Xanthine Oxidase Inhibitor, Allopurinol, Prevented Oxidative Stress, Fibrosis, and Myocardial Damage in Isoproterenol Induced Aged Rats

Md Abu Taher Sagor, Nabila Tabassum, Md Abdullah Potol, Md Ashraful Alam, Md Abu Taher Sagor, Nabila Tabassum, Md Abdullah Potol, Md Ashraful Alam

Abstract

We evaluated the preventive effect of allopurinol on isoproterenol (ISO) induced myocardial infarction in aged rats. Twelve- to fourteen-month-old male Long Evans rats were divided into three groups: control, ISO, and ISO + allopurinol. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers analyses. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Our investigation revealed that the levels of oxidative stress markers were significantly increased while the level of cellular antioxidants, catalase activity, and glutathione concentration in ISO induced rats decreased. Treatment with allopurinol to ISO induced rats prevented the elevated activities of AST, ALT, and ALP enzymes, and the levels of lipid peroxidation products and increased reduced glutathione concentration. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys. Furthermore, allopurinol treatment prevented the inflammatory cells infiltration and fibrosis in ISO induced rats. In conclusion, the results of our study suggest that allopurinol treatment is capable of protecting heart of ISO induced myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis.

Figures

Figure 1
Figure 1
Hematoxylin and Eosin staining showed inflammatory cell infiltration and necrosis in left ventricle of heart section of rats treated with ISO. Control rats showed normal architecture with very well-shaped cardiomyocytes in left ventricle of heart (a). ISO treatment increased necrosis to cardiomyocytes and the mononuclear inflammatory cells infiltration in left ventricle of heart (b) which was normalized by allopurinol treatment (c). Moreover control rats showed normal baseline collagen around cardiomyocytes (a) which was significantly increased in ISO treated rats (b). Allopurinol treatment further prevented the fibrosis in heart of ISO treated rats. Sirius red staining showed fibrosis (red color) in left ventricle of heart section of rats treated with ISO. (a, d) Control; (b, e) ISO; and (c, f) ISO + allopurinol, magnification 40x.
Figure 2
Figure 2
Control rats showed low amount of mast cells in LV of heart (a). However, ISO administration increased degranulated mast cell infiltration in LV of heart which was significantly reduced in allopurinol treated rats. Toluidine blue staining showed mast cells infiltration (deep blue dots) in heart of rats treated with ISO. (a) Control; (b), ISO; (c) ISO + allopurinol, magnification 40x.
Figure 3
Figure 3
Hematoxylin and Sosin staining showed inflammatory cell infiltration and necrosis in kidney section of rats treated with ISO. Sirius red staining showed fibrosis (red color) in kidney section of rats treated with ISO. (a, d) Control; (b, e) ISO; and (c, f) ISO + allopurinol, magnification 40x.
Figure 4
Figure 4
Prussian blue staining showed iron deposition in heart and kidney section of rats treated with ISO and allopurinol. (a, d) Control; (b, e) ISO; and (c, f) ISO + allopurinol, magnification 40x.

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