EFFECT OF MELATONIN ON PLASMA PYRUVATE LEVELS IN ALLOXAN-INDUCED DIABETIC RATS UNDER DIFFERENT PHOTOPERIODS
Authors: Kushnir O.Yu. , Yaremii I.M. , Kushnir O.O. , Yaremii K.M. 
Published: December 2024

Some studies suggest that melatonin exerts a stimulating effect by reducing lactate dehydrogenase activity and shifting the balance of redox enzymes towards the predominance of the Krebs cycle, thereby favoring aerobic processes that are more efficient for cellular energy production. Therefore, an in-depth investigation of this effect of melatonin is warranted. The aim of this experimental study was to examine the impact of melatonin on the levels of pyruvic acid in the plasma of rats under physiological conditions and in alloxan-induced diabetes, with a focus on hypo- and hyperfunction of the pineal gland. Methods. The study was conducted on 50 sexually mature male outbred white rats weighing 0.18–0.20 kg. Photoperiodic changes were simulated over a one-week period, with the following conditions: 1) natural light/dark cycle from March 19 to 25, 2024, averaging 12:12 hours; 2) artificial 12:12 light/dark cycle (light from 8:00 a.m. to 8:00 p.m., with illumination at 500 lux); 3) constant light (500 lux) for 24 hours; 4) constant darkness for 24 hours. Alloxan diabetes was induced by intraperitoneal injection of a 5% alloxan monohydrate solution at a dose of 170 mg/kg. Fasting glucose levels were measured using the One Touch Ultra Easy device (Johnson & Johnson, USA). The rats were divided into four groups based on lighting conditions: 1) intact rats; 2) a control group, receiving daily intraperitoneal melatonin injections (10 mg/kg) at 8 a.m. for one week (Sigma, USA); 3) rats with diabetes mellitus; 4) rats with diabetes mellitus, receiving melatonin injections (10 mg/kg) starting on the 5th day post-alloxan for one week. Animals were euthanized by decapitation under light ether anesthesia on the 12th day of the experiment. Pyruvate levels in blood plasma were measured using standard methods. Statistical analysis was performed using Statistica 10 (StatSoft Inc.). Results. It is known that the presence of hyperglycemia under the conditions of diabetes intensifies the processes of free radical oxidation. According to the data obtained by us, in diabetic rats, a high level of glucose is accompanied by an increase in pyruvate in blood serum. This happens due to dysregulation of aerobic processes in the conditions of a decrease in insulin. In this case, pyruvate turns into lactate, creating conditions for the development of lactic acidosis. Staying under conditions of dark deprivation (light 24 hours) for a week led to a 15% increase in serum glucose and pyruvate levels in blood serum compared to intact animals. A similar situation was observed in a group of diabetic animals. Under conditions of round-the-clock lighting in diabetic animals, the indicators of glucose and pyruvate content increased even in comparison with the indicators of diabetic animals under equinox conditions and were on average 22% higher. However, exposure to light deprivation (24 hours of darkness) for a week led to a 10% decrease in glucose content and a 13% increase in pyruvate content when compared to intact animals. This happens due to the activation of the processes of aerobic oxidation of glucose under the conditions of an increase in melatonin. In diabetic rats, fasting pyruvate and glucose indicators under conditions of 24-hour darkness were negated by smaller deviations when compared with a group of diabetic animals that were under conditions of the equinox. It has been established that a short daytime photoperiod (8 hours of light: 16 hours of darkness) is characterized by an increase in melatonin secretion. Under these conditions, the indicators of antioxidant protection and the immune system improved in experimental animals. In addition, pinealectomized rats are characterized by reduced activity of glutathione peroxidase in tissues due to the absence of melatonin. The introduction of melatonin led to a decrease in glucose content in diabetic rats (under conditions of darkness - to normalization). The content of pyruvate in the blood serum of diabetic animals regardless of lighting conditions under the influence of melatonin injections did not differ from the control indicators under equinox conditions. The ability of melatonin to improve glucose uptake through glucose transporters has been investigated. In addition, there are data on melatonin as an activator of pyruvate dehydrogenase. It has been realised that melatonin has possibility to inhibit the activity of pyruvate dehydrogenase kinase and activate the pyruvate dehydrogenase thereby allowing the transformation of pyruvate to acetyl-CoA and sending glucose for oxidation in the mitochondria. Conclusion. Therefore, under both normal and diabetic conditions, melatonin enhances the efficiency of aerobic glucose oxidation pathways.