Genotoxic and Mutagenic Potential of Anti-Diabetic Drugs (Sitagliptin and Metformin) Alone And In Combination With Artificial Sweeteners.
By: Komal Najam
| Prof. Dr. Muhammad Ashraf.
Contributor(s): Dr. Imran Altaf | Dr. Muhammad Adil Rasheed.
Material type: 
BookPublisher: 2013Subject(s): Department of Pharmaoclogy & ToxicologyDDC classification: 1799,T Dissertation note: Metformin most commonly prescribed oral anti hyperglycemic drug for type 2 diabetes whereas Sitagliptin recently approved oral antidabetic drug for type 2 diabetes were evaluated for their mutagenic and genotoxic potential alone and in combination with three artificial sweeteners (Saccharin, Aspartame and Acesulfame-K) normally consumed by diabetic individuals.
In this research project Ames Salmonella/microsome assay was performed to check the mutagenicity of Metformin and Sitagliptin alone and in combination with artificial sweeteners using mutant Salmonella tester strains TA100 and TA98 with and without the S9 whereas Genotoxicity was evaluated by Single Cell Gel Alkaline Electrophoresis/Comet.
The results indicated that Metformin alone showed mutagenic effect at 120µg/plate against TA100 with S9mix. However Metformin when tested in combination with artificial sweeteners, significant enhance in mutagenicity occurred only against TA100 with and without S9. Sitagliptin displayed mutagenic potential only to TA98 with S9mix at the concentration of 3040µg/plate. In addition significant enhance in mutagenicity occurred when tested in combination with artificial sweeteners against both strains with and without S9. In case of genotoxicity both Metformin and Sitagliptin results indicated significant increase in DNA damage in dose dependant manner as compared to negative control. Though Metformin and Sitagliptin in combination with artificial sweetener did not reveal any significant boost in the genotoxicity relative to when they were tested alone.
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Thesis
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UVAS Library Thesis Section | Veterinary Science | 1799,T (Browse shelf) | Available | 1799,T |
Metformin most commonly prescribed oral anti hyperglycemic drug for type 2 diabetes whereas Sitagliptin recently approved oral antidabetic drug for type 2 diabetes were evaluated for their mutagenic and genotoxic potential alone and in combination with three artificial sweeteners (Saccharin, Aspartame and Acesulfame-K) normally consumed by diabetic individuals.
In this research project Ames Salmonella/microsome assay was performed to check the mutagenicity of Metformin and Sitagliptin alone and in combination with artificial sweeteners using mutant Salmonella tester strains TA100 and TA98 with and without the S9 whereas Genotoxicity was evaluated by Single Cell Gel Alkaline Electrophoresis/Comet.
The results indicated that Metformin alone showed mutagenic effect at 120µg/plate against TA100 with S9mix. However Metformin when tested in combination with artificial sweeteners, significant enhance in mutagenicity occurred only against TA100 with and without S9. Sitagliptin displayed mutagenic potential only to TA98 with S9mix at the concentration of 3040µg/plate. In addition significant enhance in mutagenicity occurred when tested in combination with artificial sweeteners against both strains with and without S9. In case of genotoxicity both Metformin and Sitagliptin results indicated significant increase in DNA damage in dose dependant manner as compared to negative control. Though Metformin and Sitagliptin in combination with artificial sweetener did not reveal any significant boost in the genotoxicity relative to when they were tested alone.
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