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Protective effect of morin by targeting mitochondrial reactive oxygen species induced by hydrogen peroxide demonstrated at a molecular level in MDCK epithelial cells

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Abstract

Background

The development of diabetic nephropathy is aided by the presence of oxidative stress. Morin, a natural flavonoid molecule, has been shown to have antioxidant and anti-diabetic properties. However, little is known about the mechanism of its protective effect in diabetic nephropathy pathogenesis caused by oxidative stress.

Methods

Using Madin-Darby canine kidney (MDCK) cells as a working model, the current study investigates the detailed mechanism of morin's beneficial action. In hydrogen peroxide-induced oxidative stressed MDCK cells, there was a considerable rise in intracellular ROS and decreased antioxidant enzyme levels.

Results

Morin has a higher binding affinity for the antioxidant receptor; according to in silico study using molecular docking and ADMET, it is predicted to be an orally active molecule. While morin administration increased SOD and CAT activity in oxidative stress-induced MDCK cells, it also reduced mitochondrial oxidative stress and apoptosis. Furthermore, the present study discovered the molecular mechanism through which morin reduced oxidative stress in MDCK cells by upregulating antioxidant enzyme molecules including GST, GPx, and GCS.

Conclusion

These findings suggest that morin reduces H2O2-induced oxidative stress, reduces DNA oxidative damage, and prevents the depletion of antioxidant genes in MDCK cells.

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Abbreviations

MDCK:

Madin-Darby canine kidney

ROS:

Reactive oxygen species

H2O2 :

Hydrogen peroxide

DMSO:

Dimethyl sulphoxide

LDH:

Lactate dehydrogenase

ANOVA :

One-way analysis of variance

HBDs:

Hydrogen-bond donors

HBAs:

Hydrogen-bond acceptors

TPSA:

Total polar surface area

ADMET:

Absorption, distribution, metabolism, excretion, and toxicity

GI:

Gastrointestinal

BBB:

Blood–brain barrier

CYPs:

Cytochromes

GCS:

Glutamyl-cysteine synthetase

GST:

Glutathione-S-transferase

GPx:

Glutathione peroxidase

DCFDA:

Dichlorodihydrofluorescein diacetate

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PKI, MV, AG, GS, PR, JA conceived the study. PR provided the Morin. PKI, MV, AG, GS performed the experiments. PR, JA provided the reagents for the study. All authors designed the experiments, analysed the data, wrote the manuscript, read and approved the final version of the manuscript.

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Correspondence to Jesu Arockiaraj.

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Issac, P.K., Velayutham, M., Guru, A. et al. Protective effect of morin by targeting mitochondrial reactive oxygen species induced by hydrogen peroxide demonstrated at a molecular level in MDCK epithelial cells. Mol Biol Rep 49, 4269–4279 (2022). https://doi.org/10.1007/s11033-022-07261-z

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