Tamara M Mladenović, Sanja Lj Matić
Forskolin and pinitol are bioactive dietary compounds studied for several pharmacological properties. Considering their widespread therapeutic application and the limited information available regarding their genotoxic and/or antigenotoxic properties, the present study investigated whether commercially available forskolin and pinitol can induce DNA damage and/or protect DNA against damage induced by ethyl methanesulfonate (EMS). The sex-linked recessive lethal (SLRL) test in germline and the alkaline comet assay in somatic cells were performed in Drosophila melanogaster to assess in vivo genotoxicity and DNA-protective effects against EMS-induced DNA damage. The SLRL assay demonstrated that neither forskolin nor pinitol induced genotoxic effects in D. melanogaster males. Both compounds significantly reduced EMS-induced sex-linked recessive lethal mutations, indicating a marked DNA-protective effect in germline cells. In the comet assay, no significant increase in DNA damage was observed following forskolin treatment, whereas pinitol induced moderate increases in the total comet score only at the highest concentration compared with the negative control, with values statistically significantly lower than those of the positive control. The greatest DNA-protective effect against EMS was observed following co-treatment with 0.5 mg/mL of forskolin or pinitol, resulting in percentage reductions of 94.2% and 80.5%, respectively. The findings suggest that forskolin and pinitol possess protective effects against EMS-induced DNA damage. Their DNA-protective capacity at non-genotoxic concentrations indicates potential chemopreventive properties and supports further investigation of their biological effects. These findings support further investigation into the molecular mechanisms underlying their protective effects and their potential application in the prevention and management of diseases associated with genomic instability.