Selenium Deficiency-Induced Oxidative Stress Causes Myocardial Injury in Calves by Activating Inflammation, Apoptosis, and Necroptosis

Abstract

Selenium (Se) is essential for human and animal health, but there have been few studies on the mechanisms of injury in dairy cows with Se deficiency. This study aimed to evaluate the effects of Se deficiency on myocardial injury in weaned calves. The Se-D group had significantly lower myocardial Se concentrations than the Se-C group. Histological analysis indicated that Se deficiency induced a large area of necrosis in the myocardium, accompanied by inflammatory changes. Se deficiency significantly decreased the expression of 10 of the 21 selenoprotein genes and increased the expression of SEPHS2. Furthermore, we found that oxidative stress occurred in the Se-D group by detection of redox-related indicators. Additionally, TUNEL staining showed that Se deficiency causes severe apoptosis in the myocardium, which was characterized by activating the exogenous apoptotic pathway and the mitochondrial apoptotic pathway. Se deficiency also induced necroptosis in the myocardium by upregulating MLKL, RIPK1, and RIPK3. Moreover, Se-deficient calves have severe inflammation in the myocardium. Se deficiency significantly reduced anti-inflammatory factor levels while increasing pro-inflammatory factor levels. We also found that the NF-κB pathway and MAPK pathway were activated in Se-deficient conditions. Our findings suggest that Se deficiency causes myocardial injury in weaned calves by regulating oxidative stress, inflammation, apoptosis, and necroptosis.

Oxidative Stress Induced by Selenium Deficiency Contributes to Inflammation, Apoptosis and Necroptosis in the Lungs of Calves

“…Se is an essential component as well as the active center of selenoprotein. The present study found that inadequate dietary Se led to a decrease in blood and lung Se levels in calves, and the effects of dietary Se on tissues were generally consistent with a previous study [ 20 ]. A decrease in Se is detrimental to the synthesis and activity of selenoproteins [ 22 ].…”

“…A decrease in Se is detrimental to the synthesis and activity of selenoproteins [ 22 ]. Changes in selenoprotein mRNA expression in the lungs differed slightly from the results in the hearts of selenium-deficient calves [ 20 ]. The synthesis priority and distribution differences in the organs of selenoproteins caused differences in expression levels during Se deficiency [ 23 , 24 ].…”

“…The PrimeScript RT kit (Takara, Dalian, China) was used to synthesize the cDNA in accordance with the manufacturer’s guidelines. The primer sequences were used by referring to the previous research [ 20 ]. 2× SYBR Green qPCR Master Mix was used to perform RT-qPCR assays detected with the Roche LightCycler 480II system (Basel, Switzerland).…”

“…In this study, Se-deficient calves showed significant respiratory distress and large amounts of pleural effusion accompanied by pulmonary edema and congestion during the field dissection. Although severe damage to the myocardium and heart failure were found in Se-deficient calves in a previous study [ 20 ], it has been suggested that pulmonary edema during Se deficiency may not be entirely due to heart failure [ 21 ]. Studies on the effect of Se on lung function have always focused on mice and humans, with no relevant studies in calves.…”

Nutrition and thyroid disease

“…The Recommended Dietary Allowance (RDA) of Se for healthy individuals above 50 years is 55 μg; however, the recommendation may be higher depending on the region and patients’ characteristics [13]. Se deficiency has been strongly associated with thyroid nosology, particularly with Hashimoto thyroiditis [14,15 ▪ ] and with cardiovascular diseases [16] as Se regulates inflammation, oxidative stress, apoptosis, and necroptosis [17]. Variable anticancer activity has been shown by Se supplementation in thyroid cancer patients [18].…”