Protective effect of spore oil-functionalized nano-selenium system on cisplatin-induced nephrotoxicity by regulating oxidative stress-mediated pathways and activating immune response

Abstract

In clinical practice, cisplatin is the most commonly used chemotherapy drug to treat a range of malignancies. Severe ROS-regulated nephrotoxicity, however, restricts its applicability. Currently, the main mechanisms leading to cisplatin-induced nephrotoxicity in clinical settings involve hydration or diuresis. However, not all patients can be treated with massive hydration or diuretics. Therefore, it is crucial to develop a treatment modality that can effectively reduce nephrotoxicity through a foodborne route. Selenium has been reported to have strong antioxidant as well as anticancer effects when administered as spore oil. Herein, we established cellular and animal models of cisplatin-induced nephrotoxicity and synthesized spore oil-functionalized nano-selenium (GLSO@SeNPs). We found that GLSO@SeNPs inhibit the mitochondrial apoptotic pathway by maintaining oxidative homeostasis and regulating related signaling pathways (the MAPK, caspase, and AKT signaling pathways). In vivo, GLSO@SeNPs could effectively improve cisplatin-induced renal impairment, effectively maintaining oxidative homeostasis in renal tissues and thus inhibiting the process of renal injury. In addition, GLSO@SeNPs were converted into selenocysteine (SeCys2), which may exert protective effects. Furthermore, GLSO@SeNPs could effectively modulate the ratio of immune cells in kidneys and spleen, reducing the proportions of CD3+CD4+ T cells, CD3+CD8+ T cells, and M1 phenotype macrophages and increasing the proportion of anti-inflammatory regulatory T cells. In summary, in this study, we synthesized food-derived spore oil-functionalized nanomaterials, and we explored the mechanisms by which GLSO@SeNPs inhibit cisplatin-induced nephrotoxicity. Our study provides a basis and rationale for the inhibition of cisplatin-induced nephrotoxicity by food-derived nutrients.

Dietary fat supplementation relieves cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis in pigs

“…This confirms the critical role of dietary fat supplementation in alleviating cold temperature-induced oxidative stress and damage. The mitochondrial oxidative stress pathway and the ER stress pathway mediate apoptosis simultaneously, and the alleviation of oxidative stress may indicate a decrease in apoptosis [ 60 , 61 ]. Therefore, we measured the expression of apoptosis-related genes and proteins in the liver.…”

Histological Assessment of Selenium Protective Effect Against Diclofenac Sodium-Induced Nephrotoxicity in Rats

“…Sodium Selenite (Na 2 SeO 3 ) is an antioxidant that requires bioconversion (reduction) in the organism before it can perform its function [30]. The reduction of selenite to selenide (from Se +4 to Se -2 ) involves several steps.…”

“…has renoprotective activity against nephrotoxicity induced by several chemicals [27][28][29][30] and has been effective in preventing ischemic renal failure [31]. However, the efficacy of selenium in preventing AKI and associated morbidity and mortality after off-pump coronary bypass graft surgery is controversial, as a recent article reported conflicting results [32].…”