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

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.

Label‐free quantitative mass spectrometry analysis of the circadian proteome of Drosophila melanogaster lethal giant larvae mutants reveals potential therapeutic effects of melatonin

“…Excessive levels of free radicals frequently lead to the development of oxidative stress, thus causing oxidative damage to major organelles in the (human) body (Bhatti et al, 2017). This certainly is in support of the previously mentioned finding that demonstrated decreased antioxidant enzymes activity in the head tissues of lgl mutants because of their increased utilization to prevent free radical‐induced damages (Wong et al, 2021).…”

“…Aside from that, peroxisome is also an important organelle that is involved in the reactive oxygen species metabolism (Lodhi & Semenkovich, 2014). The reduction in the expression of peroxisome‐related proteins (antioxidant enzymes: catalase and superoxide dismutase [Cu‐Zn]) in the intestinal tissues of lgl mutants was consistent with the reduced levels of antioxidant activities as previously reported (Wong et al, 2021). While proteins involved in the longevity regulating pathway—multiple species are generally correlated with increased lifespan in model organisms (e.g., yeast, worms, and flies) (Anisimova et al, 2018; Sørensen & Loeschcke, 2002).…”

“…Melatonin (0.025 mM) was incorporated into the diet medium and fed to the adult male flies for anticancer treatment (melatonin‐treated lgl mutant flies). The selection of melatonin concentration was determined based on the optimal concentrations and safety assessment reported in several previous studies (Bonilla et al, 2002; Coto‐Montes & Hardeland, 1999; Jones et al, 2015; Medina‐Leendertz et al, 2014; Vasuki et al, 2016; Wong et al, 2021). Mutant flies were fed with melatonin‐treated diet medium (melatonin‐treated lgl mutant flies) for 10 days and consecutively collected on the 11th day.…”

Alpha‐ketoglutarate supplementation in long‐lived Drosophila melanogaster: Impact on lifespan and metabolic responses

“…Glutathione‐ S ‐transferase (GST) was shown to be suppressed by preparations of chili pepper that extended lifespan in D. melanogaster (Semaniuk et al, 2022a, 2022b). It was also shown that different isoenzymes of GST can be differentially regulated and affected by circadian rhythms (Wong et al, 2023).…”

Protective Influence of Fisetin on Cognitive and Biochemical Indices in N-Nitrosodietyhlamine Treated Drosophila Melanogaster

“…Cancer and oxidative stress institute a vicious cycle; when oxidative stress surpasses the capability of the oxidation-reduction system of the body, gene mutations could result and intracellular signal transduction and transcription factors could be affected directly or through antioxidants, leading to carcinogenesis [20]. The tumour-bearing state is under oxidative stress tightly linked with active oxygen synthesis by tumour cells and irregular oxidation-reduction regulation [21]. Though tumour bearing tissues bear reduced free radical load due to uncontrolled and higher number of cell division, the oxidative stress is elevated [22] systemically in the tumor-bearing host.…”