## 6 Results
### Effects of FidHycarn on Cytokine and Chemokine Levels after OA Induction  
A substantial increase in TNF-\(\alpha\), IL-1\(\beta\), IL-6, MIP-l\(\alpha\), and MIP-2 production was found in OA subjected rats 21 days post MIA injection. The levels of cytokines and chemokines were not significantly reduced in MIA rats treated orally with carnosine (17.6 mg/kg), carnosine+HA (17.6 + 70.9 mg/kg), and HA (70.9 mg/kg). On the contrary, oral FidHycarn treatment was able to reduce these levels. The effect of FidHycarn at 88.5 mg/kg on TNF-\(\alpha\), IL-6, and MIP-1\(\alpha\) levels was statistically different to the naproxen treatment but no statistical difference was observed on IL-1\(\beta\) and MIP-2 levels. Low levels were found in the Sham animals (Figure 7).  
The Effects of FidHycarn on Nitrotyrosine, INOS, IL-1\(\beta\), and IL-6 Expression after OA Induction  
A significant positive staining for nitrotyrosine, iNOS, IL-1\(\beta\), and IL-6 was found in MIA rats treated with the vehicle (Figure 6, Figure 7, Figure 8, Figure 9B, and see H). Oral treatments of carnosine (17.6 mg/kg), carnosine+HA (17.6 + 70.9 mg/kg), and HA (70.9 mg/kg) were not able to reduce this positive staining (Figure 8, Figure 9, Figure 10, Figure 11C-E, and see H). Instead, oral FidHycarn treatment at 88.5 mg/kg showed an important reduction of positive staining for nitrotyrosine, iNOS, IL-1\(\beta\), and IL-6 compared to the others (Figure 8, Figure 9, Figure 10, Figure 11F, and see H). The effect of FidHycarn at 88.5 mg/kg was statistically different to the Naproxen treatment (Figure 8, Figure 9, Figure 10, Figure 11G, and see H). No positive staining was discovered in the Sham group (Figure 8, Figure 9, Figure 10, Figure 11, and see H).  
Figure 7: The effects of FidHycarn on cytokine and chemokine production. TNF-\(\alpha\) (**A**), IL-1\(\beta\) (**B**), IL-6 (**C**), MIP-l\(\alpha\) (**D**) and MIP-2 (**E**) levels were shown. Values are given as mean \(\pm\) SEM of 20 animals for each group \(\texttt{{}^{***}}\)\(p\)\(<\) 0.001 versus Sham; \(\texttt{{}^{***}}\)\(p\)\(<\) 0.001 versus MIA.  
Figure 8: The effects of FidHycam on nitrotyrosine expression. Immunohistochemistryistochemistry for nitrotyrosine in joint tissues: (**A**) Sham group, (**B**) MIA group, (**C**) MIA+Carnosine, (**D**) MIA+Carnosine+HA, (**E**) MIA+HA, (**F**) MIA+FidHycam treatment group, (**G**) MIA+Naproxen. The results are expressed as a % of positive pixels (**H**). Figures are representative of at least three independent experiments. *** \(p<0.001\) versus Sham; *** \(p<0.001\) versus MIA.  
Figure 9: The effects of FidHycam on iNOS expression. Immunohistochemistryistochemistry for iNOS in joint tissues: (**A**) Sham group, (**B**) MIA group, (**C**) MIA+Carnosine, (**D**) MIA+Carnosine+HA, (**E**) MIA+HA, (**F**) MIA+FidHycam treatment group, (**G**) MIA+Naproxen. The results are expressed as a % of positive pixels (**H**). Figures are representative of at minimum three independent experiments. *** \(p<0.001\) versus Sham; *** \(p<0.001\) versus MIA.  
Figure 11: The effects of FidHycarm on IL-6 expression. Immunohistochemistryistochemistry for IL-6 in the joint tissues: (**A**) Sham group, (**B**) MIA group, (**C**) MIA+Carnosine, (**D**) MIA+Carnosine+HA, (**E**) MIA+HA, (**F**) MIA+FidHycarm treatment group, (**G**) MIA+Naproxen. The results are expressed as a % of positive pixels (**H**). Figures are representative of at minimum three independent experiments. *** \(p<0.001\) versus Sham; *** \(p<0.001\) versus MIA.  
Figure 10: The effects of FidHycarm on IL-1 expression. Immunohistochemistryistochemistry for IL-19 in the joint tissues: (**A**) Sham group, (**B**) MIA group, (**C**) MIA+Carnosine, (**D**) MIA+Carnosine+HA, (**E**) MIA+HA, (**F**) MIA+FidHycarm treatment group, (**G**) MIA+Naproxen. The results are expressed as a % of positive pixels (**H**). Figures are representative of at least three independent experiments. *** \(p<0.001\) versus Sham; *** \(p<0.001\) versus MIA.