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Roles of Simvastatin and Sildenafil in Modulation of Cranial Irradiation-Induced Bystander Multiple Organs Injury in Rats.
- Source :
-
Inflammation [Inflammation] 2021 Dec; Vol. 44 (6), pp. 2554-2579. Date of Electronic Publication: 2021 Aug 21. - Publication Year :
- 2021
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Abstract
- In radiobiology and radiation oncology fields, the observation of a phenomenon called radiation-induced bystander effect (RIBE) has introduced the prospect of remotely located tissues' affection. This phenomenon has been broadly developed to involve the concept of RIBE, which are relevant to the radiation-induced response of a distant tissue other than the irradiated one. The current study aimed at investigating each of the RIBE of cranial irradiation on oxidative and inflammatory status in different organs such as liver, kidney, heart, lung, and spleen. Being a vital target of the cholinergic anti-inflammatory response to an inflammatory stimulus, the splenic α-7-nicotinic acetylcholine receptor (α-7nAchR) was evaluated and the hepatic contents of thioredoxin, peroxisome proliferator-activated receptor-alpha and paraoxinase-1 (Trx/PPAR-α/PON) were also assessed as indicators for the liver oxidative stress and inflammatory responses. Being reported to act as antioxidant and anti-inflammatory agents, simvastatin (SV) and/or sildenafil (SD) were investigated for their effects against RIBE on these organs. These objectives were achieved via the biochemical assessments and the histopathological tissues examinations. Five experimental groups, one sham irradiated and four irradiated groups, were exposed to cranial irradiation at dose level of 25 Gy using an experimental irradiator with a Cobalt (Co <superscript>60</superscript> ) source, RIBE, RIBE + SV (20 mg.(kg.bw) <superscript>-1</superscript>  day <superscript>-1</superscript> ), RIBE + SD (75 mg.(kg.bw) <superscript>-1</superscript>  day <superscript>-1</superscript> ), and RIBE + SV + SD. Cranial irradiation induced structural, biochemical, and functional dys-regulations in non-targeted organs. RIBE-induced organs' injuries have been significantly corrected by the administration of SV and/or SD. Our results suggest the possibility of a potentiated interaction between SV and SD in the modulation of the RIBE associated with head and neck radiotherapy.<br /> (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Animals
Aryldialkylphosphatase metabolism
Bystander Effect radiation effects
Heart drug effects
Heart radiation effects
Inflammation Mediators metabolism
Kidney drug effects
Kidney metabolism
Kidney radiation effects
Liver drug effects
Liver metabolism
Liver radiation effects
Lung drug effects
Lung metabolism
Lung radiation effects
Male
Oxidative Stress
PPAR alpha metabolism
Radiation Dosage
Rats, Wistar
Spleen drug effects
Spleen metabolism
Spleen radiation effects
Thioredoxins metabolism
alpha7 Nicotinic Acetylcholine Receptor metabolism
Rats
Anti-Inflammatory Agents pharmacology
Antioxidants pharmacology
Bystander Effect drug effects
Cranial Irradiation adverse effects
Organs at Risk radiation effects
Sildenafil Citrate pharmacology
Simvastatin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2576
- Volume :
- 44
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Inflammation
- Publication Type :
- Academic Journal
- Accession number :
- 34420155
- Full Text :
- https://doi.org/10.1007/s10753-021-01524-w