Histopathology and Immunoexpression of some Markers of Renal Fibrosis in the Hyperhomocysteinemic Sand Rat Model

Several studies have shown that hyperhomocysteinemia (Hhcy), a risk factor for cardiovascular diseases, is also linked to other pathologies, including the aggravation of renal lesions in humans and some animal models.To our knowledge, no studies have been conducted on the potential impact of Hhcy on renal fibrosis and tissue remodeling in sand rats (Psammomys obesus).The aim of this study was to analyze renal histopathology as well as the immunoexpression of some fibrosis markers during Hhcy in sand rats.Hhcy was induced in this species by intraperitoneal administration of methionine (150 mg/kg body weight/day) for three months.The kidney removed at the end of the experiment was subjected to histomorphometric (Masson's trichrome staining, Sirius red) and immunohistochemical (collagen I and III, -SMA, MMP-2 and -9) studies.Our results showed that the kidney of Psammomys Hhcy is the site of significant interstitial fibrosis, leukocytic infiltration, and disorganization of tubular and corpuscular structures.Immunohistochemistry revealed the involvement of type I and III fibrillar collagen in the development of fibrosis.Strong cytoplasmic immunoexpression of collagen I and III in inflammatory cells and -SMA in the renal interstitium indicated the involvement of both leukocytes and myofibroblasts in the fibrosis process.Furthermore, we observed a decrease in MMP-2 and -9 immunoexpression in tubular cells and an increase in interstitial tissue and inflammatory cells.In conclusion, the kidneys of Psammomys obesus exhibited fibrosis and tissue remodeling secondary to Hhcy.