Melatonin and Quercetin Co‐Treatment Attenuates Hepatic Damage in Diabetic Rats by Mitigating Oxidative Stress and Inflammation

Liver complications in diabetes are very common, contributing to a high mortality rate, making it essential to develop strategies to minimize this damage. We analyzed the effect of treatment with quercetin and melatonin on the liver of diabetic rats. The following groups were formed: GC-non-diabetic rats; GD-diabetic rats; GDI-diabetic rats treated with insulin; GDM-diabetic rats treated with melatonin; GDQ-diabetic rats treated with quercetin; and GDQM-diabetic rats treated with quercetin/melatonin. Insulin (5 U/day), melatonin (10 mg/kg), and quercetin (40 mg/kg) were administered for 30 days after confirmation of diabetes. Weight, histology, immunohistochemistry (IL-6, TNF-α, and IL-10), biochemistry (glycemia, AST, and ALT), morphometry, and oxidative stress were evaluated. Only animals in the GDI (89.50 ± 4.92 mg/dL) and GDM (90.75 ± 3.88 mg/dL) groups showed similar blood glucose levels to the GC group (87.50 ± 7.14 mg/dL). Liver weight was higher in the GD group (12.44 ± 1.55 g). In the GD group, TBARS levels were elevated (3.10 ± 0.93 nmol/mg), and there was a reduction in GSH (12.90 ± 1.03 nmol/mg). In GD, there was an increase in the percentage of lobular parenchyma (95.00 ± 0.90) and a reduction in non-lobular parenchyma (5.00 ± 0.45). In the diabetic group, hydropic degeneration of hepatocytes and multifocal areas of coagulative necrosis were observed. AST (88.95 ± 11.45 U/L) and ALT (68.38 ± 1.79 U/L) were elevated. IL-6 and TNF-α were elevated in GD, while IL-10 was reduced. It is concluded that treatment with melatonin and quercetin, alone or in combination, may be an adjunctive alternative in protecting the liver against diabetic complications in rats.