PMID- 35126145
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220208
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Acute Oral, Subacute, and Developmental Toxicity Profiling of Naphthalene 2-Yl, 
      2-Chloro, 5-Nitrobenzoate: Assessment Based on Stress Response, Toxicity, and 
      Adverse Outcome Pathways.
PG  - 810704
LID - 10.3389/fphar.2021.810704 [doi]
LID - 810704
AB  - The U.S. National Research Council (NRC) introduced new approaches to report 
      toxicity studies. The NRC vision is to explore the toxicity pathways leading to 
      the adverse effects in intact organisms by the exposure of the chemicals. This 
      study examines the toxicity profiling of the naphthalene-2-yl 
      2-chloro-5-dinitrobenzoate (SF5) by adopting the vision of NRC that moves from 
      traditional animal studies to the cellular pathways. Acute, subacute, and 
      developmental toxicity studies were assayed according to the Organization for 
      Economic Cooperation and Development (OECD) guidelines. The stress response 
      pathway, toxicity pathway, and adverse effects outcome parameters were analyzed 
      by using their standard protocols. The results showed that the acute toxicity 
      study increases the liver enzyme levels. In a subacute toxicity study, alkaline 
      phosphatase (ALP) levels were raised in both male and female animals. SF5 
      significantly increases the normal sperm count in the male animals corresponding 
      to a decrease in the abnormality count. Developmental toxicity showed the normal 
      skeletal and morphological parameters, except little hydrocephalus was observed 
      in developmental toxicity. Doses of 20 mg/kg in males and 4 mg/kg in females 
      showed decreased glutathione (GSH) levels in the kidney and liver. MDA levels 
      were also increased in the kidney and liver. However, histopathological studies 
      did not show any cellular change in these organs. No statistical difference was 
      observed in histamine levels, testosterone, nuclear factor erythroid two-related 
      factor-2 (Nrf2), and nuclear factor-kappa B (NF-kappaB), which showed no initiation 
      of the stress response, toxicity, and adverse effect pathways. Immunomodulation 
      was observed at low doses in subacute toxicity studies. It was concluded that SF5 
      did not produce abrupt and high-toxicity levels in organs and biochemical 
      parameters. So, it is safe for further studies.
CI  - Copyright (c) 2022 Anwar, Saleem, rehman, Ahmad, Ismail, Mirza and Ahmad.
FAU - Anwar, Fareeha
AU  - Anwar F
AD  - Riphah Institute of Pharmaceutical Sciences, Riphah International University, 
      Lahore, Pakistan.
AD  - Riphah Institute of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, 
      Riphah International University, Islamabad, Pakistan.
FAU - Saleem, Uzma
AU  - Saleem U
AD  - Department of Pharmacology, Faculty of Pharmaceutical Sciences, Govt. College 
      University, Faisalabad, Pakistan.
FAU - Rehman, Atta Ur
AU  - Rehman AU
AD  - Department of Pharmacy, Forman Christian College, Lahore, Pakistan.
FAU - Ahmad, Bashir
AU  - Ahmad B
AD  - Riphah Institute of Pharmaceutical Sciences, Riphah International University, 
      Lahore, Pakistan.
AD  - Riphah Institute of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, 
      Riphah International University, Islamabad, Pakistan.
FAU - Ismail, Tariq
AU  - Ismail T
AD  - Department of Pharmacy, COMSATS Institute of Information Technology-Abbottabad 
      Campus, Abottabad, Pakistan.
FAU - Mirza, Muhammad Usman
AU  - Mirza MU
AD  - Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, 
      Canada.
FAU - Ahmad, Sarfraz
AU  - Ahmad S
AD  - Drug Design and Development Research Group (DDDRG), Department of Chemistry, 
      Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia.
LA  - eng
PT  - Journal Article
DEP - 20220120
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8811508
OTO - NOTNLM
OT  - Nrf2
OT  - SF5
OT  - acute oral toxicity
OT  - biochemical parameters
OT  - oxidative stress markers
OT  - stress response pathway
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/02/08 06:00
MHDA- 2022/02/08 06:01
PMCR- 2022/01/20
CRDT- 2022/02/07 05:29
PHST- 2021/11/07 00:00 [received]
PHST- 2021/12/20 00:00 [accepted]
PHST- 2022/02/07 05:29 [entrez]
PHST- 2022/02/08 06:00 [pubmed]
PHST- 2022/02/08 06:01 [medline]
PHST- 2022/01/20 00:00 [pmc-release]
AID - 810704 [pii]
AID - 10.3389/fphar.2021.810704 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Jan 20;12:810704. doi: 10.3389/fphar.2021.810704. 
      eCollection 2021.