3. Results
The changes of some biomarkers levels in the urine are presented in Table 1. The α-GST, IL-18, KIM-1, NGAL and RBP levels were significantly increased compared to the control group due to GM administration in the urine (p<0.05). Resatorvid treatment decreased IL-18, KIM-1, NGAL levels statistically (p<0.05) and partially decreased the RBP level compared to the gentamicin group. The alpha-lipoic acid treatment statistically significant decreased KIM-1 level and partially decreased α-GST, NGAL and RBP levels compared to the gentamicin group.
The changes of some biochemical parameters levels in serum and urine are presented in Table 2. In serum biochemistry, GM treatment increased statistically the glucose level and partially increased urea level compared to control group (p<0.05). However, resatorvid and ALA treatments had no effect on these parameters. In urine biochemistry, GM treatment increased statistically µALB, Crea and protein levels (p<0.05), and creatinine clearance partially decreased compared to the control group. Resatorvid and alpha-lipoic acid treatment partially decreased creatinine levels compared to the gentamicin group.
Resatorvid (5 mg/kg, intrapreitoneal) and Alpha-lipoic acid (100 mg/kg, oral) treatments caused to changes in the gene expressions of NF-κB, NRF-2, CAS-3, NR4A2 in the kidney in GM induced nephrotoxicity (Table 3). NF-κB, NRF-2, CAS-3, NR4A2 expressions were statistically increased in gentamicin group compared to the control group (p<0.05). Resatorvid treatment statistically reduced the expression of these genes compared to the gentamicin group, and alpha lipoic acid treatment statistically decreased the NRF-2, CAS-3, NR4A2 expressions compared to the gentamicin group, and partially decreased the expression of NF-κB.
Histopathological changes in all groups are shown in figure 1. The glomerulus of the control group rats was healthy as histological however some veins were slightly enlarged. Mild degeneration and mononuclear cell infiltrations were observed in the glomerulus of the gentamicin group. Severe bleeding area was detected in the subcapsular region of two rats in gentamicin groups. Degeneration and necrosis were detected in the tubules around the bleeding area. The dilatation and epithelial desquamation in tubules, hyaline casts in the lumens, and hyaline droplets in tubular epithelium were determined. Severe mononuclear cell infiltrations with inflammatory edema were detected in the intertubular area, especially in the periarteriolar region. Hyperemia in the vessels and hyaline casts in the ducts was observed. Histopathological changes similar to the gentamicin group were observed in the renal tissues of the rats in the sham group. Less hyaline casts were seen in the tubule lumens of the ALA-treated group compared to the gentamicin group. Dilatation, degeneration and necrosis of the tubules in the ALA-treated group decreased compared to the gentamicin group (Table 5, p<0.05). Focal mononuclear cell infiltrates mostly around the vessels were observed. Although resatorvid didn’t cause degeneration in the glomerulus, atrophy that does not cause dysfunction was determined in some glomerulus. In addition, it was observed that resatorvid treatment improved pathological changes in tubules, compared to the gentamicin group (Table 5, p<0.05). However, resatorvid treatment partially reduced intratubular hyaline caste (Table 5, p>0.05).