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Published on: February 9, 2016
Rifaximin Protects against Malathion-Induced Rat Testicular Toxicity: A Possible Clue on Modulating Gut Microbiome
Nesreen Nabil Omar1, Rasha A Mosbah2, Wedad S Sarawi3
1Department of Biochemistry, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 11585, Egypt.
Abstract:
Testicular dysfunction is caused by chronic exposure to environmental pollution, such as malathion, which causes oxidative stress, promoting cell damage. Autophagy is a key cellular process for eliminating malfunctioning organelles, such as the mitochondria (mitophagy), an eminent source of reactive oxygen species (ROS). Autophagy is crucial for protection against testicular damage. Rifaximin (RFX) is a non-absorbable antibiotic that can reshape the gut microbiome, making it effective in different gastrointestinal disorders. Interestingly, the gut microbiome produces short chain fatty acids (SCFAs) in the circulation, which act as signal molecules to regulate the autophagy. In this study, we investigated the regulatory effects of RFX on gut microbiota and its circulating metabolites SCFA and linked them with the autophagy in testicular tissues in response to malathion administration. Moreover, we divided the groups of rats that used malathion and RFX into a two-week group to investigate the mitophagy process and a four-week group to study mitochondriogenesis. The current study revealed that after two weeks of cotreatment with RFX, apoptosis was inhibited, oxidative stress was improved, and autophagy was induced. More specifically, PINK1 was overexpressed, identifying mitophagy activation. After four weeks of cotreatment with RFX, there was an increase in acetate and propionate-producing microflora, as well as the circulating levels of SCFAs. In accordance with this, the expression of PGC-1α, a downstream to SCFAs action on their receptors, was activated. PGC-1α is an upstream activator of mitophagy and mitochondriogenesis. In this sense, the protein expression of TFAM, which regulates the mitochondrial genome, was upregulated along with a significant decrease in apoptosis and oxidative stress. Conclusion: we found that RFX has a positive regulatory effect on mitophagy and mitochondria biogenesis, which could explain the novel role played by RFX in preventing the adverse effects of malathion on testicular tissue.
Insights
Rifaximin (RFX) protects testicular tissue from malathion-induced damage by enhancing autophagy and mitochondrial repair. This involves regulating gut microbiota, boosting beneficial short-chain fatty acids (SCFAs), and promoting mitophagy and mitochondriogenesis.
Area of Science:
- Environmental toxicology
- Cellular biology
- Microbiome research
Background:
- Chronic exposure to environmental pollutants like malathion induces testicular dysfunction via oxidative stress and cell damage.
- Autophagy, particularly mitophagy, is vital for removing damaged mitochondria and protecting testicular tissue.
- Rifaximin (RFX), an antibiotic, modulates gut microbiota, influencing circulating short-chain fatty acids (SCFAs) that regulate cellular processes.
Purpose of the Study:
- To investigate the regulatory effects of Rifaximin (RFX) on gut microbiota and circulating SCFAs.
- To link RFX-induced gut microbiome changes to autophagy modulation in testicular tissue.
- To evaluate RFX's impact on mitophagy and mitochondriogenesis in response to malathion exposure.
Main Methods:
- Rats were exposed to malathion and treated with RFX for two and four weeks.
- Mitophagy activation was assessed by PINK1 overexpression.
- Mitochondrial biogenesis was evaluated by PGC-1α and TFAM expression, alongside SCFA analysis.
Main Results:
- RFX treatment inhibited apoptosis, reduced oxidative stress, and induced autophagy, evidenced by PINK1 upregulation after two weeks.
- After four weeks, RFX increased acetate and propionate-producing bacteria and circulating SCFAs.
- RFX activated PGC-1α and upregulated TFAM, promoting mitochondrial biogenesis and further reducing damage.
Conclusions:
- RFX positively regulates mitophagy and mitochondrial biogenesis.
- RFX's beneficial effects on testicular tissue against malathion toxicity are mediated through gut microbiota and SCFA production.
- RFX represents a potential therapeutic strategy for mitigating environmental pollution-induced testicular damage.
