Protective Role of Selenium and High Dose Vitamin E against Cisplatin - Induced Nephrotoxicty in Rats

Abstract

Background: Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer. We investigated the effect of selenium (Se) with high dose vitamin E (VE) administration to prevent CDDP-induced nephrotoxicity in rats. Materials and Methods: In this study, 40 female Wistar rats were randomly divided into five equal groups. The first group, which served as the control, was administered physiological saline (2.5 cc/day, 5 days) intraperitoneally (IP), while group A was administered cisplatin (6 mg/kg BW/ single dose) plus physiological saline IP. Groups B, C, D received IP five doses of Se (1.5 mg/kg BW), and a high dose of VE (1000 mg/kg BW) (Se-VE) in combination before, simultaneously, and after CDDP, respectively. The rats were sacrificed five days after CDDP administration. Plasma malondialdehide (MDA), glutathione peroxidase (GSH-Px), reduced glutathione (GSH), catalase, urea, creatinine levels, renal histopathological changes were measured. Results: The histopathological injury score, plasma levels of MDA, urea, creatinine were found to increase in group A compared to the control (p<0.05), while plasma levels of GSH-Px, GSH and catalase decreased (p<0.05). In contrast, plasma levels of MDA decreased (p<0.05) in groups B, C, D, which were treated with Se-VE, whereas levels of GSH-Px, GSH were found to increase only for group D (p<0.05). Plasma urea, creatinine levels improved in the treatment groups compared to group A (p<0.001). Histopathological changes caused by CDDP were also significantly improved after Se-VE treatment (p<0.05). Conclusions: Oxidative stress increases with CDDP-induced nephrotoxicity in rats. Se-VE supplementation might thus play a role in the prevention of CDDP-induced nephrotoxicity in patients.

Treatment with melatonin and selenium attenuates docetaxel‐induced apoptosis and oxidative injury in kidney and testes of mice

“…In addition, there is a relationship between prostate cancer and tissue vitamin E (α‐tocopherol and γ‐tocopherol) concentrations in humans, although their concentrations were modulated in patients with prostate cancer (Albanes et al, ). In addition, several chemotherapeutic agents such as cisplatin (Aksoy et al, ; Nazıroğlu et al, ) and oxaliplatin (Di Cesare, Zanardelli, Failli, & Ghelardini, ) decreased tissue tocopherol concentrations in rodents. In addition to the R‐GSH and GSHPx analyses, we decided to investigate protective roles of MEL and Se treatments on DTX‐induced changes in α‐ and γ‐tocopherol concentrations in the kidney samples.…”

“…γ‐tocopherol, the most common form of vitamin E in the United States diets, may be a more potent pro‐apoptotic agent than α‐tocopherol in trapping ROS in cancers (Albanes et al, ). It is well established that MEL is a strong antioxidant, and it has also been shown to act synergistically with α‐tocopherol, γ‐tocopherol and R‐GSH and stimulates the antioxidant α‐tocopherol, γ‐tocopherol, R‐GSH concentrations and GSHPx activity (Aksoy et al, ; Bejarano et al, ; Kahya et al, ; Nazıroğlu et al, ). Cisplatin‐induced decreases in α‐tocopherol concentrations were reported in kidney of rats (Aksoy et al, ; Bejarano et al, ; Kahya et al, ; Nazıroğlu et al, ).…”

“…The presence of an inverse relationship between plasma Se levels and mortality in patients with prostate cancer treated with/without taxanes has been reported (Niraula et al, ). Recent studies have demonstrated the protective role of Se on cisplatin‐induced oxidative stress and apoptosis in kidneys (Aksoy et al, ; Nazıroğlu, Karaoğlu, & Aksoy, ; Saif‐Elnasr, Abdel‐Aziz, & Ibrahim, ) and testes (Simsek et al, ) in rats. In addition, synergic interaction between Se and chemotherapeutic agent (cisplatin) on the same intracellular toxic cascade in breast cancer cell line was recently reported (Sakallı Çetin, Nazıroğlu, Çiğ, Övey, & Aslan, ).…”

Peer Review #1 of "Oxidative stress as a potential target in acute kidney injury (v0.1)"

“…Vitamin C redox is preserved by diverse components of redox systems in the cell, reacting with oxidized forms of molecules (enzymes, free radicals) 21 . Selenium (Se) represents a trace element that plays a role in cellular aerobic respiration by reducing free radicals 85 . Selenium deficiency was linked to AKI in rodent model 86 .…”

Novel Therapies for Acute Kidney Injury

“…Selenium is a trace element that is involved in the reduction of free radicals during cellular aerobic respiration. 82 Deficiency in selenium has been linked to AKI in rat models. 83 Selenium supplementation correlated with improved serum creatinine, urea, and histopathological evidence in cisplatin-induced kidney injury in rats.…”