Melatonin improved rat cardiac mitochondria and survival rate in septic heart injury

Abstract

The pathogenesis of septic myocardial depression is complicated. Mitochondrial dysfunction has been suggested to be one of the main reasons for the reduced cardiac function. As melatonin is an antioxidant with the potential to scavenge radicals in mitochondria, we therefore employed a sepsis model, that is, cecal ligation and double puncture (CLP) in rats, to study the melatonin effects on: (i), myocardial mitochondrial function; (ii), heart systolic function; and (iii), prognosis of septic rats. We demonstrate that melatonin treatment (30 mg/kg, 3, 6, 12, 18, 24 hr after CLP) (i) improved myocardial cytochrome c oxidase (CcOX) activity and blood lactate level, (ii) attenuated heart dysfunction with a higher left ventricular ejection fraction (EF), and (iii) promoted 48-h survival of the rats compared to CLP animals with no melatonin treatment. In conclusion, our results show that rat myocardial mitochondrial CcOX activity was depressed during severe sepsis accompanied by myocardial depression characterized by the decline of EF. In septic rats, melatonin increased the CcOX activity, improved heart systolic function, and lowered mortality rate. The clinical use of melatonin in septic myocardial depression should be tested in the future.

Action of Melatonin on Severe Acute Liver Failure in Rats

“…Similar results were previously reported in the literature using MLT in the treatment of different induced pathological conditions in animal models, such as sepsis [30][31], Alzheimer [32], and liver injury caused by cholangiocarcinoma [33]. Table 2 shows the result for enzyme concentrations associated with liver damage in the 24-hour experiment.…”

Melatonin Receptors Mediate Improvements of Survival in a Model of Polymicrobial Sepsis

“…In the past, three investigators have independently demonstrated significant improvements of survival after administration of 5-20 mg/kg melatonin after LPS-induced sepsis in mice and rats (5,8,10). Using the model of cecal ligation and puncture in rats and mice, a number of researchers were able to demonstrate the beneficial effects of melatonin treatment with respect to skeletal (15,16) or cardiac (17,31,32) mitochondrial dysfunction, as well as regarding survival (9,32), using between 3 and 30 mg/kg melatonin. Further, previous studies on organ protective effects of melatonin after different models of stress show comparable beneficial results for doses between 100 µg/kg and 100 mg/kg melatonin (33).…”

Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition

“…The chemical structure of melatonin has remained very stable for billions of years, and its structure is identical from cyanobacteria to human beings 25, 26, 27. In recent years, a vast number of studies have documented the involvement of melatonin in cardiac protection 28, 29, 30, 31, 32, 33. Melatonin presumably enters mitochondria through oligopeptide transporters 34.…”