Microcystin-induced 8-hydroxydeoxyguanosine in DNA and its reduction by melatonin, vitamin C, and vitamin E in mice

Area of Science:

• Environmental toxicology
• Biochemistry
• Cellular biology

Background:

• Microcystin LR (MC-LR) is a potent liver toxin produced by Microcystis aeruginosa.
• MC-LR exposure can lead to reactive oxygen species (ROS) generation and subsequent DNA damage.
• Oxidative DNA damage, indicated by 8-hydroxydeoxyguanosine (8-OH-dG) formation, is a key mechanism of MC-LR toxicity.

Purpose of the Study:

• To investigate the efficacy of free radical scavengers in mitigating MC-LR-induced oxidative DNA damage.
• To compare the protective potential of melatonin, vitamin C (ascorbate), and vitamin E (Trolox) against MC-LR toxicity.

Main Methods:

• Quantification of 8-hydroxydeoxyguanosine (8-OH-dG) formation using High-Performance Liquid Chromatography (HPLC) with electrochemical detection.
• Assessment of the inhibitory effects of melatonin, ascorbate, and Trolox on 8-OH-dG formation in a concentration-dependent manner.
• Determination of the IC50 values for each antioxidant to quantify their efficacy in reducing DNA damage.

Main Results:

• Melatonin, vitamin C, and vitamin E all significantly inhibited MC-LR-induced 8-OH-dG formation.
• Melatonin demonstrated superior protective activity, with IC50 values substantially lower than those of ascorbate and Trolox.
• Melatonin was found to be 60-fold more effective than vitamin C and 70-fold more effective than vitamin E in preventing oxidative DNA damage.

Conclusions:

• Melatonin exhibits a potent protective effect against microcystin toxicity, primarily through its direct hydroxyl radical scavenging ability.
• Antioxidants, particularly melatonin, can effectively counteract the oxidative DNA damage induced by MC-LR.
• These findings highlight the potential therapeutic role of melatonin in mitigating cyanotoxin-induced cellular damage.