Toxicity and Safety Evaluation of Doxorubicin-Loaded Cockleshell-Derived Calcium Carbonate Nanoparticle in Dogs

Figure 11

Electron micrograph (TEM) of the left ventricular myocardial tissue section and kidney section. (a) Myocardial tissue section of dogs given normal saline showing clear distinct cisternae on the mitochondria, with spindle-shaped nucleus within the myofilament and the proximal convoluted tubules of the dogs given normal saline revealing its lumen and apical cellular membrane with microvilli appearing normal with distinct mitochondrial cisternae and nerves surrounded by myelin sheaths. (b) Free DOX 150 mg/m² showing extensive mitochondrial damage and rupture with marked swelling and cristae disorientation, scattered vacuolated cardiomyocyte, with free empty vacuum and Z-band aggregate in close cluster to ribosome in the cytoplasm with the dilated proximal convoluted tubules with vesicle and distorted cristae in the mitochondria. (c) CS-CaCO₃NP-DOX 250 mg/m² showing mitochondrial rupture with cristae disorientation with free empty vacuum with few dilated proximal convoluted tubules and shrinked apical microvilli and vesicle and sarcoplasmic tubules. (d) CS-CaCO₃NP-DOX 150 mg/m² showing clear distinct cisternae on the mitochondria, with sarcoplasmic tubules, myofilament with the renal nucleus with distinct peripheral distribution of chromatic material and normal appearance with mild swollen mitochondrial and rough endoplasmic reticulum with a normal basement membrane thickness. (e) CS-CaCO₃NP-DOX 100 mg/m² showing clear distinct cisternae on the mitochondria, with sarcoplasmic tubules, myofilament with the normal appearance of renal tissue with mild swollen mitochondrial and rough endoplasmic reticulum with a normal basement membrane thickness (1 µm).

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