Genotoxicity of antiobesity drug orlistat and effect of caffeine intervention: an <i>in vitro</i> study

Chakrabarti, Manoswini; Ghosh, Ilika; Jana, Aditi; Ghosh, Manosij; Mukherjee, Anita

doi:10.1080/01480545.2016.1236128

Cited by 12 publications

(8 citation statements)

References 24 publications

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“…Assisting with weight loss, it also lowers blood glucose levels . However, long-term use of orlistat can induce side effects, including diarrhea, increased stool frequency, oily stool, gastrointestinal flatulence, as well as other side effects, , and may also lead to acute pancreatitis . Therefore, the development of efficient, safe, and nontoxic new compounds for weight loss is important.…”

Section: Introductionmentioning

confidence: 99%

“…10 However, long-term use of orlistat can induce side effects, including diarrhea, increased stool frequency, oily stool, gastrointestinal flatulence, as well as other side effects, 11,12 and may also lead to acute pancreatitis. 13 Therefore, the development of efficient, safe, and nontoxic new compounds for weight loss is important. Natural compounds derived from plants are characterized by high bioactivity, low toxicity, and extensive resources.…”

Section: ■ Introductionmentioning

confidence: 99%

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Cerasus humilis Cherry Polyphenol Reduces High-Fat Diet-Induced Obesity in C57BL/6 Mice by Mitigating Fat Deposition, Inflammation, and Oxidation

Liu

Chang

et al. 2020

J. Agric. Food Chem.

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This study aimed to determine the anti-obesity effects and mechanisms of Cerasus humilis polyphenol (CHP) in C57BL/6 obese mice and 3T3-L1 cells. High-performance liquid chromatography−electrospray ionization-tandem mass spectrometry was used for the qualitative and quantitative identification of CHP components. The obese mice, induced by feeding high-fat diet (HFD), were treated with CHP (250 mg/kg/day) by gavage for 12 weeks. Orlistat was gavaged at 15.6 mg/kg bw/day, as a positive control group. The analysis revealed that the main components of CHP were procyanidin B2, cyanidin-3glucoside, and pelargonidin-3-glucoside. CHP dietary supplementation significantly reduced body weight and improved blood lipid measurements in HFD-fed mice (p < 0.01). Moreover, it inhibited mRNA expression of miR-122, Srebp-1c, and Cpt1a (p < 0.01) and reduced hepatic lipid deposition, as seen by hematoxylin and eosin staining. CHP downregulated the protein expression of PPARγ and C/EBPα in HFD-induced obese mice and inhibited adipocyte differentiation (p < 0.01). Compared with the HFD group, CHP supplementation had an obvious anti-inflammatory effect (decreased protein expression, such as TNF-α, IL-6, and MCP1), reducing leptin levels and TNF-α secretion in serum and cells (p < 0.01). CHP significantly inhibited the expression of miR-27a/b (53.3 and 29.9%, p < 0.01) in mice retroperitoneal white adipocytes, enhancing the expression of the target gene Prdm16 and significantly upregulating Sirt1 (105.5%, p < 0.01) compared with the HFD group. Moreover, CHP supplementation effectively improved oxidative stress (ROS, T-AOC, SOD, CAT, and GSH-Px) induced by HFD in obese mice (p < 0.01). Thus, CHP mitigates adipocyte differentiation, browning of white adipocytes, and reduction of inflammation and antioxidant activity to reduce obesity. Consequently, these results provide novel insights into the anti-obesity roles of CHP in HFD-induced obesity.

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Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Cerasus humilis Cherry Polyphenol Reduces High-Fat Diet-Induced Obesity in C57BL/6 Mice by Mitigating Fat Deposition, Inflammation, and Oxidation

Liu

Chang

et al. 2020

J. Agric. Food Chem.

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“…The IC 50 was reached at 30 to 50 times the THL combination MIC. THL genotoxicity was previously documented on lymphocytes from human peripheral blood at 250 μg/ml (Chakrabarti et al, 2017). To our knowledge, our work is the first study on the THL effect on airway epithelium Calu‐3 and A549 cell lines and THP‐1 monocyte cell line.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo local tolerability of a synergistic anti‐tuberculosis drug combination intended for pulmonary delivery

Ravon

Menchi

Lambot

et al. 2022

J of Applied Toxicology

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A drug combination, vancomycin (VAN) plus tetrahydrolipstatin (THL), has demonstrated an effective synergistic action in vitro against Mycobacterium tuberculosis (Mtb). The poor oral bioavailability of VAN and THL and the predominant tropism of Mtb infection to the lungs make their pulmonary administration very attractive. To evaluate their local tolerability, bronchial cells, alveolar cells and monocytes were exposed to concentrations around and above their minimal inhibitory concentration (MIC). The VAN had no inhibitory activity on the tested human cell lines, even at a concentration 125 times higher than its MIC, whereas the THL, alone or in combination with VAN, presented a cytostatic action. Monolayer epithelium showed no significant irreversible damage at concentrations up to 100 times the combination MIC.BALB/cAnNRj mice exposed to concentration of 50 times the combination MIC delivered endotracheally 3 times a week for 3 weeks showed no clinical signs or significant weight loss. The increase of proinflammatory biomarkers (i.e., IL-1, IL-6, TNFα and proportion of inflammatory cells) and cytotoxicity in bronchoalveolar lavage fluid (BALF) were non-significant. Lung histopathology did not show significant tissue damage. The VAN/THL combination at doses up to 50 times the combination MIC is found to be thus well tolerated by pulmonary route. This study is a promising result and encouraging further investigations of pulmonary administration of VAN/THL combination as dry powder for anti-tuberculosis treatment.

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“…Interestingly, some studies have reported that Orlistat, an antiobesty drug, induced DNA damage in human cells, which suggested that regular consumption of orlistat needs careful circumspection [ 32 ]. In contrast, flavonoids from cocoa in dark chocolate are able to significantly decrease important risk factors such as waist circumference, total cholesterol, LDL-cholesterol, and triglycerides, without causing DNA damage, even having a celluloprotective effect that could reverses the DNA damage in buccal epithelial cells, which is apparently caused by the systemic inflammation of obesity, along with the fact that flavonoids have been long recognized for their anti-inflammatory effect [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Daily Consumption of Chocolate Rich in Flavonoids Decreases Cellular Genotoxicity and Improves Biochemical Parameters of Lipid and Glucose Metabolism

et al. 2018

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In recent years, the incidence of atherosclerotic cardiovascular disease, obesity, and diabetes has increased largely worldwide. In the present work, we evaluated the genoprotective effect of the consumption of flavonoids-rich chocolate on 84 young volunteers. Biochemical indicators related to the prevention and treatment of cardiovascular risk and metabolic syndrome were also determined. A randomized, placebo-controlled, double-blind study was performed in the Autonomous University of Baja California. The treatments comprised the daily consumption of either 2 g of dark chocolate containing 70% cocoa, or 2 g of milk chocolate, for 6 months. The total amount of phenolic compounds and flavonoids was determined in both types of chocolate. Anthropometrical and Biochemical parameters were recorded prior to and after the study. The evaluation of the genotoxicity in buccal epithelial cells was performed throughout the duration of the study. Flavonoids from cocoa in dark chocolate significantly prevented DNA damage, and improved the nucleus integrity of cells. This effect could be related to the antioxidant capacity of the dark chocolate that decreased cellular stress. Biochemical parameters (total cholesterol, triglycerides, and LDL-cholesterol level in blood) and anthropometrical parameters (waist circumference) were improved after six months of daily intake of 2 g of dark chocolate with a 70% of cocoa.

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Genotoxicity of antiobesity drug orlistat and effect of caffeine intervention: an in vitro study

Abstract: Orlistat can induce DNA damage in human lymphocytes in vitro and caffeine was found to reduce orlistat-induced genotoxicity.

Cited by 12 publications

References 24 publications

Cerasus humilis Cherry Polyphenol Reduces High-Fat Diet-Induced Obesity in C57BL/6 Mice by Mitigating Fat Deposition, Inflammation, and Oxidation

Cerasus humilis Cherry Polyphenol Reduces High-Fat Diet-Induced Obesity in C57BL/6 Mice by Mitigating Fat Deposition, Inflammation, and Oxidation

In vitro and in vivo local tolerability of a synergistic anti‐tuberculosis drug combination intended for pulmonary delivery

Daily Consumption of Chocolate Rich in Flavonoids Decreases Cellular Genotoxicity and Improves Biochemical Parameters of Lipid and Glucose Metabolism

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