Effect of Two months’ administration of BOLD and TRAM alone or in combination on serum AST and CK
Administration of BOLD and TRAM alone or their combination for 2 months significantly increased serum AST concentration (by 172.76%, 82.55%, and 339.15%, respectively) compared to normal control group. The group injected with a combination of BOLD and TRAM also showed significant increase in AST concentration, compared to BOLD and TRAM groups (Table 2).
Moreover, injection of BOLD and TRAM alone or combined significantly elevated CK concentration in serum by 137.73%, 55.94%, and 228.49% respectively, as compared to the normal control group. The group injected with a combination of BOLD and TRAM showed a significant increase in CK level when compared to groups injected with BOLD or TRAM (Table 2).
Effect of Two months’ administration of BOLD and TRAM alone or in combination on serum lipid profile
Rats injected with BOLD showed a significant increase in serum cholesterol and TG concentrations, by 104.4% and 111.59% respectively, compared to the normal control group. On the other hand, administration of TRAM and BOLD reduced serum HDL concentration prominently, by 32.6% and 16.58% correspondingly compared to the normal control group.
Intraperitoneal injection of TRAM did not show any significant change in serum cholesterol or TG levels as compared to the normal control group. Injection of BOLD in combination with TRAM markedly elevated cholesterol and TG serum levels, by 37.2% and 199.53% respectively, compared to the normal control group. Moreover, this combination significantly raised serum cholesterol and TG, by 51.1% and 57.6% respectively, when compared to the group injected TRAM only. It was also recorded that the group injected only with BOLD showed the highest increase in both cholesterol and TG compared to all other groups (Table 2). Serum HDL concentration was significantly decreased by concurrent administration of BOLD and TRAM by 26.73% as compared to the normal control group. Likewise, this combination showed a significant reduction in HDL level when compared to TRAM group by 12.18%. Interestingly, the group injected with BOLD, only showed the greatest reduction in HDL serum levels as compared to all other groups (Table 2).
Effect of Two months’ administration of BOLD and TRAM alone or in combination on oxidative stress and nitrosative biomarkers
Effect on MDA
Intraperitoneal injection of BOLD and TRAM for two months significantly increased MDA concentration in cardiac tissue by 162.36% and 146.35% respectively as compared to the normal control group showing. Combination of BOLD and TRAM showed a significant increase in MDA concentration by 184.34% as compared to the normal control group. Moreover, this combination exhibited significant increase in MDA concentration as compared to TRAM group. On the other hand, no significant change was recorded when compared to BOLD group (Table 3).
Effect on reduced glutathione (GSH)
Administration of BOLD and TRAM for two months significantly reduced GSH concentration in cardiac tissue, as compared to normal control group, by 62.4% and 63.45% respectively. Mixture of BOLD and TRAM showed a significant decrease in GSH concentration by 79.27% compared to normal control group. Likewise, combination of BOLD and TRAM showed a significant decrease in GSH level when compared to BOLD or TRAM groups (Table 3).
Effect on superoxide dismutase (SOD)
Injection of BOLD and TRAM diminished SOD concentration in cardiac tissue, compared to normal control group by 53% and 52.71% respectively. Co-administration of BOLD and TRAM showed a significant decrease in SOD concentration by 63.23% compared to the normal control group. Likewise, this combination showed no significant change in SOD level when compared to BOLD or TRAM groups (Table 3).
Effect on nitrous oxide (NO)
Intraperitoneal injection of BOLD and TRAM for two months increased NO concentration in cardiac tissue by 111.59% and 128.37% respectively, compared to normal control group. Combination of BOLD and TRAM amplified NO concentration by 199.53% as compared to the normal control group. Conversely, this combination showed no significant change in NO level when compared to groups injected with BOLD or TRAM (Table 3).
Assessment of inflammatory cytokines (TNF-α and IL-6)
TNF-α concentration in cardiac tissue significantly improved in BOLD and TRAM groups by 188.28% and 186.21% correspondingly, compared to normal control group. Moreover, Combination of BOLD and TRAM showed a significant increase in TNF-α concentration 461.86% compared to the normal control group. Also, this combination showed a noteworthy elevation in TNF-α concentration, compared to both BOLD and TRAM groups (Table 4).
IL-6 concentration in cardiac tissue significantly increased after two month administration of BOLD and TRAM by 146.89% and 158.57% respectively, compared to normal control group.
Co-administraion of BOLD and TRAM showed a significant increase in IL-6 concentration by 277.76% compared to the normal control group. This combination of BOLD and TRAM also showed a significant increase in IL-6 concentration, as compared to both BOLD and TRAM groups (Table 4).
Histopathological study
Cardiac tissue of normal control group showed normal histological structure of the myocardial cells in bundles (Fig. 2). The group injected with BOLD for two months showed congestion in the myocardial blood vessels (Fig. 3a) associated with thickening and sclerosis in the vascular wall (Fig. 3b). The group injected with TRAM exhibited myocardial degeneration (Fig. 4a), associated with severe dilatation and congestion of the myocardial blood vessels (Fig. 4b). Hypertrophy was detected in some focal areas in the myocardial cells (Fig. 4c). There was also thickening and sclerosis in the wall of the myocardial blood vessels (Fig. 4d). The group injected with a combination of BOLD and TRAM showed apparent congestion in the myocardial blood vessels (Fig. 5).