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Normal Tissue Tolerance
Published in Loredana G. Marcu, Iuliana Toma-Dasu, Alexandru Dasu, Claes Mercke, Radiotherapy and Clinical Radiobiology of Head and Neck Cancer, 2018
Loredana G. Marcu, Iuliana Toma-Dasu, Alexandru Dasu, Claes Mercke
Nitroxide compounds have been investigated as possible radioprotectors over the last couple of decades, due to their ability to alter the tissue’s redox status and to modify oxidative stress (Soule 2007). It was shown that both nitroxides radical and hydroxylamines (the reduction products), are recycling antioxidants that protect the cell against the oxidative stress, including the highly damaging hydrogen peroxide (Soule et al. 2007). The most representative nitroxide compound to date is tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), which has been investigated in preclinical settings. In vivo animal studies showed that tempol was effectively protecting the salivary glands, without influencing tumour control (Cotrim et al. 2007), thus demonstrating a differential protection of normal tissues as compared to tumour cells.
Radiotherapy-induced severe oral mucositis: pharmacotherapies in recent and current clinical trials
Published in Expert Opinion on Investigational Drugs, 2023
Alessandro Villa, Stephen T. Sonis
Radioprotective activities for Tempol were first described in 1991 [36]. Nitroxides are a group of low molecular weight compounds that function as superoxide dismutase mimics to reduce oxidative stress. Other activities ascribed to Tempol include inhibition of NF-κB, proinflammatory cytokine levels and transforming growth factor beta (TGF-β)/mothers against decapentaplegic homolog 3 (SMAD-3)-induced fibrosis [37]. Tempol has been studied as a potential intervention for a range of radiation-associated toxicities including xerostomia [38,39]. Data from preclinical studies in mice and minipigs, in which animals were challenged with fractionated doses of radiation, suggested that topical and injected formulations of Tempol favorably impacted the course of radiation-induced OM [40,41].
Tempol (4-hydroxy tempo) protects mice from cisplatin-induced acute kidney injury via modulation of expression of aquaporins and kidney injury molecule-1
Published in Drug and Chemical Toxicology, 2022
Mohd Amir Afjal, Poonam Goswami, Shahzad Ahmad, Sadaf Dabeer, Juheb Akhter, Mohd Salman, Anuradha Mangla, Sheikh Raisuddin
Tempol is a pharmaceutical compound of interest. It is a membrane-permeable radical scavenger with SOD mimetic activity and other antioxidant activities such as anti-lipid peroxidation (LPO) (Ahmed et al. 2014, Youn et al. 2016). Most of the antioxidants have membrane stabilizing effect, as they prevent LPO as the first order of defense. LPO has cascading effect not only on cell membrane but also on cellular functions and intracellular homeostatis. Antioxidants also augment cell membrane integrity. AQPs are membrane proteins and therefore an antioxidant by way of its protective effect on cell membrane/LPO is likely to protect AQPs. AVP is reported to regulate AQP (He and Yang 2019). It has been shown that tempol prevents renal proximal tubular cell apoptosis, and inhibits mitochondrial dysfunction, DNA damage and inflammation (Ahmed et al. 2014, Youn et al. 2016, Soni et al. 2018, Afjal et al. 2019). In this study, we explored effect of tempol on AQP and AVP expression in case of CP-induced AKI in mice. Tempol pretreatment showed a significant restoration in mRNA expression of AQP1, AQP2, AQP3, AQP4, AVP and KIM-1 in mice which also helped in AQP accumulation at the apical membrane of mouse kidney. This may be one of the factors which might have resulted in protection afforded by tempol to AVP/AQPs. However, more confirmatory studies are required to conclusively prove this relationship.
Tempol modulates the leukocyte response to inflammatory stimuli and attenuates endotoxin-induced sickness behaviour in mice
Published in Archives of Physiology and Biochemistry, 2020
Samuel Nuno Pereira Lima, Cláudio Daniel Cerdeira, Gérsika Bitencourt Santos, Mateus de Mello Fernandes, Alexandre Giusti-Paiva, Maísa Ribeiro Pereira Lima Brigagão
In the present study, we tested the effects of Tempol on multiple key effectors and outcomes of inflammation. The positive effects of this nitroxide in an experimental mouse model were demonstrated. The discovery and development of new compounds with anti-inflammatory activity, has received a new impetus due to an increase in both population life expectancy and inflammatory disease incidence, which was followed by questions related to the safety of current anti-inflammatory drugs (Bidaut-Russell and Gabriel 2001, Vardeny and Solomon 2008). Traditionally, cyclooxygenase inhibitors are the most studied compounds able to act on a specific metabolic pathway active during inflammation, but this does not exclude the likelihood that new cellular targets, such as ROS production and other cellular signalling pathways, could be used for this purpose (Mitchell et al. 1991, Simmons 2006).