Clinicopathological Studies on the Impact of Grape Seed Extract and L-Carnitine as Cardioprotective Agents Against Doxorubicin-Induced Toxicity in Rats

Figure 1. Phytochemical analysis of grape seed extract.

Figure 2. (A) Representative ECG on day 29 of the experiment. (B) Representative ECG on day 35 of the experiment. Group GSE: grape seed extract, Group L-CA: L-Carnitine; Group DOX: Doxorubicin; Group GSE + DOX: Grape seed extract with Doxorubicin, Group L-CA+ DOX: L-Carnitine with Doxorubicin. Labels a, b, and c denote the following ECG parameters: (a) ST-segment elevation, (b) QRS interval and (c) QT interval.

Figure 3. The impact of doxorubicin, grape seed extract, and L-carnitine on heart rate (HR), QRS complex, QT interval, and ST segment amplitude. (A) Representation of the changes in ECG on day 29 of the experiment (n = 5). Data for each rat were obtained from 4 readings/rat. (B) Representation of the changes in ECG on day 35 of the experiment (n = 5). Data for each rat were obtained from 4 readings/rat.

Figure 4. Photomicrographs of cardiac myocytes from the control, GSE, and L-CA groups (a–c) on day 29 of the experiment displayed normal cardiac myofibrillar structure (MF) with striations, branched appearance, central nucleus, and continuity with adjacent myofibrils. In contrast, the DOX group (d) revealed several abnormalities, including nuclear pyknosis and leukocyte infiltration (indicated by arrows). The DOX + GSE and DOX + L-CA groups (e,f) showed a restoration to normal cardiac myofibrillar structure (C) with clear striations. (H&E, 400×).

Figure 5. Photomicrographs of cardiac myocytes from the control, GSE, and L-CA groups (a–c) on day 35 of the experiment showed normal cardiac myofibrillar structure (MF) with striations, a branched appearance, a central nucleus, and continuity with adjacent myofibrils. In contrast, the DOX group (d) exhibited signs of myocardial infarction, including focal myolysis, non-visible nuclei, and darker, irregular necrotic contraction bands (indicated by arrowheads). The DOX + GSE and DOX + L-CA groups (e,f) displayed a return to normal cardiac myofibrillar structure (C) with clear striations. (H&E, 400×).

Figure 6. Photomicrographs of Masson-trichrome-stained cardiac myocytes of low and high magnification from the control (a,g), GSE (b,h), and L-CA groups (c,i) on day 35 of the experiment depicted normal cardiac myofibrillar structure with striations, a branched appearance, a central nucleus, and continuity with adjacent myofibrils. In contrast, the DOX group (d,j) exhibited interstitial fibrosis, with an increase in the percentage area of collagen fiber (arrow). However, the GSE + DOX (e,k) and L-CA + DOX groups (f,l) displayed a restoration of normal cardiac myofibrillar structure with clear striations, accompanied by a decrease in the percentage area of collagen fiber. (100× & 400×). The mean percentage area of collagen fiber (m) was quantified across (n = 5) rats/group. Each set of rat data was obtained from 12 measurements. Group GSE: grape seed extract; Group L-CA: L-Carnitine; Group DOX: Doxorubicin; Group GSE + DOX: Grape seed extract with Doxorubicin; Group L-CA + DOX: L-Carnitine with Doxorubicin.