Ömer ÜNAL, Adem ATACAK, Elif GÜLBAHÇE MUTLU
Anatolian Current Medical Journal - 2026;8(5):884-891
Aims: This study aimed to evaluate the effects of intraperitoneal zinc (Zn) supplementation on hepatic structural alterations, enzymatic antioxidant capacity, and metabolic regulation in an aged diabetic rat model. Methods: Female rats aged 18 months type 2 diabetes mellitus (T2DM) was induced using a high-fat diet (HFD) and streptozotocin (STZ). The STZ+Zn group received 5 mg/kg/day of Zn sulphate intraperitoneally. Histomorphometric and histochemical evaluations of liver tissue were performed, including assessment of the N/C ratio and sinusoidal dilation, as well as staining with Masson and PAS. Immunohistochemistry was used to analyse protein levels (PGC1alpha, FTO), while qPCR was employed to examine mRNA expression (HO-1, CAT). Results: Significant improvements in sinusoidal dilatation, increased N/C ratio, glycogen depletion, and fibrosis were observed in the STZ group following Zn treatment (STZ+Zn). In the PCR analysis, the diabetic group's depleted CAT and HO-1 expressions were restored by Zn, with HO-1 levels increasing to above those of the control group (p<0.05). Furthermore, the diabetes-induced elevation of PGC1alpha was normalized by Zn, whereas the suppressed FTO protein levels remained unchanged (p>0.999). Conclusion: In the diabetic liver of older animals, administration of a 5 mg/kg intraperitoneal Zn injection improved tissue morphology, normalized PGC1alpha expression, and strongly activated the enzymatic antioxidant defense (HO-1/CAT) at the genetic level, although it was unable to restore FTO protein levels.
