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).