Melatonin Promotes Improvement in Serum Lipid Levels and Liver Histopathology in Hyperlipidemic Rats

ABSTRACT
Hyperlipidemia or dyslipidemia is the term used for the increase in lipid levels in blood plasma, usually occurring due to a high‐fat diet associated with a sedentary lifestyle. The increase in lipid levels can cause fatty infiltration in the liver known as hepatic steatosis, which can lead to inflammation, fibrosis, and necrosis consecutively. Melatonin is the hormone primarily responsible for regulating the circadian cycle, but it has antioxidant and anti‐inflammatory properties and can also control lipid metabolism. Thus, the present research aimed to evaluate the effects of melatonin on the liver of hyperlipidemic rats. The animals were divided into control, tyloxapol, tyloxapol+melatonin. Hyperlipidemia was induced by applying tyloxapol at a dose of 400 mg/kg of body weight. Melatonin was administered simultaneously with tyloxapol in daily injections at a dose of 20 mg/kg. Sorological profiles for lipids, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase, as well as liver histopathology and immunohistochemistry, were analyzed. Treatment with melatonin demonstrated an attenuating effect on the biochemical parameters of hyperlipidemic animals, reducing on average 80% the levels of triglycerides and very‐low‐density lipoprotein when compared to the tyloxapol group after 15 days of treatment, also showing a protective effect on the hepatic parenchyma that showed no changes. In addition, the administration of melatonin reduced the expression of proinflammatory cytokines and increased the expression of anti‐inflammatory ones. The present study showed that melatonin administration has a protective effect on induction factors and the development of nonalcoholic fatty liver disease in Wistar rats with hyperlipidemia.

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Published: Apr 06, 2026
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Ana Cláudia Carvalho de Sousa