No abstract

Cisplatin (cis-diamminedichloroplatinum II, CIS) is a potent and widely used chemotherapeutic agent to treat various malignancies, but its therapeutic use is limited because of the dose-dependent nephrotoxicity. Cell death and inflammation play key role in the development and progression of CIS-induced nephropathy. Sulforaphane (SFN), a natural constituent of cruciferous vegetables such as broccoli, Brussels sprouts, etc., has been shown to exert various protective effects in models of tissue injury and cancer. In this study, we have investigated the role of pro-survival, cell death and inflammatory signaling pathways using a rodent model of CIS-induced nephropathy, and explored the effects of SFN on these processes. Cisplatin triggered marked activation of stress signaling pathways (p53, Jun N-terminal kinase (JNK), and p38-α MAPK) and promoted cell death in the kidneys (increased DNA fragmentation, caspases-3/7 activity, TUNEL), associated with attenuation of various pro-survival signaling pathways (e.g. extracellular signal-regulated kinase (ERK) and p38-β MAPK). Cisplatin also markedly enhanced inflammation in the kidneys (promoted NF-κB activation, increased expression of adhesion molecules ICAM and VCAM, enhanced tumor necrosis factor-alpha (TNF-α) levels, and inflammatory cell infiltration). These effects were significantly attenuated by pre-treatment of rodents with SFN. Cisplatin-induced nephropathy is associated with activation of various cell death and pro-inflammatory pathways (p53, JNK, p38-α, TNF-α, and NF-κB) and impairments of key pro-survival signaling mechanisms (ERK and p38-β). SFN is able to prevent the CIS-induced renal injury by modulating these pathways, providing a novel approach for preventing this devastating complication of the chemotherapy.

Hydroxyapatite (HAP) has been the gold standard in the biomedical field due to its composition and similarity to human bone. Properties such as shape, size, morphology, and ionic substitution can be tailored through the use of different synthesis techniques and compounds. Regardless of the ability to determine its physicochemical properties, a conclusion for the correlation with the biological response it is yet to be found. Hence, a special focus on the most desirable properties for an appropriate biological response needs to be addressed. This review provides an overview of the fundamental properties of hydroxyapatite nanoparticles and the characterization of physicochemical properties involved in their biological response and role as a drug delivery system. A summary of the main chemical properties and applications of hydroxyapatite, the advantages of using nanoparticles, and the influence of shape, size, functional group, morphology, and crystalline phase in the biological response is presented. A special emphasis was placed on the analysis of chemical and physical interactions of the nanoparticles and the cargo, which was explained through the use of spectroscopic and physical techniques such as FTIR, Raman, XRD, SEM, DLS, and BET. We discuss the properties tailored for hydroxyapatite nanoparticles for a specific biomolecule based on the compilation of studies performed on proteins, peptides, drugs, and genetic material.