Effects of SLY on body, liver, and kidney weights in 5-FU-toxicity
The live weights of the mice were similar among to groups. Liver weights reduced to 5-FU group so far as control but this decreasing not statistically significant. Liver weights of the SLY10+5-FU group were higher than the 5-FU group (p<0.05). Also, were similar among to groups (Table 1).
Table 1. The body, liver, and renal weights in experimental groups (a,b: p <0.05).
Experimental Groups
|
Body weight (g)
|
Liver weight (g)
|
Renal weight (g)
|
Control
|
37,4±2,5a
|
1,8±0,13ab
|
0,43±0,05a
|
5-FU
|
34,1±1,4a
|
1,6±0,10a
|
0,43±0,04a
|
SLY50+5-FU
|
34,5±2,1a
|
1,8±0,13ab
|
0,46±0,04a
|
SLY100+5-FU
|
36,3±2,1a
|
1,9±0,11b
|
0,45±0,0,06a
|
Effects of SLY on liver enzymes and renal function parameters
Serum ALT, AST, total bilirubin, urea, and creatinine levels were markedly increased in the 5-FU and SLY50+5-FU groups according to control. In the SLY100+5-FU group lower levels of these parameters by comparison to 5-FU and SLY50+5-FU groups (Table 2).
Table 2. Liver and kidney function parameters of mice in experimental groups ( a,b: p <0.01; a,c; b,c: p <0.05).
Experimental Groups
|
ALT
(IU/L)
|
AST
(IU/L)
|
Total Bilirubin
(mg/dl)
|
Urea
(mg/dl)
|
Creatinine (mg/dl)
|
Control
|
33,2±4,7a
|
134,1±9,7a
|
1,2±0,3a
|
35,6±3,2a
|
0,32±0,05a
|
5-FU
|
46,8±4,9b
|
241,1±20,8 b
|
2,2±0,4b
|
64,3±6,3b
|
0,49±0,08b
|
SLY50+5-FU
|
44,8±2,7b
|
170,1±21,3c
|
1,8±0,2b
|
48,9±8,9c
|
0,43±0,05b
|
SLY100+5-FU
|
35,8±3,1a
|
158,1±25,1ac
|
1,3±0,2a
|
38,4±5,2ac
|
0,35±0,03a
|
Effects of SLY on liver MDA and GSH levels
MDA levels were significantly higher in 5-FU and SLY50 + 5-FU groups compared to control, lower in SLY50 group than 5-FU group, but there was no significant difference (p> 0.05). MDA level was higher than control in SLY100 + 5-FU group. However, it is lower than the 5-FU group (Figure 1A). Also, liver GSH levels decreased significantly in the 5-FU and SLY50 + 5-FU groups up to the control and SLY100 + 5-FU groups (Figure 1C).
Effects of SLY on liver SOD, CAT, and GR activities
Liver SOD, CAT, and GR activities were markedly lower in the 5-FU group in comparison with control. These enzyme activities increased in the SLY50+5-FU and SLY100+5-FU groups according to the 5-FU group (p˂0.05) and these effects of SLY were dose-dependent and higher doses of SLY more significantly prevented the 5-FU-induced reduction in antioxidant enzyme activities (Figure 1B, 1D, 1E).
Effects of SLY on renal MDA and GSH levels
MDA levels in 5-FU and SLY50+5-FU groups had significantly higher according to the control and were lower in the low dose group of SLY than 5-FU group (p˂0.05). MDA level in SLY100+5-FU group reduced according to 5-FU (Figure 2A). Renal GSH levels reduced significantly in the 5-FU and SLY50+5-FU groups so far as to control and SLY100+5-FU groups (Figure 2C).
Effects of SLY on renal SOD, CAT, and GR activities
Renal SOD, CAT, and GR activities were significantly lower in the 5-FU group in comparison with others groups. These enzyme activities increased in the SLY50+5-FU and SLY100+5-FU groups according to the 5-FU group (p>0.05) and these effects of SLY were dose-dependent (Figure 2B, 2D, 2E).
Histopathological findings
When the liver and kidney tissues of the control group were examined to histopathologically, it was observed that they were in normal histological structures (Figure 3-4 A). In 5-FU groups, especially in the acinar region of the liver and hepatocytes were observed to severe degeneration, necrosis, and vascular hyperemia (Figure 3B). In the liver sections of SLY50+5-FU group, moderate degeneration, mild necrosis, and hyperemia in the vessels were detected in hepatocytes (Figure 3C). When the liver tissues of SLY100+5-FU group were examined histopathologically, mild degeneration in the hepatocytes and mild hyperemia in the vessels were observed (Figure 3D). The renal tubular epithelium of mice in the 5-FU group were observed severe hydropic degeneration and coagulation necrosis and were detected severe hyperemia in the glomerular and interstitial vessels (Figure 4B). The renal tubular epithelium of the SLY50+5-FU group was detected moderate degeneration, necrosis, and severe hyperemia in interstitial and glomerular vessels (Figure 4C). When the kidney tissues of the SLY100+5-FU group were examined histopathologically, mild degeneration in the tubular epithelium and mild hyperemia in the interstitial and glomerular vessels were determined (Figure 4D). A significant difference (p˂0.05) was detected when compared with the 5 FU groups (Table 3).
Immunohistochemical findings
When liver and kidney tissues of the control group were examined immunohistochemically, 8-OHdG and IL-6 expression in liver tissues (Figure 5-6A) and kidney tissues (Figure 7-8A) were negative. Severe cytoplasmic 8-OHdG expression was detected in hepatocytes in the liver, acinar region, in the 5-FU group (Figure 5B). Also, severe IL-6 expression was observed in the liver at sinusoidal and portal intervals (Figure 6B). In the 5-FU group was viewed severe cytoplasmic 8-OHdG expression in kidney tubular epithelium (Figure 7B), severe IL-6 expression in the glomerulus, intertubular intervals, and vascular circumference (Figure 8B). In the SLY50+5-FU group were observed moderate cytoplasmic 8-OHdG expression in liver hepatocytes (Figure 5C) and in this group was detected moderate IL-6 expression in the sinusoidal spaces, vascular environment and portal spaces (Figure 6C). The SLY50+5-FU group were determined moderate cytoplasmic 8-OHdG expression in the tubular epithelium (Figure 7C), moderate IL-6 expression in glomeruli, intertubular intervals, and vascular circumference (Figure 8C). In livers of SLY100+5-FU group were determined mild cytoplasmic 8-OHdG expression in the tubular epithelium (Figure 5D), sinusoidal intervals and in the portal region was detected to IL-6 expression at mild level (Figure 6D). In the SLY100+5-FU group, in the kidney tissues were observed 8-OHdG expression in the cytoplasmic mild level in the tubular epithelium (Figure 7D), and were determined to mild IL-6 expression in the glomerulus, intertubular intervals, and vascular circumference (Figure 8D). A significant difference (p˂0.05) was detected when compared with the control group. Immunohistochemical findings are summarized in table 3.
Table 3. Scoring of histopathological and immunohistochemical findings of liver and kidney tissues
|
Parameters
|
Control
|
5-FU
|
SLY50+5-FU
|
SLY100+5-FU
|
Liver
|
Degeneration in hepatocytes
|
-
|
+++
|
++
|
+
|
Necrosis in hepatocytes
|
-
|
+++
|
+
|
-
|
Hyperemia in the vessels
|
-
|
+++
|
+++
|
++
|
8-OHdG expression
|
-
|
+++
|
++
|
+
|
IL-6 expression
|
-
|
+++
|
++
|
+
|
Kidney
|
Degeneration in tubules epithelium
|
-
|
+++
|
++
|
+
|
Necrosis in tubules epithelium
|
-
|
+++
|
+
|
-
|
Hyperemia in the vessels
|
-
|
+++
|
+++
|
++
|
8-OHdG expression
|
-
|
+++
|
++
|
+
|
|
IL-6 expression
|
-
|
+++
|
++
|
+
|