical Sciences, Abadan, Iran. (5)Department of Chemistry, University of Cincinnati, Cincinnati, OH, United States of America. (6)Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address: [email protected].<br />
AIMS: Oxidative stress induced by diabetes mellitus (DM) is considered as one of the main causes of infertility in diabetic patients. The aim of the present study was to assess the effect of Tempol – as a synthetic antioxidant- on the testis oxidative stress and sperm parameters in type 2 diabetic (T2D) rats. MAIN METHODS: Twenty male Wistar rats were divided into 4 groups. Control groups (C) and diabetic groups (D); the control and diabetic groups received Tempol (100 mg/kg) for one month. Sperm parameters and oxidative stress biomarkers were evaluated in testicular tissue. KEY FINDINGS: The results demonstrated that administration of Tempol in diabetic rats improved sperm motility and viability and decreased the count of abnormal sperms. Also Tempol decreased the fasting blood sugar (FBS) and lipid peroxidation (LPO). In addition, Tempol significantly increased total antioxidant capacity (TAC) levels in testis tissue of T2D rats. Histopathological changes were also improved in the diabetic treated group. SIGNIFICANCE: Taken together, the results indicated that Tempol improved fertility parameters in a diabetic rat through reducing oxidative stress.<br />
DOI: 10.1016/j.lfs.2019.02.016 PMID: 30738867 [Indexed for MEDLINE]
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