Melatonin improves cognitive behavior, oxidative stress, and metabolism in tumor-prone lethal giant larvae mutant of Drosophila melanogaster

Arch Insect Biochem Physiol. 2021 May;107(1):e21785. doi: 10.1002/arch.21785. Epub 2021 Apr 5.

Abstract

Mutant lethal giant larvae (lgl) flies (Drosophila melanogaster) are known to develop epithelial tumors with invasive characteristics. The present study has been conducted to investigate the influence of melatonin (0.025 mM) on behavioral responses of lgl mutant flies as well as on biochemical indices (redox homeostasis, carbohydrate and lipid metabolism, transaminases, and minerals) in hemolymph, and head and intestinal tissues. Behavioral abnormalities were quantitatively observed in lgl flies but were found normalized among melatonin-treated lgl flies. Significantly decreased levels of lipid peroxidation products and antioxidants involved in redox homeostasis were observed in hemolymph and tissues of lgl flies, but had restored close to normalcy in melatonin-treated flies. Carbohydrates including glucose, trehalose, and glycogen were decreased and increased in the hemolymph and tissues of lgl and melatonin-treated lgl flies, respectively. Key enzymes of carbohydrate metabolism showed a significant increment in their levels in lgl mutants but had restored close to wild-type baseline levels in melatonin-treated flies. Variables of lipid metabolism showed significantly inverse levels in hemolymph and tissues of lgl flies, while normalization of most of these variables was observed in melatonin-treated mutants. Lipase, chitinase, transaminases, and alkaline phosphatase showed an increment in their activities and minerals exhibited decrement in lgl flies; reversal of changes was observed under melatonin treatment. The impairment of cognition, disturbance of redox homeostasis and metabolic reprogramming in lgl flies, and restoration of normalcy in all these cellular and behavioral processes indicate that melatonin could act as oncostatic and cytoprotective agents in Drosophila.

Keywords: cognition; lethal giant larvae mutant; melatonin; metabolism; redox homeostasis.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Carbohydrates / blood
  • Cognition / drug effects
  • Cryoprotective Agents / pharmacology
  • Drosophila Proteins / drug effects
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / drug effects*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Enzymes / blood
  • Homeostasis / drug effects
  • Larva / drug effects
  • Larva / genetics
  • Larva / metabolism
  • Lipids / blood
  • Melatonin / pharmacology*
  • Mutation
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Tumor Suppressor Proteins / blood
  • Tumor Suppressor Proteins / drug effects
  • Tumor Suppressor Proteins / genetics

Substances

  • Antineoplastic Agents
  • Carbohydrates
  • Cryoprotective Agents
  • Drosophila Proteins
  • Enzymes
  • Lipids
  • Tumor Suppressor Proteins
  • l(2)gl protein, Drosophila
  • Melatonin