Age-Related Reference Intervals of the Main Biochemical and Hematological Parameters in C57BL/6J, 129SV/EV and C3H/HeJ Mouse Strains

Mazzaccara, Cristina; Labruna, Giuseppe; Cito, Gennaro; Scarfò, Marzia; Felice, Mario De; Pastore, Lucio; Sacchetti, Lucia

doi:10.1371/journal.pone.0003772

Cited by 106 publications

(106 citation statements)

References 4 publications

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“…The mice receiving liposomal l-OHP showed significantly higher AST values than the control mice. However, the increased AST values observed in the mice that received liposomal l-OHP did not deviate from the standard values found in the literature, 18) and there was no significant difference in the ALT values among all groups. These results suggested that liposomal l-OHP does not induce hepatotoxicity.…”

Section: Effect Of L-ohp Encapsulated In Pegylated Liposomes On Kupffsupporting

confidence: 52%

Hepatic Tumor Metastases Cause Enhanced PEGylated Liposome Uptake by Kupffer Cells

Ukawa

Fujiwara

Ando

et al. 2016

Biological & Pharmaceutical Bulletin

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Kupffer cells in livers bearing tumor metastases were found to have promoted tumor invasion and exacerbated the metastasis. This implies that the function of Kupffer cells might differ between animals bearing hepatic metastases and those that are healthy. Kupffer cells are considered responsible for the accumulation of liposomes in the liver. In this study, we hypothesized that the alteration in the function of Kupffer cells by hepatic metastasis would also affect the biodistribution of liposomes following intravenous administration. The hepatic accumulation and the blood concentration of PEGylated liposomes were compared between healthy mice and tumor-bearing mice. We noted that hepatic accumulation and elimination from the blood were significantly accelerated in tumor-bearing mice, indicating that our hypothesis was correct. In the tumor-bearing mice, the proportion of Kupffer cells taking up liposomes was significantly increased. Intravenous injection of oxaliplatin (l-OHP) containing PEGylated liposomes decreased the fraction of Kupffer cells, but this administration caused no injury to the hepatocytes. These results suggest that PEGylated liposomes containing l-OHP may have the potential to treat metastatic hepatic cancer-not only via the direct killing of the cancer cells but also via a reduction in tumor-supportive Kupffer cells. Key words PEGylated liposome; oxaliplatin (l-OHP); liver metastasis; Kupffer cellThe liver is known as a favored site for cancer metastasis due to its abundant blood flow. The general treatment for hepatic metastases is surgical resection. Chemotherapy is usually performed for preoperative treatment, preventing recurrence after surgery, or treating nonresectable tumors. However, a prescription regimen has not been well-established for hepatic metastases, particularly from noncolorectal primaries.

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Section: Effect Of L-ohp Encapsulated In Pegylated Liposomes On Kupffsupporting

confidence: 52%

Hepatic Tumor Metastases Cause Enhanced PEGylated Liposome Uptake by Kupffer Cells

Ukawa

Fujiwara

Ando

et al. 2016

Biological & Pharmaceutical Bulletin

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“…7C). These increases did not compromise mouse survival, and the levels detected were within the range of normal values for female C57BL/6 mice, considering age and the blood extraction method [58,59]. Biochemical analysis of urine showed normal results at all times for all parameters analyzed (Table 1).…”

Section: In Vivo Toxic Effects Of Dmsa-mnpmentioning

confidence: 68%

Long term biotransformation and toxicity of dimercaptosuccinic acid-coated magnetic nanoparticles support their use in biomedical applications

Mejías

Gutiérrez

Salas

et al. 2013

Journal of Controlled Release

117

106

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Although iron oxide magnetic nanoparticles (MNP) have been proposed for numerous biomedical applications, little is known about their biotransformation and long-term toxicity in the body. Dimercaptosuccinic acid (DMSA)-coated magnetic nanoparticles have been proven efficient for in vivo drug delivery, but these results must nonetheless be sustained by comprehensive studies of long-term distribution, degradation and toxicity. We studied DMSA-coated magnetic nanoparticles effects in vitro on NCTC 1469 nonparenchymal hepatocytes, and analyzed their biodistribution and biotransformation in vivo in C57BL/6 mice. Our results indicate that DMSA-coated magnetic nanoparticles have little effect on cell viability, oxidative stress, cell cycle or apoptosis on NCTC 1469 cells in vitro. In vivo distribution and transformation was studied by alternating current magnetic susceptibility measurements, a technique that permits distinction of MNP from other iron species. Our results show that DMSA-coated MNP accumulate in spleen, liver and lung tissues for extended periods of time, in which nanoparticles undergo a process of conversion from superparamagnetic iron oxide nanoparticles to other nonsuperparamagnetic iron forms, with no significant signs of toxicity.

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“…Even though BUN levels were slightly lower than the reference values, there were no significant differences between the saline and particle groups. Variations in normal BUN levels have been previously reported to be mouse strain-dependent (34,35,43).…”

Section: Kidney Histological Evaluation and Renal Functionmentioning

confidence: 91%

“…Toxicological biomarkers analyzed included blood urea nitrogen (BUN), albumin, alkaline phosphatase (Alk Phos), alanine aminotransferase (ALT), serum creatinine, glucose, total bilirubin, cholesterol, and total triglycerides. Normal range values for these biomarkers were obtained from the Laboratory and compared with those in the literature (34,35).…”

Section: Serum Biomarker Analysismentioning

confidence: 99%

Safety and Biocompatibility of Carbohydrate-Functionalized Polyanhydride Nanoparticles

Vela-Ramirez

Goodman

Boggiatto

et al. 2014

AAPS J

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ABSTRACT. Carbohydrate functionalization of nanoparticles allows for targeting of C-type lectin receptors. This family of pattern recognition receptors expressed on innate immune cells, such as macrophages and dendritic cells, can be used to modulate immune responses. In this work, the in vivo safety profile of carbohydrate-functionalized polyanhydride nanoparticles was analyzed following parenteral and intranasal administration in mice. Polyanhydride nanoparticles based on 1,6-bis-(pcarboxyphenoxy)hexane and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane were used. Nanoparticle functionalization with di-mannose (specifically carboxymethyl-α-D-mannopyranosyl-(1,2)-Dmannopyranoside), galactose (specifically carboxymethyl-β-galactoside), or glycolic acid induced no adverse effects after administration based on histopathological evaluation of liver, kidneys, and lungs. Regardless of the polymer formulation, there was no evidence of hepatic or renal damage or dysfunction observed in serum or urine samples. The histological profile of cellular infiltration and the cellular distribution and kinetics in the lungs of mice administered with nanoparticle treatments followed similar behavior as that observed in the lungs of animals administered with saline. Cytokine and chemokine profiles in bronchoalveolar lavage fluid indicated surface chemistry dependence on modest secretion of IL-6, IP-10, and MCP-1; however, there was no evidence of any deleterious histopathological changes. Based on these analyses, carbohydrate-functionalized nanoparticles are safe for in vivo applications. These results provide foundational information towards the evaluation of the capabilities of these surface-modified nanoparticles as vaccine delivery formulations.

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Age-Related Reference Intervals of the Main Biochemical and Hematological Parameters in C57BL/6J, 129SV/EV and C3H/HeJ Mouse Strains

Cited by 106 publications

References 4 publications

Hepatic Tumor Metastases Cause Enhanced PEGylated Liposome Uptake by Kupffer Cells

Hepatic Tumor Metastases Cause Enhanced PEGylated Liposome Uptake by Kupffer Cells

Long term biotransformation and toxicity of dimercaptosuccinic acid-coated magnetic nanoparticles support their use in biomedical applications

Safety and Biocompatibility of Carbohydrate-Functionalized Polyanhydride Nanoparticles

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