Diabetes and hypertension account for the majority of chronic kidney injury cases that can lead to renal failure. The link between the leukocytes common antigen (CD45) and diabetic kidney disease (DKD) with and without metformin incorporation in an animal model has not been investigated before. Therefore, we sought to assess the extent of leukocytes infiltration into kidney tissues 10 weeks following the induction of diabetes in rats treated with metformin. In addition, we monitored blood and urine parameters associated with diabetes. The model group of rats received streptozotocin (STZ; 50 mg/kg) injection after being fed for 14 days on a high-fat diet (HFD) and continuously fed a HFD until they were culled, at week 12. The protective group was treated in the same way except that these animals were put from day 1 on metformin (200 mg/kg) until being culled, on week 12. Kidneys were immunostained with CD45 as a marker of leukocytes infiltration and examined by light microscopy. Urine samples were tested for urine albumin and collected blood was analyzed for sugar, urea, creatinine, and oxidative stress and antioxidants biomarkers. Kidney injury secondary to diabetes was developed as demonstrated by (i) increased blood glucose, urea, and malondialdehyde (MDA) as a marker of lipid peroxidation; and (ii) kidney tissue damage and marked increase in kidney tissues expressing CD45 positive cells. The above markers were inhibited (p≤0.0006) by metformin. Also, a significant correlation was observed between CD45 score and glycemia, urea, MDA, and the antioxidant superoxide dismutase (SOD). Thus, our data demonstrate an association between the infiltration of CD45+ inflammatory cells into kidney tissues and biomarkers of kidney damage in a rat model of DKD, which was effectively protected by metformin.
KEY WORDS: Diabetes; Kidney injury; CD45; Oxidative stress; Metformin; Rat model.
MOMENAH, M. A. Suppression of diabetes-induced renal inflammatory cell infiltration by metformin associated with the amelioration of renal injury biomarkers. Int. J. Morphol., 40(4):874-879, 2022.