Studies on the role of zinc in maintaining antioxidant status in the heart.

Okafor, Oronne Anyahuru Gillian

Abstract

Zinc (Zn2+) is an essential micronutrient which plays a pivotal role as a signalling, catalytic and structural component in cells and functions in several physiological processes such as immune function, wound healing, cognition, reproduction and as co-factor for various enzymes involved in antioxidant system of the body. It functions as a component of the antioxidant defence system within tissues and cells, and has been identified as a factor of great significance in cardiovascular health. Obesity is a major risk factor for cardiovascular disease. It is thought that an abnormality in adipocyte Zn2+ transport may contribute to obesity development. Hypozincaemia (low Zn2+ level in blood) in an obese person is followed by a decrease in the systemic antioxidant status resulting in a reduced response to oxidative stress, while Zn2+ supplementation reduces inflammation caused by obesity. The connection between obesity and the outcome from an acute myocardial infarction (AMI) is many-sided. Both obesity and AMI have been associated with production of inflammatory mediators and reactive oxygen species (ROS), which cause cell injury and eventually cell death. The pro-inflammatory and pro-oxidant status associated with obesity in the presence of an AMI may therefore present an increased risk of morbidity and mortality. The present study aimed to investigate the role of Zn2+ in maintaining antioxidant status in the heart of both obese and non-obese settings. Results from biochemical assays showed that chronic exposure of mice to a suboptimal level (5mg/kg) of dietary Zn2+ in combination with a high fat diet did not significantly alter cardiac levels of glutathione (GSH), compared with the Zn2+ adequate group (Zn2+ 35 mg/kg) at 15 and 25 weeks. However, the level of total GSH in the heart was significantly reduced by approximately 50% in the Zn2+ adequate group at 25 compared with 15 weeks. A suboptimal level of Zn2+ (5 mg/kg) did not significantly affect Copper Zinc superoxide dismutase (Cu/Zn-SOD) activity after either 15 or 25 weeks of dietary intervention. However, heart Cu/Zn-SOD activity was higher in all the groups at 25 compared to 15 weeks. In a second study in rats subjected to in vitro myocardial I/R injury, 2 weeks of severe dietary Zn2+ depletion ( < 1 mg Zn/kg diet) was associated with reduced cardiac GSH levels, while Cu/Zn-SOD activity was not affected by dietary Zn2+ intake. In contrast, in vitro acute Zn2+ depletion with TPEN reduced Cu/Zn-SOD activity, but not GSH content. Neither method of Zn2+ depletion had any effect on either myocardial Zn2+ content or Caspase 3 activity, but plasma levels of Zn2+ were reduced following dietary Zn2+ depletion. These results demonstrate that Zn2+ depletion results in a worse outcome from I/R via different mechanisms, depending upon the method used to deplete ZN2+. and shows the protective effect of Zn2+ as a co-factor of antioxidant enzymes in preventing injuries caused by I/R and propose its use as a possible treatment against cardiovascular disease. Further studies are required to better understand the effect of acute or chronic Zn2+ depletion on biomarkers of antioxidant status in the heart.

Citation

OKAFOR, O.A.G. 2020. Studies on the role of zinc in maintaining antioxidant status in the heart. Robert Gordon University, MRes thesis. Hosted on OpenAIR [online]. Available from: https://openair.rgu.ac.uk

• Thesis Type: Thesis
• Deposit Date: Mar 2, 2021
• Publicly Available Date: Mar 2, 2021
• Keywords: Obesity; Zinc; Zinc depletion; Heart; Cardiovascular system; Cardiovascular disease
• Public URL: https://rgu-repository.worktribe.com/output/1239207
• Award Date: Apr 30, 2020