Modulatory and Toxicological Perspectives on the Effects of the Small Molecule Kinetin
Plant hormones are small regulatory molecules that exert pharmacological actions in mammalian cells such as anti-oxidative and pro-metabolic effects. Kinetin belongs to the group of plant hormones cytokinin and has been associated with modulatory functions in mammalian cells. The mammalian adenosine...
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MDPI AG
2021-01-01
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| author | Eman M. Othman Moustafa Fathy Amany Abdlrehim Bekhit Abdel-Razik H. Abdel-Razik Arshad Jamal Yousef Nazzal Shabana Shams Thomas Dandekar Muhammad Naseem |
| author_facet | Eman M. Othman Moustafa Fathy Amany Abdlrehim Bekhit Abdel-Razik H. Abdel-Razik Arshad Jamal Yousef Nazzal Shabana Shams Thomas Dandekar Muhammad Naseem |
| author_sort | Eman M. Othman |
| collection | DOAJ |
| description | Plant hormones are small regulatory molecules that exert pharmacological actions in mammalian cells such as anti-oxidative and pro-metabolic effects. Kinetin belongs to the group of plant hormones cytokinin and has been associated with modulatory functions in mammalian cells. The mammalian adenosine receptor (A2a-R) is known to modulate multiple physiological responses in animal cells. Here, we describe that kinetin binds to the adenosine receptor (A2a-R) through the Asn253 residue in an adenosine dependent manner. To harness the beneficial effects of kinetin for future human use, we assess its acute toxicity by analyzing different biochemical and histological markers in rats. Kinetin at a dose below 1 mg/kg had no adverse effects on the serum level of glucose or on the activity of serum alanine transaminase (ALT) or aspartate aminotransferase (AST) enzymes in the kinetin treated rats. Whereas, creatinine levels increased after a kinetin treatment at a dose of 0.5 mg/kg. Furthermore, 5 mg/kg treated kinetin rats showed normal renal corpuscles, but a mild degeneration was observed in the renal glomeruli and renal tubules, as well as few degenerated hepatocytes were also observed in the liver. Kinetin doses below 5 mg/kg did not show any localized toxicity in the liver and kidney tissues. In addition to unraveling the binding interaction between kinetin and A2a-R, our findings suggest safe dose limits for the future use of kinetin as a therapeutic and modulatory agent against various pathophysiological conditions. |
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| publishDate | 2021-01-01 |
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| series | Molecules |
| spelling | doaj.art-596795f64e4f42dab272afe21aaf62a42023-12-03T15:00:04ZengMDPI AGMolecules1420-30492021-01-0126367010.3390/molecules26030670Modulatory and Toxicological Perspectives on the Effects of the Small Molecule KinetinEman M. Othman0Moustafa Fathy1Amany Abdlrehim Bekhit2Abdel-Razik H. Abdel-Razik3Arshad Jamal4Yousef Nazzal5Shabana Shams6Thomas Dandekar7Muhammad Naseem8Department of Biochemistry, Faculty of Pharmacy, University of Minia, Minia 61519, EgyptDepartment of Biochemistry, Faculty of Pharmacy, University of Minia, Minia 61519, EgyptDepartment of Biochemistry, Faculty of Pharmacy, University of Minia, Minia 61519, EgyptDepartment of Histology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef 62511, EgyptDepartment of Biology, College of Science, University of Ha’il, Ha’il 2240, Saudi ArabiaDepartment of Life and Environmental Sciences, College of Natural and Health Sciences, Zayed University, Abu Dhabi 144534, UAEDepartment of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, PakistanDepartment of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, GermanyDepartment of Life and Environmental Sciences, College of Natural and Health Sciences, Zayed University, Abu Dhabi 144534, UAEPlant hormones are small regulatory molecules that exert pharmacological actions in mammalian cells such as anti-oxidative and pro-metabolic effects. Kinetin belongs to the group of plant hormones cytokinin and has been associated with modulatory functions in mammalian cells. The mammalian adenosine receptor (A2a-R) is known to modulate multiple physiological responses in animal cells. Here, we describe that kinetin binds to the adenosine receptor (A2a-R) through the Asn253 residue in an adenosine dependent manner. To harness the beneficial effects of kinetin for future human use, we assess its acute toxicity by analyzing different biochemical and histological markers in rats. Kinetin at a dose below 1 mg/kg had no adverse effects on the serum level of glucose or on the activity of serum alanine transaminase (ALT) or aspartate aminotransferase (AST) enzymes in the kinetin treated rats. Whereas, creatinine levels increased after a kinetin treatment at a dose of 0.5 mg/kg. Furthermore, 5 mg/kg treated kinetin rats showed normal renal corpuscles, but a mild degeneration was observed in the renal glomeruli and renal tubules, as well as few degenerated hepatocytes were also observed in the liver. Kinetin doses below 5 mg/kg did not show any localized toxicity in the liver and kidney tissues. In addition to unraveling the binding interaction between kinetin and A2a-R, our findings suggest safe dose limits for the future use of kinetin as a therapeutic and modulatory agent against various pathophysiological conditions.https://www.mdpi.com/1420-3049/26/3/670cytokinin kinetinmodulatory effectsin vivo toxicityA2a-R receptor |
| spellingShingle | Eman M. Othman Moustafa Fathy Amany Abdlrehim Bekhit Abdel-Razik H. Abdel-Razik Arshad Jamal Yousef Nazzal Shabana Shams Thomas Dandekar Muhammad Naseem Modulatory and Toxicological Perspectives on the Effects of the Small Molecule Kinetin Molecules cytokinin kinetin modulatory effects in vivo toxicity A2a-R receptor |
| title | Modulatory and Toxicological Perspectives on the Effects of the Small Molecule Kinetin |
| title_full | Modulatory and Toxicological Perspectives on the Effects of the Small Molecule Kinetin |
| title_fullStr | Modulatory and Toxicological Perspectives on the Effects of the Small Molecule Kinetin |
| title_full_unstemmed | Modulatory and Toxicological Perspectives on the Effects of the Small Molecule Kinetin |
| title_short | Modulatory and Toxicological Perspectives on the Effects of the Small Molecule Kinetin |
| title_sort | modulatory and toxicological perspectives on the effects of the small molecule kinetin |
| topic | cytokinin kinetin modulatory effects in vivo toxicity A2a-R receptor |
| url | https://www.mdpi.com/1420-3049/26/3/670 |
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