Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease
The presented study was designed to probe the toxicity potential of newly identified compound naphthalen-2-yl 3,5-dinitrobenzoate (SF1). Acute, subacute toxicity and teratogenicity studies were performed as per Organization of economic cooperation and development (OECD) 425, 407, and 414 test guidel...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-05-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.607026/full |
| _version_ | 1818961431810277376 |
|---|---|
| author | Fareeha Anwar Fareeha Anwar Uzma Saleem Atta-Ur Rehman Bashir Ahmad Matheus Froeyen Muhammad Usman Mirza Lee Yean Kee Iskandar Abdullah Sarfraz Ahmad |
| author_facet | Fareeha Anwar Fareeha Anwar Uzma Saleem Atta-Ur Rehman Bashir Ahmad Matheus Froeyen Muhammad Usman Mirza Lee Yean Kee Iskandar Abdullah Sarfraz Ahmad |
| author_sort | Fareeha Anwar |
| collection | DOAJ |
| description | The presented study was designed to probe the toxicity potential of newly identified compound naphthalen-2-yl 3,5-dinitrobenzoate (SF1). Acute, subacute toxicity and teratogenicity studies were performed as per Organization of economic cooperation and development (OECD) 425, 407, and 414 test guidelines, respectively. An oral dose of 2000 mg/kg to rats for acute toxicity. Furthermore, 5, 10, 20, and 40 mg/kg doses were administered once daily for 28 days in subacute toxicity study. Teratogenicity study was performed with 40 mg/kg due to its excellent anti-Alzheimer results at this dose. SF1 induced a significant rise in Alkaline Phosphatases (ALP), bilirubin, white blood cells (WBC), and lymphocyte levels with a decrease in platelet count. Furthermore, the reduction in urea, uric acid, and aspartate transaminase (AST) levels and an increase in total protein levels were measured in subacute toxicity. SF1 increased spermatogenesis at 5 and 10 mg/kg doses. Teratogenicity study depicted no resorptions, early abortions, cleft palate, spina bifida and any skeletal abnormalities in the fetuses. Oxidative stress markers (Superoxide dismutase (SOD), Catalase (CAT), and glutathione (GSH) were increased in all the experiments, whereas the effect on melanoaldehyde Malondialdehyde (MDA) levels was variable. Histopathology further corroborated these results with no change in the architectures of selected organs. Consequently, a 2000 mg/kg dose of SF1 tends to induce minor liver dysfunction along with immunomodulation, and it is well below its LD50. Moreover, it can be safely used in pregnancy owing to its no detectable teratogenicity. |
| first_indexed | 2024-12-20T12:13:06Z |
| format | Article |
| id | doaj.art-aa38a13278484fff8aef7aea148cd067 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T12:13:06Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-aa38a13278484fff8aef7aea148cd0672022-12-21T19:41:12ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-05-011210.3389/fphar.2021.607026607026Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer DiseaseFareeha Anwar0Fareeha Anwar1Uzma Saleem2Atta-Ur Rehman3Bashir Ahmad4Matheus Froeyen5Muhammad Usman Mirza6Lee Yean Kee7Iskandar Abdullah8Sarfraz Ahmad9Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, PakistanRiphah Faculty of Pharmaceutical Sciences, Riphah International University, Islamabad, PakistanDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Govt. College University, Faisalabad, PakistanDepartment of Pharmacy, Forman Christian University, Lahore, PakistanRiphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, PakistanDepartment of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, Medicinal Chemistry, University of Leuven, Leuven, BelgiumDepartment of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, Medicinal Chemistry, University of Leuven, Leuven, BelgiumDepartment of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur, MalaysiaDepartment of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur, MalaysiaDepartment of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur, MalaysiaThe presented study was designed to probe the toxicity potential of newly identified compound naphthalen-2-yl 3,5-dinitrobenzoate (SF1). Acute, subacute toxicity and teratogenicity studies were performed as per Organization of economic cooperation and development (OECD) 425, 407, and 414 test guidelines, respectively. An oral dose of 2000 mg/kg to rats for acute toxicity. Furthermore, 5, 10, 20, and 40 mg/kg doses were administered once daily for 28 days in subacute toxicity study. Teratogenicity study was performed with 40 mg/kg due to its excellent anti-Alzheimer results at this dose. SF1 induced a significant rise in Alkaline Phosphatases (ALP), bilirubin, white blood cells (WBC), and lymphocyte levels with a decrease in platelet count. Furthermore, the reduction in urea, uric acid, and aspartate transaminase (AST) levels and an increase in total protein levels were measured in subacute toxicity. SF1 increased spermatogenesis at 5 and 10 mg/kg doses. Teratogenicity study depicted no resorptions, early abortions, cleft palate, spina bifida and any skeletal abnormalities in the fetuses. Oxidative stress markers (Superoxide dismutase (SOD), Catalase (CAT), and glutathione (GSH) were increased in all the experiments, whereas the effect on melanoaldehyde Malondialdehyde (MDA) levels was variable. Histopathology further corroborated these results with no change in the architectures of selected organs. Consequently, a 2000 mg/kg dose of SF1 tends to induce minor liver dysfunction along with immunomodulation, and it is well below its LD50. Moreover, it can be safely used in pregnancy owing to its no detectable teratogenicity.https://www.frontiersin.org/articles/10.3389/fphar.2021.607026/fullacute oral toxicitysubacute toxicityteratogenicityoxidative stress markersbiochemical parameters |
| spellingShingle | Fareeha Anwar Fareeha Anwar Uzma Saleem Atta-Ur Rehman Bashir Ahmad Matheus Froeyen Muhammad Usman Mirza Lee Yean Kee Iskandar Abdullah Sarfraz Ahmad Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease Frontiers in Pharmacology acute oral toxicity subacute toxicity teratogenicity oxidative stress markers biochemical parameters |
| title | Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease |
| title_full | Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease |
| title_fullStr | Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease |
| title_full_unstemmed | Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease |
| title_short | Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease |
| title_sort | toxicity evaluation of the naphthalen 2 yl 3 5 dinitrobenzoate a drug candidate for alzheimer disease |
| topic | acute oral toxicity subacute toxicity teratogenicity oxidative stress markers biochemical parameters |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.607026/full |
| work_keys_str_mv | AT fareehaanwar toxicityevaluationofthenaphthalen2yl35dinitrobenzoateadrugcandidateforalzheimerdisease AT fareehaanwar toxicityevaluationofthenaphthalen2yl35dinitrobenzoateadrugcandidateforalzheimerdisease AT uzmasaleem toxicityevaluationofthenaphthalen2yl35dinitrobenzoateadrugcandidateforalzheimerdisease AT attaurrehman toxicityevaluationofthenaphthalen2yl35dinitrobenzoateadrugcandidateforalzheimerdisease AT bashirahmad toxicityevaluationofthenaphthalen2yl35dinitrobenzoateadrugcandidateforalzheimerdisease AT matheusfroeyen toxicityevaluationofthenaphthalen2yl35dinitrobenzoateadrugcandidateforalzheimerdisease AT muhammadusmanmirza toxicityevaluationofthenaphthalen2yl35dinitrobenzoateadrugcandidateforalzheimerdisease AT leeyeankee toxicityevaluationofthenaphthalen2yl35dinitrobenzoateadrugcandidateforalzheimerdisease AT iskandarabdullah toxicityevaluationofthenaphthalen2yl35dinitrobenzoateadrugcandidateforalzheimerdisease AT sarfrazahmad toxicityevaluationofthenaphthalen2yl35dinitrobenzoateadrugcandidateforalzheimerdisease |