Preclinical points of view
Metformin improves the insulin resistance primarily in muscle, liver, and adipose tissues by reducing the liver glucose output, largely due to a diminution in the rate of glycogenolysis and gluconeogenesis (97). Various beneficial effects of metformin include attenuation of abnormal glucose metabolism, weight loss, improvement of insulin resistance, endothelial dysfunction, subclinical inflammation, lipid-lowering properties, antineoplastic potential and cardiovascular protection. Metformin itself is a non-nephrotoxic drug which was initially chosen as the safest hypoglycemic substance in chronic renal failure. However, its use has been limited in these patients because of the perceived risk of lactic acidosis (98). …show more content…
Previously, the improvement of mitochondrial homeostasis by metformin through diminishing apoptosis induced by oxidative stress and preventing cell death has been reported. The improvement of antioxidant system by complementing mitochondrial function and decreasing the depletion of respiratory components has also been revealed (110). In a preclinical study, on 50 male rats, we showed that metformin is able to prevent or improve gentamicin induced acute kidney injury (111,112). In an experimental investigation, we tested the ameliorative effects of co-administration of metformin and garlic extract for prevention of gentamicin nephrotoxicity in rats. In this experimental study, seventy male rats were tested. The results of this study revealed that metformin and garlic as well as their combination have protective and curative activity against gentamicin renal toxicity (113). Recently, to find the protective efficacy of metformin against gentamicin induced renal toxicity in rabbits, Janjua et al., conducted a preclinical study on thirty-six rabbits which were treated with metformin and gentamicin. They found that metformin offers complete renoprotection at low toxic dose ranges of gentamicin (114). More recently, to investigate the protective effect of metformin on kidney injury of mice treated with a high fat diet, Zhang et al., found that, metabolic disorders in metformin treated group were significantly improved and the renal lipids deposition and other pathological changes were ameliorated. They also found the increment of expression of phospho-AMP-activated protein kinase (P-AMPK) α protein and the significant diminution of expression of sterol regulatory element-binding protein (SERBP)-1c and TNF-α. They concluded that metformin up-regulated activity of renal AMPK, improved metabolic disorders, diminished the expression of kidney SREBP-1c and TNF-α, decreased
Metformin improves the insulin resistance primarily in muscle, liver, and adipose tissues by reducing the liver glucose output, largely due to a diminution in the rate of glycogenolysis and gluconeogenesis (97). Various beneficial effects of metformin include attenuation of abnormal glucose metabolism, weight loss, improvement of insulin resistance, endothelial dysfunction, subclinical inflammation, lipid-lowering properties, antineoplastic potential and cardiovascular protection. Metformin itself is a non-nephrotoxic drug which was initially chosen as the safest hypoglycemic substance in chronic renal failure. However, its use has been limited in these patients because of the perceived risk of lactic acidosis (98). …show more content…
Previously, the improvement of mitochondrial homeostasis by metformin through diminishing apoptosis induced by oxidative stress and preventing cell death has been reported. The improvement of antioxidant system by complementing mitochondrial function and decreasing the depletion of respiratory components has also been revealed (110). In a preclinical study, on 50 male rats, we showed that metformin is able to prevent or improve gentamicin induced acute kidney injury (111,112). In an experimental investigation, we tested the ameliorative effects of co-administration of metformin and garlic extract for prevention of gentamicin nephrotoxicity in rats. In this experimental study, seventy male rats were tested. The results of this study revealed that metformin and garlic as well as their combination have protective and curative activity against gentamicin renal toxicity (113). Recently, to find the protective efficacy of metformin against gentamicin induced renal toxicity in rabbits, Janjua et al., conducted a preclinical study on thirty-six rabbits which were treated with metformin and gentamicin. They found that metformin offers complete renoprotection at low toxic dose ranges of gentamicin (114). More recently, to investigate the protective effect of metformin on kidney injury of mice treated with a high fat diet, Zhang et al., found that, metabolic disorders in metformin treated group were significantly improved and the renal lipids deposition and other pathological changes were ameliorated. They also found the increment of expression of phospho-AMP-activated protein kinase (P-AMPK) α protein and the significant diminution of expression of sterol regulatory element-binding protein (SERBP)-1c and TNF-α. They concluded that metformin up-regulated activity of renal AMPK, improved metabolic disorders, diminished the expression of kidney SREBP-1c and TNF-α, decreased