Effect of exogenous melatonin on the ultrastructure of rat hepatocytes in experimental toxic damage

AIM: To study the effect of dark deprivation and exogenous melatonin on the ultrastructure of hepatocytes in toxic carbon tetrachloride (CCL₄) damage. METHODS: The study was conducted on male Wistar rats (n=200) at the age of 6 months, weighing 350 ± 15 g. The animals were divided into: a control group kept under a fixed light regime; a group in conditions of dark deprivation; a group in a fixed light regime, where animals received CCl4 (0.2 ml / 100 g in a mixture with olive oil 50% v/v) twice a week; a group in dark deprivation with a similar injection of CCl4 and a group in dark deprivation with exposure to CCl4 and daily intragastric administration of melatonin (Sigma-Aldrich, Inc., USA) (0.3 mg/kg). The duration of the experiment was 21 days. The ultrastructure of hepatocytes was assessed by transmission electron microscopy (TEM), and micromorphometric analysis of mitochondria (area, number, and length of crysts, concentration of mitochondrial inner membranes) was performed. Statistical processing of the results was performed in the GraphPad Prism v8.41 program (USA). RESULTS: Dark deprivation causes swelling of the cytoplasm of hepatocytes, deformation of nuclei, shedding of ribosomes with EPR, a decrease in the number of mitochondria, the length of crysts and the concentration of the inner membranes of mitochondria. Exposure to CCL₄ leads to more severe damage. In combination with dark deprivation, the toxic effect of CCL₄ is aggravated. The using of melatonin had a protective effect. CONCLUSION: Epiphyseal melatonin deficiency in dark deprivation exacerbates CCL₄ hepatotoxicity due to oxidative stress and mitochondrial dysfunction. It has been established that melatonin has a pronounced hepatoprotective effect, stabilizing the ultrastructure of hepatocytes and their energy metabolism. The use of melatonin to protect the liver in chronic intoxication and circadian disorders is promising.