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Effects of fumarate on cardiorenal injury markers in normotensive Wistar rats

Osaze Edosuyi
Aladuna Joseph Omo-Erhabor


Fumarate, the tricarboxylic acid cycle metabolite, which evokes an antihypertensive action has been reported to exert paradoxical actions that worsen hypertension-induced organ damage. This study investigates any link between these paradoxical effects and applied doses of fumarate. Male and female Wistar rats (150-180 g) were grouped into three (3) groups containing eight (8) animals each. Group I received distilled water (3 ml/kg, po), and groups II-IV received fumarate (50, 150, and 500 mg/kg, po) respectively for 28 days. Urine was collected for 24 hours via metabolic cages on days 0 and 28. After 28 days, animals were sacrificed, and blood was collected via cardiac puncture for biochemical analyses. Fumarate exerted a dose-dependent increase in the serum levels of troponin, CK-MB, and myoglobin (p<0.001) in both male and female rats. Urine volumes were significantly reduced and peaked in rats of both sexes at 500 mg/kg of fumarate. This was followed by a simultaneous increase in sodium excretion in male rats (50.3 ± 9.3 vs 74.7 ± 4.2 mmol/L, p<0.05) at 150 mg/kg and female rats (43.3 ± 1.6 vs 89.0 ± 0.6 mmol/L, p<0.001) at 150 mg/kg. Proteinuria was only significantly elevated at 500 mg/kg in fumarate-treated male rats (92.3 ± 3.1 vs 151.5 ± 15.6 mg/24 h, p<0.05). In female rats, urinary protein excretion was increased at all doses (p<0.05). The results from this study showed that the paradoxical increase in myocardial injury is dose-dependent and occurs on sustained administration.

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eISSN: 1596-8499