ABSTRACT
Due to their dynamic characteristics, hydroxyapatite nanoparticles (HAP-NPs) have been employed numerous times in nanomedicine and in tissue engineering, particularly as diagnostic and therapeutic agents. However, there are outstanding findings from various studies that question whether these NPs are safe when they are used in the human body. Therefore, a more in-depth toxicity assessment should be carried out to give a clear answer regarding the fate of these particles. Here we aim to investigate the possible cytotoxicity, genotoxicity and inflammation induced by HAP-NPs, as well as predict the synergistic antioxidative effect of chitosan nanoparticles (CsNPs) and curcumin nanoparticles (CurNPs) in mitigating this pronounced toxicity. The present study was conducted on eighty Wistar male rats, divided into eight equal groups. The results showed that, at the molecular level, HAP-NPs significantly induced gene expression of tumor suppressor protein p53, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and also Kidney Injury Molecule-1 (KIM-1) and Lipocalin-2 (LCN2). In addition, kidney biochemical parameters (total bilirubin, urea, uric acid and creatinine) increased, but albumin levels decreased in the group treated with HAP-NPs alone. Meanwhile, co-treatment with CsNPs and/or CurNPs with HAP-NPs showed an improvement in the activities of the kidney parameters and reduced inflammation. This study shows that the nephrotoxicity mechanism of HAP-NPs may involve various signaling pathways including alterations in biochemical parameters, gene expression of KIM-1 and LCN2 and disturbing the production of cytokines and p53. Furthermore, these insights showed that the combined effect of both CsNPs and CurNPs was more pronounced than the effect of each one on its own.
ABSTRACT
The clinical use of cisplatin is highly limited, because of its renal toxicity. In this study, the protective effect of grape seed proanthocyanidin extract (GSPE) against cisplatin-induced nephrotoxicity is investigated in rats. Results showed that DNA qualitative analysis indicated an increase in the instability of the DNA purified from the cisplatin exposed kidney cells. Agarose gel electrophoresis revealed DNA damage in the form of smearing as well as ladder like fragmentation of the kidney genomic DNA. Cisplatin produced different RAPD patterns compared to control. Deletion of bands for the amplified DNA extracted from cisplatin treated rats was the most common outcome. Treatment with cisplatin decreased albumin, and increased urea and creatinine. Cisplatin significantly increased the level of kidney free radicals, and decreased the glutathione content and the activities of the antioxidant enzymes. The presence of GSPE with cisplatin significantly alleviated its nephrotoxicity. In conclusion, the present study showed that cisplatin induced damage in the kidney genomic DNA, lipid peroxidation, inhibition of antioxidant enzymes and alterations of biochemical parameters in plasma and kidney of rats. While, GSPE treatment protected against the toxic effects induced by cisplatin. Thus, GSPE may be used to prevent toxicity during chemotherapeutic treatment with cisplatin.
