Boron improves cardiac contractility and fibrotic remodeling following myocardial infarction injury

Abstract

Myocardial fibrosis is a major determinant of clinical outcomes in heart failure (HF) patients. It is characterized by the emergence of myofibroblasts and early activation of pro-fibrotic signaling pathways before adverse ventricular remodeling and progression of HF. Boron has been reported in recent years to augment the innate immune system and cell proliferation, which play an important role in the repair and regeneration of the injured tissue. Currently, the effect of boron on cardiac contractility and remodeling is unknown. In this study, we investigated, for the first time, the effect of boron supplementation on cardiac function, myocardial fibrosis, apoptosis and regeneration in a rat model myocardial infarction (MI)-induced HF. MI was induced in animals and borax, a sodium salt of boron, was administered for 7 days, p.o., 21 days post-injury at a dose level of 4 mg/kg body weight. Transthoracic echocardiographic analysis showed a significant improvement in systolic and diastolic functions with boron treatment compared to saline control. In addition, boron administration showed a marked reduction in myocardial fibrosis and apoptosis in the injured hearts, highlighting a protective effect of boron in the ischemic heart. Interestingly, we observed a tenfold increase of nuclei in thin myocardial sections stained positive for the cell cycle marker Ki67 in the MI boron-treated rats compared to saline, indicative of increased cardiomyocyte cell cycle activity in MI hearts, highlighting its potential role in regeneration post-injury. We similarly observed increased Ki67 and BrdU staining in cultured fresh neonatal rat ventricular cardiomyocytes. Collectively, the results show that boron positively impacted MI-induced HF and attenuated cardiac fibrosis and apoptosis, two prominent features of HF. Importantly, boron has the potential to induce cardiomyocyte cell cycle entry and potentially cardiac tissue regeneration after injury. Boron might be beneficial as a supplement in MI and may be a good candidate substance for anti-fibrosis approach.

Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention

“…An increasing number of new pharmaceutical targets have been developed, such as a soluble epoxide hydrolase vaccine, which improves cardiac function, and boron, as well as a new ligand of the apelin peptide jejunum receptor apela, which reduce myocardial fibrosis and apoptosis ( Bouchareb et al, 2020 ; Pan et al, 2020 ; Kitsuka et al, 2022 ). There are also interventions targeting inflammation response, for instance, the inhibition of coagulation protein tissue factor cytoplasmic domain improves cardiac remodeling by regulating inflammation and angiogenesis ( Chong et al, 2021 ).…”

4 hidroksi fenilboronik asidin lipopolisakkarit ile indüklenmiş karaciğer hasarı üzerine muhtemel koruyucu etkilerinin incelenmesi

“…Bor ile ilgili yapılan çalışmalar incelendiğinde, bor ve bor bileşiklerinin kemik sağlığı üzerine ve kırık iyileşmesi üzerine olumlu etkileri olduğu; yara iyileşmesi üzerine olumlu etkileri olduğu, kanser tedavisinde kullanıldığı, immüniteyi destekleyici etkileri olduğu, kardiyovasküler sağlık üzerine olumlu etkileri olduğu ve anti enflamatuvar etkisi olduğu görülmüştür [7][8][9][10][11][12]. Borik asit veya borat olarak borun cis-hidroksil grupları, özellikle riboz içeren biyolojik olarak önemli birkaç şekerle ester kompleksleri oluşturur.…”

The Rise of Boron-Containing Compounds: Advancements in Synthesis, Medicinal Chemistry, and Emerging Pharmacology

“…However, the essentiality of boron in supporting animal life is substantiated by the detrimental effects of boron deficiency, such as impeding embryo development, − pulmonary fibrosis, osteoporosis, − cognitive function, , calcium and magnesium concentration, − and steroid hormone concentration. , As boric acid and borates enter animal/human cells, they interact with and often disrupt the kinetics and dynamics of other biomolecules containing cis -diols, such as flavin adenine dinucleotide, nicotinamide adenine dinucleotide (NAD), ribonucleic acids, ribonuclease, and S-adenosyl methionine (SAM). , Although disruptive in certain cases, supplementation with boric acid in humans at doses of 20–60 mg/day has been effective for the treatment of arthritis, certain types of neoplasia, − heart function, and metabolic disorders. , Additionally, boron supplementation has several medical applications, such as in aging, , improving bone health, , improving cardiac health after myocardial infarction, antiseptic, antibiotic, and hormone regulation. ,− Similarly, fructoborate ( 2 ), a naturally occurring borate ester, acts as an antioxidant and anti-inflammatory agent that likely affects treatment of knee/joint function, osteoporosis, osteoarthritis, ,− cancer, ,, and/or cognitive health. , Thus, naturally occurring boron-containing compounds (BCC) warrant further exploration as mechanistic insight into the role of boron in animal health will guide the design of novel therapeutics.…”

“…58,59 Although disruptive in certain cases, supplementation with boric acid in humans at doses of 20−60 mg/day has been effective for the treatment of arthritis, certain types of neoplasia, 60−62 heart function, and metabolic disorders. 63,64 Additionally, boron supplementation has several medical applications, such as in aging, 58,65 improving bone health, 66,67 improving cardiac health after myocardial infarction, 68 antiseptic, 69 antibiotic, 70 and hormone regulation. 56,71−73 Similarly, fructoborate (2), a naturally occurring borate ester, acts as an antioxidant 74 and antiinflammatory agent that likely affects treatment of knee/joint function, osteoporosis, osteoarthritis, 73,75−77 cancer, 60,78,79 and/or cognitive health.…”