The effects of N-acetylcysteine on radiotherapy-induced small intestinal damage in rats

Abstract

Six million cancer patients worldwide receive radiotherapy, either alone or in combination with other cancer treatments annually. The purpose of this study was to investigate, at the structural and molecular levels, the protective effect of N-acetylcysteine (NAC), a powerful antioxidant, against radiotherapy-induced damage on the intestinal system. Three study groups were constituted: control (group 1: no radiotherapy), radiotherapy (RT; group 2), and RT + NAC (group 3). The NAC group received 300 mg/kg NAC orally for five days before irradiation. At the end of the 5th day, 6 Gy was irradiated once, and 300 mg/kg NAC was administered orally for two days following irradiation. NAC drug administration was maintained for a total of seven days. At the end of the study, the rats were euthanized by the administration of anesthetic agents and sacrificed. The malondialdehyde (MDA) levels and caspase-3 expression increased and glutathione (GSH) levels decreased in RT rats compared to the control group ( p < 0.05). NAC reduced MDA levels, and caspase-3 expression, and increased GSH levels in the small intestine caused by RT ( p < 0.05). Therefore, NAC may be useful in the prevention of gastrointestinal syndrome in patients undergoing radiotherapy in the treatment of malignancy. Impact statement Some six million cancer patients currently receive radiotherapy. Radiotherapy eliminates cancer cells by accelerating their death. However, radiotherapy is not selective, and it therefore harms healthy tissues around cancerous tissue. The latest studies have shown that the irradiation of biological materials causes a rapid increase in reactive oxygen species (ROS) in the tissue as a result of exposure of the target molecule to direct and indirect ionization. N-acetylcysteine (NAC) is an antioxidant that permits the elimination of free oxygen radicals and that contributes to glutathione synthesis. Our study, therefore, examined the effects of radiation resulting from radiotherapy on the small intestine at the molecular level, and prospectively considered the potential protective characteristics of NAC against gastrointestinal syndrome resulting from radiotherapy.

Disturbances in Thyroid Hormone Metabolism in Rats Exposed to γ- Radiation and Carbon Tetrachloride: The Role of N- acetyl cysteine and Sodium Selenite

“…The histopathological examination of liver tissue supported the biochemical results and confirmed the ameliorative effect NAC and Se against ionizing radiation and / or CCl 4 . These results are in agreement with the findings of Mercantepe et al (2019) who observed that NAC manifested protective effect at the structural and molecular levels against gastrointestinal syndrome resulting from radiotherapy. Additionally, Se supplementation improved liver histopathological criteria against bisphenol Ainduced hepatotocixity in rats (Abdel Samie et al, 2017).…”

“…The results suggest that NAC and sodium selenite have the ability to increase the antioxidant capacity, quench free radicals and prevent cellular membranes from being damaged by free radicals. These results come in accordance with those of Mercantepe et al (2019) who reported that NAC exhibited protective effects in rats against radiation-induced intestinal damage. Pei et al (2018) demonstrated that NAC directly interacts with the free radicals via its thiol side -chain.…”

“…As well known, antioxidant therapy has the potential to attenuate the injury induced by exposure to oxidative stress. NAC, which is a precursor of cysteine and glutathione, can suppress ROS production (Mercantepe et al, 2019). Also, sodium selenite, which can regulate the cellular antioxidant capacity (Amuru et al, 2019), has an important role in the metabolism of thyroid NAHED ABDEL-AZIZ hormones, where it is considered as an integral part of deiodinase enzymes responsible for activation and inactivation of thyroid hormones (Sobolev et al, 2018).…”

“…Therefore, a great deal of effort is being conducted to search for free radical scavenging agents that can counteract excess ROS and improve endogenous antioxidant system. Glutathione elevating agents, such as Taurine, alpha-lipoic acid and N-acetyl cysteine (NAC), are non-toxic (at certain levels), and were reported to protect tissues against radiation damage (El-Maraghi et al, 2018;Kim et al, 2019;Mercantepe et al, 2019). Recently, Abrigo et al (2020) reported that NAC treatment inhibited all the mechanisms associated with myonuclear apoptosis in chronic liver disease induced muscle atrophy.…”

Dose- and Segment-Dependent Disturbance of Rat Gut by Ionizing Radiation: Impact of Tight Junction Proteins

“…Moreover, an increased caspase-3 activation signal, suggesting apoptosis stimulation in intestinal crypts, is also involved in GIARS pathology [ 9 ]. The manifestation of GIARS in mammals is associated with weight loss, decreased nutrient absorption, profuse diarrhea and progressive dehydration, as well as bacterial translocation into the bloodstream [ 2 , 10 ].…”