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  • Beneficial effect of sodium thiosulfate extends beyond myocardial tissue in isoproterenol model of infarction: Implication for nootropic effects.

Beneficial effect of sodium thiosulfate extends beyond myocardial tissue in isoproterenol model of infarction: Implication for nootropic effects.

Journal of biochemical and molecular toxicology (2020-09-01)
Sriram Ravindran, Senthilkumar Gopalakrishnan, Gino A Kurian
ABSTRACT

One of the common negative impacts in the management of acute myocardial infarction is cognitive decline. Using the rat model of isoproterenol (ISO)-induced myocardial infarction, we assessed the cardioprotective effect of sodium thiosulfate (STS) and its influence on cognition. STS treatment reduced the cardiac infarct size by 75%, injury markers (lactate dehydrogenase: 60%, creatine kinase-muscle/brain: 44%) release in the blood, maintain the heart rate within a normal range (365 ± 10 bpm) and minimize postinfarction hypertrophic changes in comparison with the ISO group. At the cellular level, the heart from these rats had reduced reactive oxygen species (ROS) (25%), caspase-9 (60%), and improved mitochondrial function (restored electron transport chain function and copy number) compared to ISO hearts. The brain of STS-treated rats also showed a reduction in ROS (45%), caspase-9 (37%), and improved mitochondrial function relative to the brain of the ISO group, particularly limited to the striatum region, and these rats showed improved cognitive ability. Predominantly, the STS treatment reduced the reference memory defects observed in comparison to rats challenged by ISO. Furthermore, elevated circulating mitochondrial DNA and ATP were found in ISO-challenged rats, which indicate the cardiac mitochondria linked damage-associated patterns were restored to the sham level when pretreated with STS. We found increased H2 S, a well-known metabolite of STS with a neuroprotective role in the brain after STS administration, hinting at a possible secondary defense mechanism. In conclusion, the STS mediated cardioprotection and its nootropic effects are primarily mediated via the improvement of mitochondrial function and reduction of oxidative stress.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Isoprenaline hydrochloride
Sigma-Aldrich
2′,7′-Dichlorodihydrofluorescein diacetate, ≥97%
Sigma-Aldrich
Caspase 9 Substrate, chromogenic, ≥95% (HPLC)
Sigma-Aldrich
Caspase 3 Substrate (PKC), fluorogenic