Silica Nanoparticle Acute Toxicity on Male Rattus norvegicus Domestica: Ethological Behavior, Hematological Disorders, Biochemical Analyses, Hepato-Renal Function, and Antioxidant-Immune Response

Almanaa, Taghreed N.; Aref, Mohamed; Kakakhel, Mian Adnan; Elshopakey, Gehad E.; Mahboub, Heba H.; Abdelazim, Aaser M.; Kamel, Samar; Belali, Tareg M.; Abomughaid, Mosleh M.; Alhujaily, Muhanad; Fahmy, Esraa M.; Assayed, Mohamed Ezzat; Mostafa‐Hedeab, Gomaa; Daoush, Walid M.

doi:10.3389/fbioe.2022.868111

Cited by 13 publications

(5 citation statements)

References 64 publications

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“…Although alkaline phosphatase enzyme is measured to detect liver or bone toxicity, a relation to liver disease has only been described when values are increased and not decreased. [50][51][52] Furthermore, there was no alteration of other biochemical parameters and the majority of blood populations analyzed remained stable compared to the untreated control. Only, a slight increase in hematocrit, as well as eosinophils, can be observed with exposure to both BML1 and BML2 nanoformulations, which had already been described by Askri et al with an increase in the number of red blood cells, hemoglobin, and eosinophils with low doses of iron oxide nanoparticles.…”

Section: Discussionmentioning

confidence: 89%

LGR5 as a Therapeutic Target of Antibody-Functionalized Biomimetic Magnetoliposomes for Colon Cancer Therapy

Cepero,

Jiménez-Carretero,

Jabalera

et al. 2024

IJN

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Purpose The lack of specificity of conventional chemotherapy is one of the main difficulties to be solved in cancer therapy. Biomimetic magnetoliposomes are successful chemotherapy controlled-release systems, hyperthermia, and active targeting agents by functionalization of their surface with monoclonal antibodies. The membrane receptor Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) stands out as colorectal cancer (CRC) biomarker and appears to be related to treatment resistance and the development of metastasis. The aim of this study was to assess the effectiveness and safety of LGR5-targeted biomimetic magnetoliposomes loaded with oxaliplatin (OXA) or 5-fluorouracil (5-FU) in the selective treatment of CRC and their possible application in hyperthermia. Methods Synthesis, characterization and determination of heating capacity of magnetoliposomes transporting OXA or 5-FU (with and without LGR5 functionalization) were conducted. In vitro antitumoral activity was assayed in multiple colorectal cell lines at different times of exposition. In addition to this, cell internalization was studied by Prussian Blue staining, flow cytometry and fluorescence microscopy. In vivo acute toxicity of magnetoliposomes was performed to evaluate iron-related toxicity. Results OXA and 5-FU loaded magnetoliposomes functionalized with LGR5 antibody showed higher cellular uptake than non-targeted nanoformulation with a reduction of the percentage of proliferation in colon cancer cell lines up to 3.2-fold of the IC 50 value compared to that of free drug. The differences between non-targeted and targeted nanoformulations were more evident after short exposure times (4 and 8 hours). Interestingly, assays in the MC38 transduced cells with reduced LGR5 expression (MC38-L(-)), showed lower cell internalization of LGR5-targeted magnetoliposomes compared to non-transduced MC38 cell line. In addition, magnetoliposomes showed an in vitro favorable heating response under magnetic excitation and great iron-related biocompatibility data in vivo. Conclusion Drug-loaded magnetoliposomes functionalized with anti-LGR5 antibodies could be a promising CRC treatment strategy for LGR5+ targeted chemotherapy, magnetic hyperthermia, and both in combination.

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Section: Discussionmentioning

confidence: 89%

LGR5 as a Therapeutic Target of Antibody-Functionalized Biomimetic Magnetoliposomes for Colon Cancer Therapy

Cepero,

Jiménez-Carretero,

Jabalera

et al. 2024

IJN

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“…Previous studies supported this finding. For example, Almanaa et al [47] reported a noticeably increased cortisol level in male rats given SiNPs orally (125 mg/kg/d) for 4 days.…”

Section: Discussionmentioning

confidence: 99%

Magnesium Supplementation Alleviates the Toxic Effects of Silica Nanoparticles on the Kidneys, Liver, and Adrenal Glands in Rats

Badawy

Sayed-Ahmed

Almoshari

et al. 2023

Toxics

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Concerns regarding the possible hazards to human health have been raised by the growing usage of silica nanoparticles (SiNPs) in a variety of applications, including industrial, agricultural, and medical applications. This in vivo subchronic study was conducted to assess the following: (1) the toxicity of orally administered SiNPs on the liver, kidneys, and adrenal glands; (2) the relationship between SiNPs exposure and oxidative stress; and (3) the role of magnesium in mitigating these toxic effects. A total of 24 Sprague Dawley male adult rats were divided equally into four groups, as follows: control group, magnesium (Mg) group (50 mg/kg/d), SiNPs group (100 mg/kg/d), and SiNPs+ Mg group. Rats were treated with SiNPs by oral gavage for 90 days. The liver transaminases, serum creatinine, and cortisol levels were evaluated. The tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured. Additionally, the weight of the organs and the histopathological changes were examined. Our results demonstrated that SiNPs exposure caused increased weight in the kidneys and adrenal glands. Exposure to SiNPs was also associated with significant alterations in liver transaminases, serum creatinine, cortisol, MDA, and GSH. Additionally, histopathological changes were significantly reported in the liver, kidneys, and adrenal glands of SiNPs-treated rats. Notably, when we compared the control group with the treated groups with SiNPs and Mg, the results revealed that magnesium could mitigate SiNPs-induced biochemical and histopathologic changes, confirming its effective role as an antioxidant that reduced the accumulation of SiNPs in tissues, and that it returns the levels of liver transaminases, serum creatinine, cortisol, MDA, and GSH to almost normal values.

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“…These free radicals can initiate lipid peroxidation which brings about a rise in MDA levels 32 . In addition to the previously mentioned mechanism of tissue toxicity, numerous inflammatory mediators are released by various pathways, these inflammatory cytokines can magnify the toxicity 27,33 .…”

Section: Discussionmentioning

confidence: 99%

Effect of Arabic Gum (Acacia senegal) on Paracetamol-Induced Chronic Nephrotoxicity in Albino Rats

Osman¹,

Mostafa-He²,

Osman³

et al. 2022

International J. of Pharmacology

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Background and Objective: Acetaminophen (APAP), is a commonly prescribed analgesic and antipyretic drug in clinical practice. It has been reported that APAP overdose potentially induces hepatorenal damage in experimental animals and humans and in severe cases may lead to death. Acute renal failure has been reported in -1-2% of patients because of APAP overdose. This study was intended to explore the possible effects of Acacia senegal, commonly known as Arabic gum (AG) on paracetamol (N-acetyl-p-aminophenol, APAP)induced nephrotoxicity in an albino rat model. Materials and Methods: Thirty Wistar albino rats were divided into five groups, six rats each. The normal control group was administered ordinary saline orally, the APAP group received APAP intra-peritoneally for 14 days (200 mg kgG 1 ), the N-acetylcysteine (NAC) group received APAP and NAC as a standard drug orally (140 mg kgG 1 ) and the (APAP) and (AG) groups were administered APAP intraperitoneally+AG orally, in two different doses (7.5 and 15 g kgG 1 ) for 14 days. Results: Pretreatment with AG diminished urea and creatinine levels in the blood. It additionally decreased the levels of malondialdehyde (MDA) and Kidney Injury Molecule-1 (KIM-1) and compensated for the deficits in the total antioxidant capacity (TAC) and amended the APAP-induced histopathological kidney alterations. Moreover, AG increased the clearance of creatinine from the body and diminished the levels of inflammatory markers CRP, COX-2, IL-6 and IL-17 in kidney tissues induced by APAP administrations. Conclusion: Arabic gum showed a promising role in the protection against paracetamol-induced nephrotoxicity in rats.

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Silica Nanoparticle Acute Toxicity on Male Rattus norvegicus Domestica: Ethological Behavior, Hematological Disorders, Biochemical Analyses, Hepato-Renal Function, and Antioxidant-Immune Response

Cited by 13 publications

References 64 publications

LGR5 as a Therapeutic Target of Antibody-Functionalized Biomimetic Magnetoliposomes for Colon Cancer Therapy

LGR5 as a Therapeutic Target of Antibody-Functionalized Biomimetic Magnetoliposomes for Colon Cancer Therapy

Magnesium Supplementation Alleviates the Toxic Effects of Silica Nanoparticles on the Kidneys, Liver, and Adrenal Glands in Rats

Effect of Arabic Gum (Acacia senegal) on Paracetamol-Induced Chronic Nephrotoxicity in Albino Rats

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