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and the total micronuclei values 1 hour after finishing oral supplementation were decreased by more than 40 % comparing with similarly irradiated whole blood collected at the beginning , specifically in the combined treatment group , the total micronuclei values were reduced by 50 % ( Rostami et al ., 2016 ).
Beyond the involvement of selenium in the process of spermatogenesis , previous studies have proven that it can also improve sperm motility and semen quality ( Moslemi and Zargar , 2011 ). Given its vulnerability to environmental toxic agents , even regular therapeutic dose of radiotherapy ( RT ) may have detrimental impact on spermatogenesis system . Bagheri et al . conducted their experiments by feeding mice selenium and zinc before radiation and evaluated the radioprotective effect through histopathological results . The findings revealed that both selenium and zinc supplementation before radiation could reverse the reduction of spermatogonia . Notably , apart from the edema , selenium could reverse the damage caused by 2Gyofg irradiation including spermatogenic arrest , atrophy of seminiferous tubules , thickening of basal lamina , leydig cell hyperplasia , epididymis decreased sperm density and epididymis vacuolatio , meanwhile selenium showed no toxicity to spermatogenesis in comparison with the mice without radiation treatment . During the assessment of histopathological results , zinc not only exhibited less radioactive protective effect for its protective ability merely to basal lamina and epididymis but also caused damage to seminiferous tubules . And strikingly , zinc treatment without radiation induced damage in epididymis ( Bagheri et al ., 2019 ).
3 Selenomethioine
Selenomethionine [ C 5 H 11 NO 2 Se ] ( Se-Met ) is deemed to be an appropriate supplemental form of selenium for its outstanding bioavailability and low toxicity in comparison to other selenium compounds ( Wang et al ., 2007 ). With the presence of both selenium and methionine , Seleno-L-Methionine ( Se-L-Met ) is the L-isomer of Se-Met and both of which could act as potent antioxidants and scavenge ROS .
A study designed by Fisher et al . explored the protective effects of selenium against DNA damages , revealing that the selenium supplementation in the form of Se-L-Met at a relatively physiological and nontoxic concentration could increase the levels of p53 and redox factor-1 ( Ref-1 ) proteins , meanwhile p53 cysteine residues 275 and / or 277 were reduced , being consilient with former studies ( Pluquet and Hainaut , 2001 ). P53 cysteine residues 275 and / or 277 are specifically crucial for the binding of p53 and downstream effector gene sequences , meanwhile Ref-1 was essential for selenium signal transduction to p53 ( Seo et al ., 2002 ). Breast cancer susceptibility gene 1 ( Brca1 ) is a tumor suppressor gene being involved in the repair of DNA damage ( Jasin , 2002 ). Se-L-Met may effectively influence related processes . Their further study suggested that the protective effect of Se-L-Met did not extend to Brca1-deficient fibroblasts from UV-radiation , indicating that in addition to p53 and Ref-1 , Brca1 may also be considered to take an important place in the DNA protection enhanced by Se-L-Met ( Fischer et al ., 2006 ).
Previous studies have reported that Se-Met could efficiently inhibit the formation of lipid peroxy radicals , preventing lipid peroxidation ( Dowlath et al ., 2021 ). Guo et al . had demonstrated in their research that Se-Met , composing over 90 % of selenium content , acts as the primary form of selenium in Se-rich yeast peptide fractions . By scavenging the free radical and inhibiting the lipid peroxidation , Se-rich peptide fraction together with yeast extract enzyme ( abbreviated as sSeP ) presents its remarkable synergistic antioxidant in vitro . Experiments in vivo also manifested its significant antioxidant activity through abating malonaldehyde ( MDA ) as well as increasing GPx , had shown significant antioxidant activity in vivo . Furthermore , the application of sSeP on shaved dorsal skin of UVB-irridated mice could significantly alleviated morphological changes ( including drier skin , redness , edema formation and increased scaly wrinkle ) as well as histopathological changes ( mainly epidermis thickness ). Additionally , sSeP was testified to enhance the expression of aquaporin-3 and attenuate the phosphorylation of p38 MAPK in H 2 O 2- treated HaCaT cells ( a human epidermal keratinocytes cell line ), providing a potential mechanism for sSeP to alleviate UVB-induced oxidative damages in skin of mice ( Guo et al ., 2020 ).
Brown et al . demonstrated that antioxidant food supplementation including Se-L-Met could scavenge ROS after totalbody irradiation ( TBI ), and improve DNA damage and apoptosis in bone marrow cells ( Brown et al ., 2010 ). Bagheri et al . assessed chromosome damage through the micronuclei test , revealing that comparing to the control group , 2 Gy irradiated rats manifest a significant increase in micronucleus frequency , which could be markedly decreased by preadministration with Se-L-Met . And in contrast with the control group , the impact of ionizing radiation ( IR ) to cell proliferation could be significantly suppressed with the preconditioning of Se-L-Met . Curcumin [ 1,7-bis ( 4-hydroxy-3-methoxyphenyl ) - 1,6-heptadiene-3,5dione ], a natural pigment with broad economic value and pharmacological effects , is widely known for its anti-inflammatory and antioxidant potential , and is also considered to be protective from DNA damage caused by radiation ( Srinivasan et al ., 2006 ). By controlling the variables , Bagheri et al . also confirmed that the combined form of Se-L-Met and curcumin outperformed the effects of Se-L-Met or curcumin alone ( Bagheri et al ., 2017 ).
Usually , RT will not result in severe damages to lung immediately but further influences including pneumonitis and fibrosis may contribute to the limited dose of RT for malignant tumors of organs in the chest area . These two pathological changes are related to the changes of inflammatory factors and cytokines caused by chronic oxidative stress . Previous studies proved that IL-4 plays an instrumental role in late effects of radiation-induced lung injuries as potent pro-fibrotic cytokines , and mainly causes the constant production of ROS after IR . Being related to the oxidation process in the body and involved in the inflammatory response , dual oxidase 1 ( Duox1 ) and dual oxidase 2 ( Duox2 ) are nicotinamide adenine dinucleotide phosphate ( NADPH ) oxidases . IL-4 could upregulate interleukin-4 receptor subunit alpha-1 ( IL4Ra1 ), thus stimulating Duox1 and Duox2 and ultimately mediate the continuous production of H 2 O 2 ( Raad , 2013 ). Ameziane et al . had demonstrated that the upregulation of IL-4 after irradiation could induce the expression of dual oxidases including Duox1 and Duox2 , thus leading to the chronic production of ROS and instability of genome ( Ameziane-El-Hassani et al ., 2015 ).