Zinc's protective role against hydroxychloroquine-induced cardiac effects in adult male albino rats

Figures

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  Fig. 1. Displays photomicrographs of sections of rat myocardium from different treatment groups. Panel A shows the control group, where the myocardium exhibits bifurcating and anastomosing longitudinal muscle fibers (arrows) with central oval nuclei (arrow heads). Cells with elongated nuclei (star) are also visible. Panel B shows myocardium from the HCQ-treated group (group II), where some myocytes have intensely eosinophilic cytoplasm (arrows) and pyknotic nuclei (arrow heads). The section also displays zones of hemorrhage and extravasated blood (B), as well as focal zones of damage and cytolysis of myocytes (D). Cells with elongated nuclei (star) are present. Panel C shows cardiac myocytes from group II with wavy myofibrils, striations (arrows), a branched look, discontinuity with neighboring myofibrils, and oval nuclei (n). Cellular leukocyte infiltration (I) and edema (E) are widespread, and fibroblast-like cells with elongated nuclei (star) are visible. Panel D shows cardiac myocytes from group II, where myofibrillar structures (arrows) exhibit vacuolations (V) and pyknotic nuclei (arrowheads). Widened areas between longitudinal cardiac muscle fibers with degeneration zones (D) are…

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  Fig. 2. Photomicrographs of CD 117 stained of rat cardio-myocytes: In panel A of the control group (I) classic CD117(+) spindle-shaped cells TCs (arrows), small nucleated bodies, and very elongated and thin moniliform processes (telopodes) (arrow heads) are observed in the intersitium between cardiac muscle fibers with oval nuclei(n). In panel B of the HCQ treated group (II), there is a compact meshwork of CD117 (+) TCs (arrows) with prominent elongated and moniliform telopodes (arrow heads) that closely interfaced with cardiac muscle fibers of oval nuclei(n). In panel C of the HCQ treated group (II), a dense meshwork of CD117 (+) TCs (arrows) with long and moniliform telopodes (arrow heads) are detected within sarcolemmal vacuolations (V). Inpanel D of the Zn treated group (III), a CD117 (+) network is found within the myocardium. Classic TC morphology (arrows) with spindle-shaped cells, small nucleated bodies, and very elongated and thin moniliform processes (telopodes) (arrow heads) are observed in the interstitium between spindle shaped cardiac muscle fibers with oval nuclei (n). (CD 117x400). Panel E: CD 117 (+) mast cell (MC), placed in the neighborhood of regenerated myocardial…

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  Fig. 3. panel A&B: Photomicrographs of a semi-thin section of control rat myocardium displaying standard striations of myofibrils (arrows) of oval nuclei (n) and their edges are connected with Z-lines (arrow heads). Blood vessels (bv) are evident. HCQ treated rat myocardium (group II) presenting: panel C: Curly cardiac myofibrils (arrows) with oval nuclei (n) and fragmented zones (f). Blood vessels (bv) are clearly seen. Sarcolemmal vacuoles (V) containing lipofuscin-like granules (arrow heads) are seen. panel D: Crucial zones of myofibrillar break down with focal loss of cross striations (F). Other myofibrils appear wavy and denuded (arrows). Notice congested dilated blood vessels (bv). Sarcolemmal vacuoles are clearly seen (V). elongated cells with branched extensions (arrow heads) are scattered between sarcolemmal vacuolizations. (Toluidine blue X 1000). panel E: Cardiac myofibrils (arrows) with oval nuclei (n) surrounded by clear spaces (curved arrows). Zones of myofibrillar degeneration (D) with congested blood vessels (bv) and branched TCs with intervening oval nuclei (arrow head). panel F: Irregularly arranged cardiac myofibrils (arrows) and dilated congested blood vessels (bv)…

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  Fig. 4. Electron micrographs of control cardiac myocytes from rats in group i are presented. the following details can be observed:(A) The sarcoplasm of the myofibrils exhibits a regular arrangement of myofibrils (M) with transverse striations bisected by Z-lines (arrow heads) and even rows of mitochondria (mt) surrounding the centrally located nucleus (N) with a prominent nucleolus (arrow). (TEM X6000). (B) The myofilaments are regularly arranged in sarcomeres (▬) with transverse striations (M) consisting of dark (A) and light (I) bands that intersect at Z-discs located near the steps that line up axially edge-to-edge with the intercalated disc (ID) (curved arrow). Mitochondria (mt) are present in columns parallel to the myofibrils that end at the verge of the ID. The sarcoplasmic reticulum (sr) is present between the mitochondria and ID membrane. In addition, regular myofilaments (M) connected by desmosomes (curved arrow), the cardio-myocyte nucleus (N) with extended chromatin (ch), and T-tubules (tt) can be seen. The middle line of the sarcomere (ml) is visible. (TEM X 15000). (C) The regular arrangement of myofilaments (M) bisected by Z-lines (arrowheads), blood vessel (bv), and even…

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  Fig. 5. TEM images of cardiac myocytes from the group treated with HCQ (group II) depict: (A) Irregular arrangement of myofibrils (M) in cardiac cells bisected by Z-lines (arrow heads) with localized areas of fragmentation (f) and irregular-shaped nucleus (N) with extended chromatin, surrounded by swollen mitochondria (mt). Leucocytic cellular infiltration with irregular nuclei (n) near neighboring blood vessels (bv) are visible. (TEM X6000). (B) Fragmentation (f) and damage to the regular organization of myofibrils (M) showing a bamboo-like shape with dark Z-lines between adjacent myocytes (arrow heads). The presence of vacuoles (V) and clusters of curvycircular bodies (arrows) in between the cells is noticeable. Dilated and compact mitochondria (mt) with uneven shapes and arrangement can be seen. (TEM X12000). (C) Disorganized cardiac myofibrils (M) with dark Z-lines between adjacent cells (arrow heads). Regions of degeneration (D) and unevenly arranged mitochondria (mt) of variable sizes with prominent cristae inside are visible. (TEM X12000). (D) A Tc nucleus (N) in a division state with two nucleoli (arrows) and condensed chromatin at the periphery (ch). Telopodes (double arrow)…

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  Fig. 6. The TEM micrographs from Zn-treated rat myocardium (group III) display the following: (A) Regularly arranged muscle fibers (M) with normal striations and Z-lines in between (arrow heads). The mitochondria (mt) are arranged in regularly spaced rows. The interstitium shows an elongated nucleus (N), which is most commonly a TC with peripherally condensed chromatin (ch) and a long process or telepode (curved arrow). Collagen deposition (C) is visible in the extracellular matrix between TC and cardiac myofibrils. (TEM X 6000). (B) Cardiac myocytes (M) with an oval nucleus (N) that exhibits extended chromatin. Z-lines (arrowheads) between cardio-myocyte edges and rows of oval mitochondria (mt) in between are visible. (TEM X 6000). (C) Cardiac myofibrils (M) with a regular arrangement of myofilaments linked by Z-lines (arrowheads), regular rows of mitochondria (mt) parallel to the myofibrils, and sarcoplasmic reticulum (sr) visible between mitochondria and the external lamina (arrow). (TEM X 20000). (D) Z-lines (arrowheads) between the edges of cardio myocytes (M) with regular rows of rectangular mitochondria (mt) laid in between, ending at the intercalated disc region (ID) and…

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  Fig. 7. The TEM micrographs in Fig. 7 show the effects of combined HCQ and Zn treatment on rat myocardium (group IV) as follows: (A) The image displays intact cardiac myofibrils (M) with swollen mitochondria (mt), and vacuolated sarcoplasm (V) with intact rows of intercalated discs (ID). Notice the classic Z-band (arrow heads) between cardio-myocyte edges. An elongated nucleus (N) of a TC with telopode (arrow) is visible. (TEM X 6000). (B) The micrograph exhibits a regular arrangement of myofilaments (M), some of which are vacuolated (V) connected by Z-lines (arrow heads). Integral intercalated discs of step-like design (ID) are visible. Two elongated nuclei (N) of cardiac stem cells (CSC) located in a loose extracellular matrix (ECM) with peripherally condensed chromatin (ch). The CSC of typical leptofibrils (lf) is closely supported by Tc processes (curved arrow). Extracellular collagen (C) is laid next to them. (TEM X 6000). (C) The image shows a regular arrangement of myofilaments (M) connected by Z-lines (arrow heads) and integral intercalated discs (ID) with a step-like design. Two cardiac stem cells located near a blood vessel (bv) with two large and dented nuclei, fewer dispersed…

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  Fig. 8. Histograms: 8.A. troponin (cTnI) in mg/ml. 8. B. CK-MB in U/L. 8.C. Percentage area of CD117 immuno-staining.

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  Diagram 1. The typical morphology of a telocyte (TC) with long cytoplasmic projections, or telopodes, demonstrating alternating podomers and podoms making contacts with cardiomyocytes and interstitial components (such as immune cells, blood vessels, etc.). After Klein et al. (2021).