292 J . Yan and D . Li : Radioprotection 2024 , 59 ( 4 ), 287 – 295
5 Sodium selenite
Sodium selenite [ Na 2 SeO 3 ] has long been recognized as one of the most redox-active selenium compounds and exhibiting potent anticancer properties , and notably , sodium selenite is considered to generate ROS which is contrary to the consensus that selenium is an antioxidant . Its high biological activity is attributed to its ability to primarily enhance the expression of selenoproteins , thus sodium selenite may not be inherently antioxidant until incorporated into selenoproteins with oxidoreductase functions ( Misra et al ., 2015 ; Spallholz , 1994 ).
Iodine-131 ( 131 I ) is an effective treatment against thyroid cancer which is considered as one of the most common tumors of the endocrine system . Beyond the intake of the thyroid tissue , salivary glands could also accumulate radioiodine through the sodium iodide symporter ( NIS ). Due to the high proportion of radio-sensitive serous acinar cells , parotid glands are especially vulnerable to radiation ( Choi et al ., 2013 ; De La Vieja et al ., 2000 ). Individuals undergoing high-dose treatment of 131 I may suffer temporary or permanent dysfunction of salivary glands accompanied by symptomatic sialadenitis , thus leading to severe impact to quality of life ( An et al ., 2013 ). Selenium has been demonstrated to be radioprotective on parotid glands against g radiation and on the blood cells against 131 I radiation in animal studies ( Tuji et al ., 2010 ). Son et al .
performed a prospective study that contains 2 groups of thyroid cancer patients post-total thyroidectomy , 8 patients were divided in each group for 131 I treatment . Both serum amylase level and salivary gland scintigraphy manifested the protective effect of sodium selenite against salivary glands after 131 I therapy ( Son et al ., 2017 .).
Puspitasari et al . proved that the sodium selenite could increase GPx-1 activity in a dose- and time-dependent manner . The administration of a 50nM sodium selenite solution to checkpoint kinase 1 ( CHECK-1 ) non-cancerous human esophageal cells for 72 h could induce the highest activity of GPx-1 . With the supplementation of 50 nM sodium selenite , cell viability at 72 h after irradiation significantly increased , and the percentage of sub-G1 phase cells markedly reduced comparing to the group treated with 2 Gy X-ray irradiation alone . These findings suggest that sodium selenite supplementation before irradiation could protect cells from irradiationinduced damage and reduce the percentage of apoptotic cells . Poly ADP-Ribose Polymerase ( PARP ) protein was chosen for further experiments as a principal biomarker for apoptosis . 2 Gy irradiated cells with supplementation of 50 nM sodium selenite showed increased expression levels of cleaved PARP proteins comparing to cells treated with irradiation only , although not statically significant . This indicates that sodium selenite may have the potential to inhibit irradiation-induced apoptosis in non-cancerous cells ( Puspitasari et al ., 2017 ).
The concept of osteoradionecrosis ( ORN ) was first described by Regaud in 1922 , referring to the late effect observed in individuals under RT for head and neck cancers ( O ’ Dell and Sinha , 2011 ). In addition to the impact on appearance , ORN severely affects the deglutition and linguistic function . Although the perception of the pathogenesis of ORN is not yet unified , most researchers attribute it to the fibroatrophic process featuring in early inflammation and subsequent fibrosis and remodeling caused by radiation ( Frankart et al ., 2021 ). Yamasaki et al . reported that 40 days after the 15 Gy X-ray radiation in head and neck region , all rats were anaesthetized and underwent bilateral extraction of mandibular first molars . Bone microarchitecture parameters , including total volume , bone volume , bone volume fraction ( bone volume / total volume ), trabecular number , trabecular thickness and trabecular separation were assessed 15 days and 30 days after surgery , respectively . Statistically higher trabecular separation was observed in rats treated with radiation , while a statistically higher value of the trabecular number evaluation was displayed in irradiated rats intraperitoneally administrated with sodium selenite ( 0.8 mg / kg ) 15 days after the tooth extraction . However , sodium selenite did not manifest a significant radioprotective effect in the assessment of bone microarchitecture 30 days after surgery in this experiment . Therefore , it might be fair to indicate that sodium selenite could be considered as a potential radioprotective adjuvant during locally radiation therapy with further confirmatory experiments ( Yamasaki et al ., 2019 ).
Sieber et al . found that with the supplementation of 100 mg / day of selenium in the form of sodium selenite or Se-L-Met , blood urea nitrogen ( BUN ) level of rats significantly decreased . 21 weeks after TBI , irradiated rats on sodium selenite-supplemented water showed no interstitial fibrosis and only minimal mesangiolysis in histopathological analysis while irradiated rats on standard drinking water showed severe histological abnormalities aforementioned ( Sieber et al ., 2009 ). 2 years later , they conducted further experiments and demonstrated that 2 months after TBI , BUN level of rats with supplementation of drinking water with selenium at 150 or 200 mg / d significantly decreased comparing to rats with standard drinking water . 4 months after TBI , there ’ s no difference in serum BUN level between irradiated rats with supplement of sodium selenium ( 200 mg / d ) and normal controls . Interestingly , with the supplement of 200 mg / d for 4 months , sodium selenite acted better as a kidney protective adjuvant than Se-L-Met due to its superior activity in reducing BUN level . Sodium selenite also manifested better protective effect than Se-L-Met , as it could mitigate histopathological abnormalities including cysts , sclerosed glomeruli , interstitial fibrosis , and glomerular mesangiolysis in the kidneys ( Sieber et al ., 2011 ).
Muecke et al . initiated their phase III clinical trials and one purpose of which was to estimate the radioprotective effect of sodium selenite . 81 patients suffering from uterine or cervical cancer were admitted into the trial and 39 patients were administrated sodium selenite supplementation during their RT process . During the trial , radiation-induced diarrhea , being regarded as one of the most relevant side-effects of aforementioned cancers that partly impact the quality of life , was assessed to determine whether it could be reduced by the supplementation of sodium selenite . Studies revealed that the levels of selenium were elevated both in whole blood and in serum , and the incidence of common toxicity criteria ( CTC ) Grade 2 diarrhea was significantly reduced in patients treated with sodium selenite comparing to the control group without supplementation . Notably , there was a tendency that the patients with higher Se status tolerated the radiotherapy better