Nattokinase Mitigates Myocardial Damage and Renal Dysfunction in γ-Irradiated Rats Treated with Isoproterenol

Background: Acute myocardial necrosis, or myocardial infarction (MI), is the most deadly form of coronary artery disease (CAD), which typically occurs when blood flow to a portion of the heart stops, damaging the heart muscles. The synthetic nonselective β-adrenergic agonist isoproterenol is known to cause cardiac conditions like energy depletion, coronary hypotension, myocardial oxidative stress, and calcium overload. Hemorrhoids, diabetes, muscle spasms, chronic inflammation, cardiovascular disorders, Alzheimer's disease, stroke, and other conditions can all be treated with nattokinase (N.K). Radiation-induced heart disease (RIHD) syndrome, which includes pericarditis, cardiomyopathy, coronary artery disease, valvular heart disease, and cardiac conduction abnormality, is caused by radiation exposure to the heart cells. The present study aims to investigate the effectiveness of nattokinase against myocardial infarction caused by ISO injection in rats undergoing whole-body fractionated gamma irradiation. Methods: Rats received an oral aqueous suspension of N.K. (720 FU/kg body weight/day) for ten days with exposure to 5 Gy of fractionated gamma radiation (0.5 Gy per day; for ten consecutive days (dose rate 0.401 Gy/min), while ISO was injected subcutaneously to rats (at a dose of 150 mg/kg body weight/day for two consecutive days starting on the first day of the experiment). Results: obtained data showed that the concentration of ANP (29.49%), TROPONIN (29.37%), GSH (35.63%), MDA (23.5%), TNFα (28.29%), and Enos (51.02%) contents in the heart, were significantly improved in groups of rats that received N.K along with ISO and γ-radaition compared to the group received ISO and γ-rays. In addition, indicators of renal status include NGAL (35.58%), ALDOSTERONE (43.93%), ANG-II (28.57%), and eNOS (39.27%), besides KIM-1 (38.97%), GSH (26.09%), MDA (59.49%), and TNF-α (17.82%) in kidney tissue are significantly improved. Moreover, the serum inflammatory index IL-18 (29.45%) and the organ damage index LDH (69.4%) in Serum were modified. In conclusion, N.K., with its antioxidant and anti-inflammatory capabilities, preserves the myocardium from disruption of blood flow processes resulting from increased oxidative burden after injection of Isoproterenol or exposure to radiation, through multiple routes of action, including activation of heart (ANP/cTnI/GSH-H/MDA/TNF-α/), stimulation of kidney (KIM-1/ANG-II/aldosterone/NGAL), activation of Serum IL-18/LDH and suppression of heart and kidney ENOS.