A combination of dimethyl sulfoxide ( DMSO ) and methyl paraben ( nipagin ) in Drosophila food affects survival rate

Huntington’s disease (HD) is a dominant, late-onset neurodegenerative disease caused by an expansion of a homopolymeric polyglutamine (polyQ) tract within the disease-specific huntingtin (Htt) protein (The Huntington’s Disease Collaborative Research Group). HD portrays a clinical condition, which is characterised by the selective and progressive loss of neurons, eventually leading to cognitive, behavioral, and physical defects that can ultimately cause the death of the diseased individual (Beal et al., 2005). At present, there is no cure or effective therapeutic strategy for HD or other neurodegenerative diseases. Administration of plant-derived compounds or ‘phytochemicals’ that can target multiple cellular functions and processes are anticipated to achieve better therapeutic efficacy with minimal or no side effects as opposed to mono-targeted agents or synthetic drugs in the treatment of multi-faceted neurodegenerative diseases. In our attempt to test the efficacy of phytochemicals in alleviating disease symptoms, we performed pilot experiments using a Drosophila model of Huntington’s disease to investigate if both dimethyl sulfoxide [(CH3)2S; DMSO] and methyl paraben (HOC6H4CO2CH3; nipagin) at intended concentrations can be administered without any undesirable effects. DMSO is an organosulfur, polar, aprotic compound, which is commonly used as a solvent for the dissolution of a wide range of polar and nonpolar molecules (Szmant, 1975). DMSO has the unique capability to penetrate living tissues without causing significant damage. Due to its broad solubilising property, DMSO is used as a solvent for many drug molecules and is also employed as the vehicle control-of-choice for both in vitro and in vivo studies. The phytochemical we wanted to test was dissolved in DMSO which was thoroughly mixed with regular Drosophila food containing nipagin also. Nipagin is one of the member of family of parabens (methyl, ethyl, butyl, heptyl, and benzyl parabens) and is commonly used in Drosophila food as an anti-microbial agent. Parabens are particularly active against bacteria, yeast and moulds. Their key mechanisms of action include inhibition of membrane transport and mitochondrial function. It has been reported that increasing doses of DMSO exhibit toxicity above which survival is reduced (Agrawal et al., 2005). However, we observed that a safe dose of DMSO in combination with nipagin is toxic as revealed by significantly reduced eclosion rate of wild type flies (Canton S). Similar results were observed in our experiments in which the control male flies not expressing mHtt (internal control) and female flies expressing the mutant protein also displayed reduced survival. In order to check the reason for the reduced eclosion, we conducted a series of experiments and found that safe dose of DMSO alone did not affect the survival rate of the flies but if added along with the safe dose of nipagin then it resulted in significant reduction in eclosion rate. Although DMSO is an excellent solvent for a wide variety of drugs employed in biomedical research, caution is required when added with food ingredients of Drosophila while designing and interpreting experiments.