Mitigation of Radiation-induced Pneumonitis and Lung Fibrosis using Alpha-lipoic Acid and Resveratrol

Abstract

Background: Lung is a radiosensitive organ. Studies have shown that exposure of the lung to acute and high doses of radiation following inhalation of radioactive agents or an accidental radiological event may lead to pneumonitis and fibrosis, which are associated with a risk of death. So far, some agents have been studied for mitigation of pneumonitis and fibrosis following exposure of murine lung tissues to ionizing radiation. In this study, we aimed to detect the possible mitigatory effect of alpha-lipoic acid, resveratrol and their combination on mice pneumonitis and fibrosis markers following irradiation. Methods: 25 mice were divided into 5 groups: control, radiation; radiation plus alpha-lipoic acid; radiation plus resveratrol; and radiation plus both resveratrol and alpha-lipoic acid. Mice chest regions were irradiated with 18 Gy using a cobalt-60 gamma rays source. Treatments started 24 h after irradiation and continued for two weeks. After 100 days, all mice were sacrificed and their lung tissues removed for histopathological evaluation. Results: Pathological study showed that exposure to radiation led to severe pneumonitis and moderate fibrosis after 100 days. Both resveratrol and alpha-lipoic acid, as well as their combination could mitigate pneumonitis and fibrosis markers. Although, resveratrol could not mitigate infiltration of most inflammatory cells as well as inflammation and vascular damage, alpha-lipoic acid and its combination were able to mitigate most damaged markers. Conclusion: Alpha-lipoic acid and its combination with resveratrol were able to mitigate fibrosis and pneumonitis markers in mice lung tissues following lung irradiation. Although resveratrol has a protective effect on some markers, it has a weaker effect on lung injury. In conclusion, our results suggest that the combination of resveratrol and alpha-lipoic acid has a potent mitigatory effect compared to the single forms of these agents.

Modulation of COX-2 and NADPH oxidase-4 by Alpha-lipoic acid ameliorates busulfan-induced pulmonary injury in rats.

“…This was supported by the nding conducted by Azmoonfar et.al. (Azmoonfar et al 2019) who reported that ALA was able to mitigate brosis and pneumonitis markers in mice lung tissues following lung irradiation.…”

Mitigation of Radiation-Induced Lung Pneumonitis and Fibrosis Using Metformin and Melatonin: A Histopathological Study

“…The microscope’s field of view was 22 for ocular lens and 5.512 for objective lens. Thereafter, results were reported and scored according to our previous study [17].…”

Potential roles of mitochondrial cofactors in the adjuvant mitigation of proinflammatory acute infections, as in the case of sepsis and COVID-19 pneumonia

“…A number of studies in the recent decade have tested the ALA-associated anti-inflammatory effects on rats [78][79][80][81][82][83][84][85][86] and mice [87,88]. The model disorders included multiple-organ sepsis [78,81,82,86], endotoxemia [79], metal or organic poisoning [81,84], and radiation-induced damage [88]. Altogether, ALA administration was found to decrease inflammatory response, H 2 O 2 , MDA levels, myeloperoxidase activity, and cytokine levels.…”

“…Of patients Duration Effects References ALA Hemodialysis 63 8 weeks Decreased C-reactive protein (CRP) [ 83 ] Cardiopulmonary surgery 30 24 ± 9.4 months Significantly decreased IL-6 and IL-8 levels [ 84 ] Ischemia–reperfusion injury 26 > 14 days Decreased inflammatory markers, and early kidney dysfunction and pancreatitis [ 85 ] CoQ10 Septic shock 14 72 h Significantly lower CoQ10 plasma levels in septic shock patients than in healthy controls. CoQ10 negatively associated with inflammatory molecules [ 86 ] Acute influenza 50 3 influenza seasons Significantly lower CoQ10 plasma levels in patients with acute influenza infection [ 87 ] Papillomavirus skin warts 156 90 days Decreased viral load and increased antiviral cytokine levels [ 88 ] CARN Hemodialysis or chronic peritoneal dialysis 113 6 months Suppressed inflammation, CRP [ 89 ] Hemodialysis 42 6 months Decreased CRP [ 90 ] Hemodialysis …”