Toxicity evaluation induced by single and 28-days repeated exposure of withametelin and daturaolone in Sprague Dawley rats
Safe preclinical dose determination is predictive of human toxicity and can have a profound impact on the overall progress of the compound in early drug discovery process. In this respect, current study sought to investigate for the first time the acute and subacute oral toxicity of two pharmacologi...
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| Format: | Article |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.999078/full |
| _version_ | 1798001258580148224 |
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| author | Muhammad Waleed Baig Muhammad Majid Bakht Nasir Bakht Nasir Syed Shams ul Hassan Syed Shams ul Hassan Simona Bungau Ihsan-ul Haq |
| author_facet | Muhammad Waleed Baig Muhammad Majid Bakht Nasir Bakht Nasir Syed Shams ul Hassan Syed Shams ul Hassan Simona Bungau Ihsan-ul Haq |
| author_sort | Muhammad Waleed Baig |
| collection | DOAJ |
| description | Safe preclinical dose determination is predictive of human toxicity and can have a profound impact on the overall progress of the compound in early drug discovery process. In this respect, current study sought to investigate for the first time the acute and subacute oral toxicity of two pharmacologically active natural compounds i.e., withametelin and daturaolone in Sprague Dawley rats following OECD guideline 420 and 407, respectively. As per acute toxicity studies, withametelin and daturaolone were characterized as Globally Harmonized System (GHS) category 4 and 5 compounds, respectively. Sub-acute daily dose of withametelin was 5, 2.5, and 1.25 mg/kg but, for daturaolone, it was 10, 5, and 2.5 mg/kg. High dose (5 and 2.5 mg/kg) withametelin groups showed dose dependent changes in the general, hematological, biochemical and histopathological parameters in both sexes, the most prominent being hyperthyroidism while no toxicity was observed at lower doses (1.25 and 0.75 mg/kg), No Observable Adverse Effect Level (NOAEL) being 1.25 mg/kg. Daturaolone was comparatively safer and showed dose dependent significant changes in hepatic enzyme (Alanine Transaminase), bilirubin, creatinine, and glucose levels while histological changes in testes were also observed. Lower doses (5, 2.5, and 1.25 mg/kg) of daturaolone showed no significant toxic effects and 5 mg/kg was declared as its NOAEL. Depending upon our findings, starting effective oral dose levels of 1.25 mg/kg/day for withametelin and 5 mg/kg/day for daturaolone are proposed for repeated dose (up to 28 days) preclinical pharmacological evaluation models. Long term studies with more behavioral, biochemical, histopathological and hormonal parameters are proposed to strengthen the findings. |
| first_indexed | 2024-04-11T11:33:25Z |
| format | Article |
| id | doaj.art-4997b0482ad745d2931fdabafaad2947 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T11:33:25Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-4997b0482ad745d2931fdabafaad29472022-12-22T04:26:03ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.999078999078Toxicity evaluation induced by single and 28-days repeated exposure of withametelin and daturaolone in Sprague Dawley ratsMuhammad Waleed Baig0Muhammad Majid1Bakht Nasir2Bakht Nasir3Syed Shams ul Hassan4Syed Shams ul Hassan5Simona Bungau6Ihsan-ul Haq7Department of Pharmacy, Quaid-i-Azam University, Islamabad, PakistanFaculty of Pharmacy, Capital University of Science and Technology, Islamabad, PakistanDepartment of Pharmacy, Quaid-i-Azam University, Islamabad, PakistanCharles Institute of Dermatology, School of Medicine, University College Dublin, Dublin, IrelandShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Natural Product Chemistry, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, RomaniaDepartment of Pharmacy, Quaid-i-Azam University, Islamabad, PakistanSafe preclinical dose determination is predictive of human toxicity and can have a profound impact on the overall progress of the compound in early drug discovery process. In this respect, current study sought to investigate for the first time the acute and subacute oral toxicity of two pharmacologically active natural compounds i.e., withametelin and daturaolone in Sprague Dawley rats following OECD guideline 420 and 407, respectively. As per acute toxicity studies, withametelin and daturaolone were characterized as Globally Harmonized System (GHS) category 4 and 5 compounds, respectively. Sub-acute daily dose of withametelin was 5, 2.5, and 1.25 mg/kg but, for daturaolone, it was 10, 5, and 2.5 mg/kg. High dose (5 and 2.5 mg/kg) withametelin groups showed dose dependent changes in the general, hematological, biochemical and histopathological parameters in both sexes, the most prominent being hyperthyroidism while no toxicity was observed at lower doses (1.25 and 0.75 mg/kg), No Observable Adverse Effect Level (NOAEL) being 1.25 mg/kg. Daturaolone was comparatively safer and showed dose dependent significant changes in hepatic enzyme (Alanine Transaminase), bilirubin, creatinine, and glucose levels while histological changes in testes were also observed. Lower doses (5, 2.5, and 1.25 mg/kg) of daturaolone showed no significant toxic effects and 5 mg/kg was declared as its NOAEL. Depending upon our findings, starting effective oral dose levels of 1.25 mg/kg/day for withametelin and 5 mg/kg/day for daturaolone are proposed for repeated dose (up to 28 days) preclinical pharmacological evaluation models. Long term studies with more behavioral, biochemical, histopathological and hormonal parameters are proposed to strengthen the findings.https://www.frontiersin.org/articles/10.3389/fphar.2022.999078/fullwithametelindaturaolonetoxicityin vivoDatura |
| spellingShingle | Muhammad Waleed Baig Muhammad Majid Bakht Nasir Bakht Nasir Syed Shams ul Hassan Syed Shams ul Hassan Simona Bungau Ihsan-ul Haq Toxicity evaluation induced by single and 28-days repeated exposure of withametelin and daturaolone in Sprague Dawley rats Frontiers in Pharmacology withametelin daturaolone toxicity in vivo Datura |
| title | Toxicity evaluation induced by single and 28-days repeated exposure of withametelin and daturaolone in Sprague Dawley rats |
| title_full | Toxicity evaluation induced by single and 28-days repeated exposure of withametelin and daturaolone in Sprague Dawley rats |
| title_fullStr | Toxicity evaluation induced by single and 28-days repeated exposure of withametelin and daturaolone in Sprague Dawley rats |
| title_full_unstemmed | Toxicity evaluation induced by single and 28-days repeated exposure of withametelin and daturaolone in Sprague Dawley rats |
| title_short | Toxicity evaluation induced by single and 28-days repeated exposure of withametelin and daturaolone in Sprague Dawley rats |
| title_sort | toxicity evaluation induced by single and 28 days repeated exposure of withametelin and daturaolone in sprague dawley rats |
| topic | withametelin daturaolone toxicity in vivo Datura |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.999078/full |
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