Raloxifene Protects Cisplatin-Induced Renal Injury in Mice via Inhibiting Oxidative Stress

Abstract

Purpose Cisplatin is one of the most widely used antineoplastic drugs but has limited therapeutic effects due to nephrotoxicity. The aim of this study was to determine the possible renoprotective effect of the antioxidant raloxifene on cisplatin-induced nephrotoxicity in mice. Materials and Methods Cisplatin-induced acute renal injury was established in female C57 mice that were treated with saline (normal control) or raloxifene over a 7-day period. The body weight of the mice was recorded. Histopathological examinations of the kidney tissues were performed using H&E, PAS staining and TEM. The histomorphology of liver and other organs was observed by H&E staining. The serum levels of creatinine, blood urea nitrogen (BUN), alanine transaminase (ALT) and glutamic oxalacetic transaminase (AST) were analyzed by specific kits. Superoxide dismutase (SOD) and glutathione (GSH) activity, and the content of malondialdehyde (MDA) in the kidney, liver homogenates and HK-2 cells were measured by WST-8 and thiobarbituric acid colorimetric methods. Moreover, the mitochondrial structures of HK-2 cells were performed using TEM. The viability and proliferation of HK-2 cells were examined by CCK-8 and EdU incorporation assays. The mitochondrial membrane potential was measured by JC-1 fluorescence. Results Raloxifene significantly reduced the levels of serum creatinine, urea, ALT and AST in the cisplatin-treated mice, and alleviated cisplatin-induced renal and hepatic tissue injury. Furthermore, raloxifene also increased the activity of GSH and SOD in the renal tissues and HK-2 cells, and reduced MDA levels, thereby limiting oxidative stress in the kidney. Conclusion Raloxifene protected against cisplatin-induced nephrotoxicity by activating the antioxidant system, along with alleviating liver damage. It should be considered as a potential adjuvant in cisplatin-based chemotherapeutic protocols.

Ranolazine reduces oxidative damage and improves kidney function in cisplatin-induced nephrotoxicity

“…Additionally, inflammation and apoptosis were responsible for CIS-induced renal damage [36]. Our findings were consistent with their results, as MDA levels were among the increased oxidant parameters in CISadministered rats [37,38]. Furthermore, a study examining the antidiabetic effect of RAN demonstrated a significant decrease in MDA levels in pancreatic tissue [39].…”

Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer

“…This result contrasts with previously published data demonstrating the antioxidative features of raloxifene (1), indicating the dual nature of raloxifene depending on cell specificity. 50,51 Concurrently with the observed increase in the granularity of the cellular cytoplasm through flow cytometry, supravital staining of the same cell line with acridine orange after a 72-hour treatment with raloxifene (1) or bipyraloxifene (2) resulted in a significant augmentation in the presence of autophagosomes, indicating a heightened autophagic process in response to the treatment (Fig. 3A).…”

“…This result contrasts with previously published data demonstrating the antioxidative features of raloxifene ( 1 ), indicating the dual nature of raloxifene depending on cell specificity. 50,51…”

The diminution and modulation role of water-soluble gallic acid-carboxymethyl chitosan conjugates against the induced nephrotoxicity with cisplatin

“…Changes in the body and kidney weights of rats from all groups were observed and renal index (%) was calculated according to the formula: (kidney weight/total body weight) × 100 33 .…”