Chitosan and Curcumin Nanoformulations against Potential Cardiac Risks Associated with Hydroxyapatite Nanoparticles in Wistar Male Rats.

Nanoparticle-induced cardiovascular diseases have attracted much attention. Upon entering the blood circulation system, these particles have the potency to induce cardiomyocytes, leading to cardiac failure or myocardial ischemia, and the molecular mechanism remains to be completely clarified. In this study, the cardiac toxicity of rats orally exposed to hydroxyapatite nanoparticles (HAPNPs) has been observed through an increase in myocardial infarction serum markers including CK-MB and alterations in routine blood factors, expression of apoptosis-related protein P53, and increased levels of serum inflammatory markers represented by the tumor necrosis factor alpha and Interleukin-6, as well as a decline in heart antioxidant enzymes and reduced glutathione level, while an induction in lipid peroxidation and nitric oxide has been observed, as well as notable histological and histochemical alterations in the heart of these animals. mRNA and protein expressions of vascular endothelial growth factor (VEGF-A), cyclooxygenase-2 (COX-2), and atrial natriuretic factor (ANF) were elevated in the myocardium. However, the coadministration of chitosan nanoparticles (CsNPs) and/or curcumin nanoparticles (CurNPs) successfully modulated these alterations and induced activation in antioxidant parameters. The present data suggest that HAPNPs-induced apoptosis via the mitochondrial pathway may play a crucial role in cardiac tissue damage and the early treatment with CsNPs and CurNPs may protect the heart from infarction induced by HAPNPs toxic effect.

Bio-evaluation of the role of chitosan and curcumin nanoparticles in ameliorating genotoxicity and inflammatory responses in rats' gastric tissue followed hydroxyapatite nanoparticles' oral uptake.

Hydroxyapatite has been extensively used in tissue engineering due to its osteogenic potency, but its present toxicological facts are relatively insufficient. Here, the possible gastric toxicity of hydroxyapatite nanoparticles was evaluated biochemically to determine oxidant and antioxidant parameters in rats' stomach tissues. At results, hydroxyapatite nanoparticles have declined stomach antioxidant enzymes and reduced glutathione level, while an induction in lipid peroxidation and nitric oxide has been observed. Furthermore, DNA oxidation was analyzed by the suppression of toll-like receptors 2, nuclear factor-kappa B and Forkhead box P3 gene expression and also 8-Oxo-2'-deoxyguanosine level as a genotoxicity indicator. Various pro-inflammatory gene products have been identified that intercede a vital role in proliferation and apoptosis suppression, among these products: tumor suppressor p53, tumor necrosis factor-α and interliukin-6. Moreover, the hydroxyapatite-treated group revealed wide histological alterations and significant elevation in the number of proliferating cell nuclear antigen-positive cells, which has been observed in the mucosal layer of the small intestine, and these alterations are an indication of small intestine injury, while the appearance of chitosan and curcumin nanoparticles in the combination group showed improvement in all the above parameters with inhibition of toxic-oxidant parameters and activation of antioxidant parameters.

The protective role of CsNPs and CurNPs against DNA damage, oxidative stress, and histopathological and immunohistochemical alterations induced by hydroxyapatite nanoparticles in male rat kidney.

Hydroxyapatite nanoparticles (HAP-NPs) are an inorganic component of natural bone and are mainly used in the tissue engineering field due to their bioactivity, osteoconductivity, biocompatibility, non-inflammatory, and non-toxicity properties. However, the current toxicity data for HAP-NPs regarding human health are limited, and only a few results from basic studies have been published. Therefore, the present study was designed to investigate the beneficial role of chitosan nanoparticles (CsNPs) and curcumin nanoparticles (CurNPs) in alleviating nephrotoxicity induced by HAP-NPs in male rats. The results showed that HAP-NPs caused a reduction in antioxidant enzymes and induced lipid peroxidation, nitric oxide production and DNA oxidation. Moreover, HAP-NP administration was associated with intense histologic changes in kidney architecture and immunoreactivity to proliferating cell nuclear antigen (PCNA). However, the presence of CsNPs and/or CurNPs along with HAP-NPs reduced the levels of oxidative stress through improving the activities of antioxidant enzymes. Also, the rats administered the nanoparticles showed a moderate improvement in glomerular damage which matched that of the control group and showed mild positive reactions to PCNA-ir in glomeruli and renal tubules in the cortical and medullary portions. These novel insights confirm that the presence of chitosan and curcumin in nanoforms has powerful biological effects with enhanced bioactivity and bioavailability phenomena compared to their microphase counterparts. Also, they were able to ameliorate the nephrotoxicity induced by HAP-NPs.

Synergistic antioxidant capacity of CsNPs and CurNPs against cytotoxicity, genotoxicity and pro-inflammatory mediators induced by hydroxyapatite nanoparticles in male rats.

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.