Volume 30, Issue 1 (March 2026)
Physiol Pharmacol 2026, 30(1): 110-124 |
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Abnosi M H, Parvaz M. Gallic acid mitigates DEHP-Induced oxidative stress
by upregulating the Nrf2-NFkB pathway in rat bone
marrow mesenchymal stem cells. Physiol Pharmacol 2026; 30 (1) :110-124
URL: http://ppj.phypha.ir/article-1-2478-en.html
URL: http://ppj.phypha.ir/article-1-2478-en.html
Abstract: (1368 Views)
Introduction: Di-2-ethylhexyl phthalate (DEHP), a chemical used in medical bags and tubing, can leach into the bloodstream and bone marrow, causing oxidative stress in bone marrow mesenchymal stem cells (BMSCs). This study investigates the potential of gallic acid (GA), a potent antioxidant, to counteract DEHP-induced oxidative effects in vitro.
Methods: BMSCs were exposed to various GA concentrations (0.063, 0.125, 0.25, 1, and 10 μM) for 4 days, identifying 0.25 μM GA as the optimal concentration based on cell viability. Cells were then treated with 100 and 500 μM DEHP, with or without 0.25 μM GA, for 4 or 8 days to assess viability, population doubling number, total protein levels, malondialdehyde levels, total antioxidant capacity, catalase and superoxide dismutase activity, cellular morphology, and expression of Nrf2 and NFκB genes.
Results: Treatment with DEHP led to a significant, dose- and time-dependent reduction in viability, proliferation rate, total protein levels, total antioxidant capacity, and the activity of antioxidant enzymes. In contrast, GA treatment significantly increased these parameters. Additionally, DEHP resulted in an increase in malondialdehyde levels and caused morphological changes as well as down-regulated NFκB and up-regulating Nrf2 expression. In the co-treatment group, GA counteracted the toxic effects of DEHP at 100 μM compared with control, whereas it only partially mitigated the toxic effects at 500 μM.
Conclusion: Consuming low concentrations of GA over time may reduce DEHP-induced oxidative stress. Further animal studies with GA-rich foods are essential to confirm its preventive benefits in vivo.
Methods: BMSCs were exposed to various GA concentrations (0.063, 0.125, 0.25, 1, and 10 μM) for 4 days, identifying 0.25 μM GA as the optimal concentration based on cell viability. Cells were then treated with 100 and 500 μM DEHP, with or without 0.25 μM GA, for 4 or 8 days to assess viability, population doubling number, total protein levels, malondialdehyde levels, total antioxidant capacity, catalase and superoxide dismutase activity, cellular morphology, and expression of Nrf2 and NFκB genes.
Results: Treatment with DEHP led to a significant, dose- and time-dependent reduction in viability, proliferation rate, total protein levels, total antioxidant capacity, and the activity of antioxidant enzymes. In contrast, GA treatment significantly increased these parameters. Additionally, DEHP resulted in an increase in malondialdehyde levels and caused morphological changes as well as down-regulated NFκB and up-regulating Nrf2 expression. In the co-treatment group, GA counteracted the toxic effects of DEHP at 100 μM compared with control, whereas it only partially mitigated the toxic effects at 500 μM.
Conclusion: Consuming low concentrations of GA over time may reduce DEHP-induced oxidative stress. Further animal studies with GA-rich foods are essential to confirm its preventive benefits in vivo.
Keywords: Gallic acid, Di-2-ethylhexylphthalate, Bone marrow, mesenchymal stem cells, Oxidative stress.
Type of Manuscript: Experimental research article |
Subject:
Toxicology
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