Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease

Anwar, Fareeha; Saleem, Uzma; Rehman, Atta-Ur; Ahmad, Bashir; Froeyen, Matheus; Mirza, Muhammad Usman; Kee, Lee Yean; Abdullah, Iskandar; Ahmad, Sarfraz

doi:10.3389/fphar.2021.607026

Cited by 14 publications

(20 citation statements)

References 44 publications

(53 reference statements)

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“…Many regulations are in place for prior pre-clinical studies regarding the safety of new compounds (Aslam and Ahmed, 2016). To ensure the safety of humans from the lethal effects of the test compounds, a toxicological evaluation of the test compound is carried out which follows standard protocols set forth by regulatory bodies (Anwar et al, 2021b). The protocols strictly emphasize the safety of the human population which regulates the laws regarding the toxicological evaluation of all test compounds prior to their approval.…”

Section: Discussionmentioning

confidence: 99%

“…Benefits of toxicological evaluation of plant extracts in animal models also include a controlled exposure time, examination of different tissues for possible harms, and determining the effect on different biomarkers (Arome and Chinedu, 2013). Conclusively, the toxicity study beneficially demarcates between toxic dose and therapeutic dose (Anwar et al, 2021b). Animal models are recommended for executing toxicological evaluations which comply with the organization of economic cooperation and development (OECD) guidelines.…”

Section: Introductionmentioning

confidence: 99%

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Phytochemical and toxicological evaluation of Zephyranthes citrina

Rehman

Saleem

Ahmad³

et al. 2022

Front. Pharmacol.

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Drugs obtained from medicinal plants have always played a pivotal role in the field of medicine and to identify novel compounds. Safety profiling of plant extracts is of utmost importance during the discovery of new biologically active compounds and the determination of their efficacy. It is imperative to conduct toxicity studies before exploring the pharmacological properties and perspectives of any plant. The present work aims to provide a detailed insight into the phytochemical and toxicological profiling of methanolic extract of Zephyranthes citrina (MEZ). Guidelines to perform subacute toxicity study (407) and acute toxicity study (425) provided by the organization of economic cooperation and development (OECD) were followed. A single orally administered dose of 2000 mg/kg to albino mice was used for acute oral toxicity testing. In the subacute toxicity study, MEZ in doses of 100, 200, and 400 mg/kg was administered orally, consecutive for 28 days. Results of each parameter were compared to the control group. In both studies, the weight of animals and their selected organs showed consistency with that of the control group. No major toxicity or organ damage was recorded except for some minor alterations in a few parameters such as in the acute study, leukocyte count was increased and decreased platelet count, while in the subacute study platelet count increased in all doses. In the acute toxicity profile liver enzymes Alanine aminotransferase (ALT), as well as, aspartate aminotransferase (AST) were found to be slightly raised while alkaline phosphatase (ALP) was decreased. In subacute toxicity profiling, AST and ALT were not affected by any dose while ALP was decreased only at doses of 200 and 400 mg/kg. Uric acid was raised at a dose of 100 mg/kg. In acute toxicity, at 2000 mg/kg, creatinine and uric acid increased while urea levels decreased. Therefore, it is concluded that the LD50 of MEZ is more than 2000 mg/kg and the toxicity profile of MEZ was generally found to be safe.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phytochemical and toxicological evaluation of Zephyranthes citrina

Rehman

Saleem

Ahmad³

et al. 2022

Front. Pharmacol.

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“…Oxidative stress is considered to be one of the potential triggers for the onset of AD, a state in which the antioxidant defense levels are out of balance with free radicals, which induces potential brain damage (Tönnies & Trushina, 2017 ). There is evidence that oxidative stress occurs prior to the appearances of senile plaques and neurofibrillary tangles, which contributes to the progression of AD symptoms (Anwar et al., 2021 ). Glutathione peroxidase is an important antioxidant in the body, which can scavenge free radicals and exert antioxidant effects, while MDA is a lipid metabolite, which is the main degradation product of lipid peroxidation, and it can be used as an indicator that brain tissue is attacked by free radicals (Wang et al., 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer’s disease

et al. 2022

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The blood–brain barrier (BBB) is a protective barrier for brain safety, but it is also a major obstacle to the delivery of drugs to the cerebral parenchyma such as the hippocampus, hindering the treatment of central nervous system diseases such as Alzheimer’s disease (AD). In this work, an anti-AD brain-targeted nanodrug delivery system by co-loading icariin (ICA) and tanshinone IIA (TSIIA) into Aniopep-2-modified long-circulating (Ang2-ICA/TSIIA) liposomes was developed. Low-density lipoprotein receptor-related protein-1 (LRP1) was a receptor overexpressed on the BBB. Angiopep-2, a specific ligand of LRP1, exhibited a high binding efficiency with LRP1. Additionally, ICA and TSIIA, drugs with neuroprotective effects are loaded into the liposomes, so that the liposomes not only have an effective BBB penetration effect, but also have a potential anti-AD effect. The prepared Ang2-ICA/TSIIA liposomes appeared narrow dispersity and good stability with a diameter of 110 nm, and a round morphology. Cell uptake observations, BBB models in vitro , and imaging analysis in vivo showed that Ang2-ICA/TSIIA liposomes not only penetrate the BBB through endocytosis, but also accumulate in N2a cells or brain tissue. The pharmacodynamic analysis in vivo demonstrated that Ang2-ICA/TSIIA liposomes could improve AD-like pathological features in APP/PS1 mice, including inhibiting neuroinflammation and oxidative stress, reducing apoptosis, protecting neurons, and improving cognitive function. Therefore, Ang2-ICA/TSIIA liposomes are considered a potentially effective therapeutic strategy for AD.

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“…The basic objective behind toxicity studies is to find out the safety levels of the drugs. 50 The drugs selected in this study are marketed drugs and passed out all the toxicity profiling. In this study, analysis of hematological and biochemical studies was conducted on the doses that were selected for therapeutic effect.…”

Section: Discussionmentioning

confidence: 99%

Parkinsonism Attenuation by Antihistamines via Downregulating the Oxidative Stress, Histamine, and Inflammation

et al. 2022

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Parkinson disease (PD) is a neurodegenerative disorder of the motor activity of the brain, regulated by dopaminergic neurons of substantia nigra, resulting in an increased density of histaminergic fibers. This study was aimed to evaluate the effects of H1 antagonist’s ebastine and levocetirizine in PD per se and in combination. Animals were divided into 9 groups ( n = 10). Group 1 received carboxymethyl cellulose CMC (1 mL/kg). Group II was treated with haloperidol (1 mg/kg) (diseased group). Group III was treated with levodopa/carbidopa (levo 20 mg/kg). Groups IV and V were treated with ebastine at dose levels of 2 and 4 mg/kg, respectively. Groups VI and VII were treated with levocetirizine at dose levels of 0.5 and 1 mg/kg, respectively. Group VIII was treated with ebastine (4 mg/kg) + levo (20 mg/kg) in combination. Group IX was treated with levocetirizine (1 mg/kg) + levo (20 mg/kg). PD was induced with haloperidol (1 mg/kg iv, once daily for 23 days) for a duration of 30 min. Behavioral tests like rotarod, block and triple horizontal bars, actophotometer, and open field were performed. Biochemical markers of oxidative stress, i.e., SOD, CAT, GSH, MDA, dopamine, serotonin, and nor-adrenaline and nitrite, were determined. Histamine, mRNA expression of α-synuclein, and TNF-α level in the serum and brain of mice were analyzed. Endogenous biochemical markers were increased except mRNA expression of α-synuclein, which was reduced. In combination therapy with the standard drug, ebastine (4 mg/kg) significantly improved the cataleptic state and dopamine levels, but no significant difference in the renal and liver functioning tests was observed. This study concluded that ebastine (4 mg/kg) might work in the treatment of PD as it improves the cataleptic state in haloperidol-induced catalepsy.

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Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease

Cited by 14 publications

References 44 publications

Phytochemical and toxicological evaluation of Zephyranthes citrina

Phytochemical and toxicological evaluation of Zephyranthes citrina

Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer’s disease

Parkinsonism Attenuation by Antihistamines via Downregulating the Oxidative Stress, Histamine, and Inflammation

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