TABLE 2.

The metformin antioxidant properties based on animal model studies.

Model	Dose	Parameters	Results	References	Limitations
rat model of arsenic-induced diabetes	300 mg/kg	reduction in oxidative stress	SIRT3 pathway activation	Javadipour et al. (2019)	SIRT3 expression elevated parallel to other antioxidant defense component
diabetic mouse model	250 mg/kg	improvements in lipid metabolism and a reduction in oxidative stress	Increased paraoxonase activity	Roxo et al. (2019)	Uncreated metabolic memory associated with diabetes
Rat model	1 mmol/L	Reduction in oxidative stress	activation of the SIRT3 and AMPK pathways	Lai et al. (2016)	the lack of beneficial effects of nitrite and metformin in the more severely affected and older rats
Diabetic rat model	500 mg/kg metformin and L-ergothioneine	significantly increased the expression of major antioxidant transcription factors and cytoprotective genes	Activation of Nrf2 antioxidant	Dare et al. (2021)	experimental phase, no evidence for only metformin beneficial properties, combined therapy may leads to cardiac injury

AMPK, 5′AMP-activated protein kinase; Nrf2, Nuclear factor E2-related factor 2; SIRT3, sirtuin 3.