header image
 

All posts in August, 2018

Body weight of the host and haematological parameters

As shown in Table 1, the results indicated that intraperitoneal ad- ministration of DOX-significantly (P < 0.05) decreased the body weight, reduced the number of circulating RBCs, WBCs and Hb level as well as neutrophil and lymphocyte count relative to the vehicle control group. Whereas, oral administration of I3C in concomitant and pre- treatment schedule significantly increased the body weight (P < 0.05), RBCs, WBCs, hemoglobin level as well as neutrophil and lymphocyte count compared to only DOX-treated mice.

DOX-administration significantly (P < 0.05) depleted the bone marrow, thymus and spleen cell count by 32.30%, 20.08% and 21.24% respectively compared to vehicle control group (Table 2). However, oral administration of I3C in concomitant treatment schedule significantly (P < 0.05) increased the bone marrow, thymus and spleen cell count by 25.29%, 16.70% and 15.82% respectively compared to only DOX-treated mice. In addition, pretreatment with I3C most significantly (P < 0.05) increased the bone marrow, thymus and spleen cell count by 31.49%, 19.29% and 19.60% respectively com- pared to only DOX-treated group.

Amelioration of serum CPK, CK-MB, ALT, AST and ALP activity

The cardiac functions were severely impaired by DOX-administra- tion, as illustrated in the Table 3. Results showed that DOX-adminis- tration significantly (P < 0.05) raised the CPK and CK-MB activity by 60.62% and 38.92% respectively compared to vehicle control group (Table 3). However, concomitant treatment with I3C significantly (P < 0.05) reduced the activity of CPK and CK-MB by 29.26% and 23.10% respectively whereas in pretreatment schedule more sig- nificantly (P < 0.05) reduced the CPK and CK-MB activity by 51.67% and 35.43% respectively, compared to only DOX-treated mice.

DOX-administration significantly (P < 0.05) elevated the activity of serum ALT (51.55%), AST (34.00%) and ALP (39.21%) compared to vehicle control group (Table 3). Whereas, mice treated with I3C in concomitant treatment schedule significantly (P < 0.05) decreased the ALT, AST and ALP activity by 23.50%, 17.62% and 25.03% respectively compared to the only DOX-treated group. In addition, pretreatment with I3C significantly (P < 0.05) decreased the ALT, AST and ALP activities by 49.16%, 31.48% and 35.78% respectively in comparison to the only DOX-treated mice.

Attenuation of cardiac LPO level

Mice treated with DOX, the cardiac LPO level was significantly (P < 0.05) elevated by 84.15% compared to vehicle control group (Fig. 7A). However, oral administration of I3C in concomitant and pretreatment schedule significantly (P < 0.05) depleted the cardiac LPO level by 39.20% and 65.98% respectively compared to only DOX- treated mice.

Reduced glutathione level

DOX-treatment significantly depleted the cardiac GSH level by 57.25% as compared to vehicle control group (Fig. 7B). Whereas, concomitant and pretreatment with I3C significantly (P < 0.05) in- creased the GSH level by 36.08% and 53.38% respectively in compar- ison to the only DOX-treated group.

Intensification of cardiac antioxidant enzymes activity
In cardiac tissues, DOX-administration significantly (P < 0.05) decreased the antioxidant enzyme viz., GST, GPx, SOD and CAT activity by 41.86%, 50.00%, 52.48% and 56.76% respectively compared to vehicle control group. However, oral administration of I3C in con- comitant treatment significantly (P < 0.05) elevated the GST, GPx, SOD and CAT activity by 30.53.08%, 31.70%, 36.20% and 39.26% respectively, compared to only DOX- treated mice. In addition, pre- treatment with I3C more significantly (P < 0.05) increased the GST, GPx, SOD and CAT activity by 40.41%, 44.00%, 51.47% and 52.26% respectively compared to only DOX-treated mice (Fig. 7C–F). Sublingual

Histopathological findings
DOX-induced myelosuppression and genotoxicity was further confirmed by bone marrow histology. Administration of DOX-increased myeloid hyperplasia, hemorrhages and diffuse infiltration with in- flammatory cells (mostly mature lymphocytes) in a representative femur. However, experimental results showed that oral administration of I3C significantly mitigating bone marrow suppression by reduced the myeloid hyperplasia and hemorrhage reduction in the bone marrow cells (Fig. 1B).

DOX-induced cumulative cardiotoxicity was confirmed by histo- pathological evaluation. Vehicle control group showed normal cardio- myocyte appearance. The cardiac muscle fibres were found to be uni- form size and shape with no vacuolated cells. There was no necrosis and no inflammatory cell infiltrates were present. However, DOX-adminis- tration caused massive cardiomyocyte degeneration, swelling of the myocardial fibers, inter-muscular edema, inter-muscular hemorrhage, diffuse infiltration with inflammatory cells (mostly mature lympho- cytes) (Fig. 6C). This picture was significantly improved in mice after oral administration of I3C evidenced by less morphological changes such as patchy and scattered vacuolation restricted to subendocardial layers and decreased number of inflammatory cells.

Normalization of DOX-induced hypertrophy in cardiac tissue

Cardiac hypertrophy is the abnormal swelling or thickening of the heart muscle and changes in other components, such as extracellular matrix resulting from increases in size, as an adaptive response to a number of intrinsic and extrinsic stimuli. It is characterized by in- creased protein synthesis, sarcomeric reorganization and re-expression of fetal regulatory genes. Extended pathological cardiac hypertrophy is a major cardiovascular endpoint and is strongly associated with arrhythmias, heart failure and sudden death. In corroborating with the previous findings results of the study showed that DOX-administration increased the cardiac hypertrophy, a dose-limiting side effect, by the formation of free-radicals and lipid peroxidation. In contrast, co-ad- ministration of I3C in concomitant and pretreatment schedule, these abnormal pathological conditions were normalized by protection of the cardiac tissue from oxidative damage (Fig. 8A).