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Expression data from mouse liver tissue treated by PM2.5 and metformin for two weeks.

ABSTRACT: There is a lot of epidemiological evidence that PM2.5 causes liver disease, and metformin can alleviate these diseases.However, the precise mechanism remains unclear.Our study defined the dynamic changes of the differentially expressed genes related PM2.5 induced diseases, and provide basis for comprehensive understanding of the mechanism at the transcriptome level. We investigated PM2.5 induced gene expression alteration associated with the development of liver injury by microarray in a ob/ob mouse model.

ORGANISM(S): Mus musculus

PROVIDER: GSE186900 | GEO | 2021/11/03

REPOSITORIES: GEO

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Project description:In a subacute study, male Wistar rats were treated daily by gavage with 800 mg/kg metformin for 1, 3, or 14 consecutive days, followed by necropsy 24h after the last application. The biguanide metformin is a widely used antidiabetic drug, which has received great interest in oncology research in recent years after an epidemiological study showed a link between metformin treatment and a reduced cancer risk in diabetic patients. Since mitochondrial metabolism has become a target for possible cancer therapeutic approaches, especially for tumors relying on oxidative metabolism, mitochondrial complex I inhibition is under discussion to be responsible for the anti-cancer effect of metformin. The known strong complex I inhibitor Rotenone has also shown anti-cancer activity, however is associated with toxic effects. Therefore, we compared metformin and phenformin, another biguanide withdrawn from the marked as antidiabetic due to safety reasons, with rotenone, to elucidate potential mechanisms rendering biguanides apparently less toxic than rotenone. In this context, various blood and tissue parameters as well as histopathology were measured and/or evaluated. Moreover, gene expression profiling was conducted in liver and heart due to the high metabolic activity and high energy demand. All investigations were based on an experimental design previously described for mechanistic investigations of the effects of rotenone. Our examinations regarding gene expression showed that 1630 transcripts were deregulated by rotenone, metformin and/or phenformin in liver, whereas 777 transcripts were deregulated in heart, indicating that the heart is less affected by these compounds. Overall, the mechanistic profile of phenformin appears to be similar to that of rotenone, yet at a quantitatively reduced level, whereas metformin displayed only transient similarities after one day of treatment. These differences are likely due to differential molecular properties of these compounds, especially concerning their effects on mitochondria: Metformin, in contrast to rotenone, requires a certain mitochondrial potential to allow accumulation in this organelle, thereby self-limiting its entry and thus ability to inhibit mitochondrial function, whereas rotenone and to some extent also phenformin can enter mitochondria freely. Thus, our more detailed molecular characterization of these compounds suggests that inhibition of mitochondrial functions can serve as target for an anti-cancer mode of action, yet should be self-limited or balanced to some extent to avoid exhaustion of all energy stores.

Dataset Information

Expression data from mouse liver tissue treated by PM2.5 and metformin for two weeks.

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