Rotenone impairs oxidant/antioxidant balance both in brain and intestines in zebrafish

Area of Science:

• Neuroscience
• Toxicology
• Biochemistry

Background:

• Rotenone, a pesticide inhibiting mitochondrial complex I, induces Parkinson Disease (PD)-like symptoms in rats.
• Oxidative stress, particularly reactive oxygen species (ROS) in dopaminergic (DA) neurons, is a key feature of PD.
• The gut-brain axis, linking intestinal environment to central nervous system (CNS) function, is increasingly recognized for its role in PD pathogenesis and gastrointestinal (GI) dysfunction.

Purpose of the Study:

• To investigate the mechanisms of GI dysfunction in PD by examining the oxidant-antioxidant status in the brain and intestine.
• To assess the impact of rotenone exposure on locomotor activity in zebrafish.
• To explore the gut-brain axis connection in a rotenone-induced PD model.

Main Methods:

• Adult zebrafish were exposed to 2 mg/L rotenone for 30 days.
• Locomotor activity was assessed via simple observation.
• Biochemical assays were performed to measure lipid peroxidation (LPO), nitric oxide (NO) levels, superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST) activities in brain and intestinal homogenates.

Main Results:

• Rotenone exposure led to a significant decrease in locomotor activity in zebrafish.
• Increased lipid peroxidation (LPO) was observed in both the brain and intestines.
• Nitric oxide (NO) levels increased in the brain, while GST and CAT activities decreased in both tissues. Intestinal SOD activity also decreased.

Conclusions:

• The study provides the first evidence in rotenone-exposed zebrafish supporting the gut-brain axis connection.
• Oxidative stress and altered nitric oxide levels are implicated in the observed effects.
• These findings contribute to understanding PD pathogenesis and the role of the gut-brain axis.