Cisplatin is a chemotherapy agent commonly used to treat a wide variety of cancers. Despite the potential for both severe acute and chronic side effects, it remains a preferred therapeutic option for many malignancies due to its potent anti-tumor activity. Common cisplatin-associated side-effects include acute kidney injury (AKI) and chronic kidney disease (CKD). These renal injuries may cause delays and potentially cessation of cisplatin therapy and have long-term effects on renal function reserve. Thus, developing mechanism-based interventional strategies that minimize cisplatin-associated kidney injury without reducing efficacy would be of great benefit. In addition to its action of cross-linking DNA, cisplatin has been shown to affect mitochondrial metabolism, resulting in mitochondrially derived reactive oxygen species (ROS). Increased ROS formation in renal proximal convoluted tubule cells is associated with cisplatin-induced AKI and CKD. We review the mechanisms by which cisplatin may induce AKI and CKD and discuss the potential of mitochondrial superoxide dismutase mimetics to prevent platinum-associated nephrotoxicity.

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Pharmacological ascorbate (i.e., intravenous infusions of vitamin C reaching ~ 20 mM in plasma) is under active investigation as an adjuvant to standard of care anti-cancer treatments due to its dual redox roles as an antioxidant in normal tissues and as a prooxidant in malignant tissues. Immune checkpoint inhibitors (ICIs) are highly promising therapies for many cancer patients but face several challenges including low response rates, primary or acquired resistance, and toxicity. Ascorbate modulates both innate and adaptive immune functions and plays a key role in maintaining the balance between pro and anti-inflammatory states. Furthermore, the success of pharmacological ascorbate as a radiosensitizer and a chemosensitizer in pre-clinical studies and early phase clinical trials suggests that it may also enhance the efficacy and expand the benefits of ICIs.

The aim of this study was to investigate the hypoglycemic and antioxidant effect of Curcumin Copper Oxide nano-composite in STZ-induced diabetic rats. Sixty male rats were divided into four equal groups. Group 1 (control) comprised 15 rats received no drugs, Group 2 (Diabetic nontreated group) included 15 rats received no drugs, serve as STZ induced diabetic group. Group 3 (Diabetic nano-curcumin treated group) consists of 15 rats, received curcumin nanoparticle orally at a dose level of 2 mg/kg b.wt/day. Group 4 (Diabetic Curcumin Copper Oxide Nano-Composite treated group): included 15 rats, received curcumin Copper Oxide Nano-Composite at a dose level of 7 mg/kg b.wt/day orally. The obtained results revealed that, diabetic rats showed significant increase in serum glucose and Malondialehyde (MDA) concentrations. However, serum Superoxide dismutase (SOD) activity, Reduced Glutathione (GSH) and insulin concentration in pancreatic tissue were markedly decreased. Moreover, a significant down regulation in Insulin Receptor-A (IRA) and Insulin Receptors Substrate-2 (IRs-2) mRNA gene levels in hepatic tissue were observed in diabetic rats. Administration of Curcumin Copper Oxide Nano-Composite in diabetic rats caused significant improvement of all previous parameters. These results suggested that, Curcumin Copper Oxide Nano-Composite treatment may decrease the diabetic complications as hyperglycemia and oxidative stress in rats through free radical scavenging as well as regulation of endogenous antioxidant defense system mechanisms.

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