Effect of Cinnamic Acid on Kidney Tissue, GSTK1 and GSTT1 in Type 1 Diabetes Rat Model: A Histochemical and Immunohistochemical Investigation

Type 1 diabetes is a chronic disease that results from the autoimmune destruction of insulin-producing pancreatic β-cells and requires lifelong insulin therapy. Among the long-term microvascular complications associated with diabetes, diabetic nephropathy (DN) is one of the most prevalent and serious. DN is a major clinical condition characterized by degenerative changes in glomerular and tubular structures and can progress to end-stage renal disease (ESRD) over time. Hyperglycemia induced by T1D exerts damaging effects on cellular metabolism through oxidative stress, inflammatory responses, and apoptosis, ultimately leading to structural and functional deterioration in kidney tissue. This thesis aimed to investigate the effects of cinnamic acid, a natural polyphenolic compound with antioxidant properties, on kidney tissue and the expression levels of glutathione S-transferase kappa 1 (GSTK1) and glutathione S-transferase theta 1 (GSTT1) in 8–12-week-old male Wistar albino rats with streptozotocin (STZ)-induced T1D. A total of 32 rats were divided into four groups: control, diabetes, diabetes + cinnamic acid, and cinnamic acid only, and appropriate experimental procedures were applied. Histopathological evaluation of H&E, PAS, and trichrome staining revealed no advanced alterations in any of the groups. The control and cinnamic acid groups showed normal renal histology. In the diabetes group, Bowman's capsule expansion, intertubular hemorrhage, tubular vacuolization, and degeneration were observed. These pathological changes were milder in the diabetes + cinnamic acid group, suggesting improved preservation of renal structure. PAS staining revealed partial changes such as thickening of the glomerüler basement membrane, an increase in mesangial cell count, and partial epithelial shedding in the proximal tubules in the diabetes group. Partial luminal dilatation in distal tubules was noted in both the diabetes and diabetes + cinnamic acid groups. Cinnamic acid treatment partially alleviated these findings. Although no distinct signs of fibrosis were observed with trichrome staining, a mild increase in collagen was noted in the diabetic group, which was reduced in the cinnamic acid-treated group. Vacuolization observed in the diabetic group was also diminished in the diabetes + cinnamic acid group. Immunohistochemical analysis revealed prominent GSTK1 expression in the proximal tubular epithelium across all groups. In the diabetes and diabetes + cinnamic acid groups, GSTK1 expression in glomerüler areas was more diffuse, while it was weaker in the control group. GSTT1 expression was weak in the control and cinnamic acid groups, stronger in the diabetic group, and moderate in the diabetes + cinnamic acid group. In the proximal convoluted tubule epithelium, staining intensity was higher than in the control and cinnamic acid groups but lower than in the diabetic group. These findings indicate that cinnamic acid may play a protective role against oxidative stress-induced kidney damage in T1D and may support detoxification processes by modulating the expression of antioxidant defense enzymes such as GSTK1 and GSTT1. Furthermore, the results provide scientific evidence supporting the potential of cinnamic acid as a natural antioxidant agent in the prevention of diabetes-related complications.