Genotoxicity evaluation of metformin and glimepiride by micronucleus assay in exfoliated urothelial cells of type 2 diabetes mellitus patients

Harishankar, M.; Logeshwaran, S.; Sujeevan, Sinnatamby; ArulJothi, K.N.; Dannie, M.A.; Devi, Arikketh

doi:10.1016/j.fct.2015.06.013

Cited by 20 publications

(8 citation statements)

References 33 publications

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“…38 However, recently it was reported that Metformin and Glimepiride increased the frequency of micronucleated cells. 39 The presence of genotoxicity in drugs currently employed to treat DM is evident; in contrast, our results show that DOAcK are not aneuploid or clastogenic agent. The OECD-423 test was conducted to evaluate the acute toxicity of DOAcK at the initial dose of 2,000 mg/kg.…”

Section: Oxidative Stress (Os) Produced By Cellular Respiration and Econtrasting

confidence: 81%

Antidiabetic effect, antioxidant activity, and toxicity of 3′,4′-Di-O-acetyl-cis-khellactone in Streptozotocin-induced diabetic rats

Domínguez-Mendoza

Cornejo-Garrido

Burgueño‐Tapia

et al. 2016

Bioorganic & Medicinal Chemistry Letters

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Section: Oxidative Stress (Os) Produced By Cellular Respiration and Econtrasting

confidence: 81%

Antidiabetic effect, antioxidant activity, and toxicity of 3′,4′-Di-O-acetyl-cis-khellactone in Streptozotocin-induced diabetic rats

Domínguez-Mendoza

Cornejo-Garrido

Burgueño‐Tapia

et al. 2016

Bioorganic & Medicinal Chemistry Letters

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“…In contrast, Grindel et al argued that most studies compare DNA damage of DM2 patients to healthy controls but disregard the fact that, within its progression, DM2 is a considerably diverse disease requesting different medical treatment approaches leading to a broad range of hyperglycemia levels [ 30 ]. Some reports have argued that metformin, commonly prescribed for DM2 [ 39 ], could have genotoxic potential either alone or in combination with other therapeutics [ 2 , 40 ]. In contrast, there are studies showing that short-term exposure to metformin does not increase micronuclei in human cells [ 41 , 42 ].…”

Section: Resultsmentioning

confidence: 99%

Increased Micronuclei Frequency in Oral and Lingual Epithelium of Treated Diabetes Mellitus Patients

Ojeda

Aguilar‐Medina

Olimón-Andalón

et al. 2018

BioMed Research International

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Diabetes mellitus (DM) is a metabolic disease characterized by persistent high levels of glucose in plasma. Chronic hyperglycemia is thought to increase oxidative stress and the formation of free radicals that in turn damage cells. Thus, we decided to determine the frequency of nuclear abnormalities in epithelial cells from cheek and tongue mucosa of DM patients with type 1 (DM1, treated only with insulin) and type 2 (DM2, treated with metformin) using the buccal micronucleus cytome (BMCyt) assay. Micronuclei frequency in cheek epithelial cells was higher in both DM1 (0.75 ± 0.31, P < 0.001) and DM2 (0.52 ± 0.27, P < 0.001) patients, as compared to healthy controls (0.07 ± 0.06). Similarly, micronuclei frequency in tongue epithelium was increased in DM1 (0.81 ± 0.22, P < 0.001) and DM2 (0.41 ± 0.21, P < 0.001) groups, in comparison to controls (0.06 ± 0.05). Besides, we found a positive correlation between micronuclei frequency and the onset time of DM2 in both cheek (ρ = 0.69, P < 0.001) and tongue epithelial cells (ρ = 0.71, P < 0.001), but not with onset time of DM1 or age of the patients. Considering all this, we pose that BMCyt could serve as a fast and easily accessible test to assess genotoxic damage during dental visits of DM patients, helping to monitor their disease.

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“…In recent years, it has been suggested that antidiabetic drugs can cause cancer (Cordero et al 2009;Giovannucci et al 2010;Matteucci and Giampietro 2011). Since the incidence of cancer is higher in diabetic patients compared to the healthy population, these drugs have become subjects of genotoxicity and cytotoxicity researches (Oz Gul et al 2013;Engu ¨zel 2015;Harishankar et al 2015).…”

Section: Discussionmentioning

confidence: 99%

In vitro cytogenetic assessment and comparison of vildagliptin and sitagliptin

et al. 2019

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Vildagliptin and sitagliptin are commonly used antidiabetic drugs. Chromosomal aberration (CA), sister chromatid exchange (SCE) and cytokinesis-block micronucleus (CBMN) assays were employed to assess and compare cytotoxic and genotoxic effects of these drugs. Peripheral lymphocytes were exposed to 125 lg/ml, 250 lg/ml and 500 lg/ml of vildagliptin and 250 lg/ml, 500 lg/ml and 1000 lg/ml of sitagliptin for 24 h and 48 h with and without exogenous metabolic activation. At the end of the study, it was determined that these drugs and their metabolites had no genotoxic effects on CA, SCE and CBMN. On the other hand, parallel to the increase in dose, vildagliptin showed weak cytotoxicity on the mitotic index, and depending on its increase in dose; sitagliptin caused potential cytotoxicity and cytostatic effect on the mitotic index, nuclear division index and proliferation index. Due to their cytotoxic and cytostatic potential, these drugs inhibit cell proliferation.

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Genotoxicity evaluation of metformin and glimepiride by micronucleus assay in exfoliated urothelial cells of type 2 diabetes mellitus patients

Cited by 20 publications

References 33 publications

Antidiabetic effect, antioxidant activity, and toxicity of 3′,4′-Di-O-acetyl-cis-khellactone in Streptozotocin-induced diabetic rats

Antidiabetic effect, antioxidant activity, and toxicity of 3′,4′-Di-O-acetyl-cis-khellactone in Streptozotocin-induced diabetic rats

Increased Micronuclei Frequency in Oral and Lingual Epithelium of Treated Diabetes Mellitus Patients

In vitro cytogenetic assessment and comparison of vildagliptin and sitagliptin

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