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Published on: April 28, 2020
Gallic Acid and Taurine Attenuate Thiamethoxam-Induced Hepatotoxicity in Rats by Modulating SIRT-1/PGC-1α,
Sara T Elazab1, Fatmah A Safhi2, Rasha K Al-Akeel3
1Department of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
Abstract:
Background/Objectives: Thiamethoxam (TMX) is one of the most extensively utilized insecticides of the neonicotinoid family; however, its application is associated with notable toxic effects on multiple organs of mammals. Our purpose was to explore the potential hepatoprotective effect of taurine (TAU) and/or gallic acid (GA) against TMX-induced liver damage, with an emphasis on their role in regulating SIRT-1/PGC-1α, NF-κB/iNOS, and p53/Bax/caspase-3 pathways. Methods: Rats were assigned to seven groups (n = 6) and gavaged daily for 28 days with saline (control group), TAU at 50 mg/kg, GA at 20 mg/kg, TMX at 78.15 mg/kg, TMX + TAU, TMX + GA, and TMX + TAU + GA. Results: The findings revealed that TAU and/or GA attenuated TMX-induced liver injury, as demonstrated by the restoration of hepatic performance hallmarks and histological structure. TAU and GA mitigated TMX-mediated oxidative stress and boosted the antioxidant defense mechanism by upregulating the transcription levels of SIRT-1, PGC-1α, Nrf2, and HO-1. Moreover, TAU and GA suppressed TMX-associated inflammatory response by increasing IL-10 concentration and lowering the levels of NF-κB, IL-1β, and iNOS; the mRNA levels of NLRP3; and TNF-α immunoexpression. Both compounds, individually or concurrently, exerted an anti-apoptotic effect in TMX-treated rats, evidenced by increased Bcl-2 expression and reduced p53 mRNA level, Bax expression, and caspase-3 concentration. Conclusions: TAU and/or GA may be regarded as promising remedies that can alleviate TMX-induced hepatotoxicity by activating SIRT-1/PGC-1α signaling and abolishing inflammation and apoptosis.
Insights
Taurine (TAU) and gallic acid (GA) show promise in protecting the liver from thiamethoxam (TMX) insecticide damage. These compounds mitigate oxidative stress, inflammation, and apoptosis, offering potential therapeutic benefits against TMX-induced hepatotoxicity.
Area of Science:
- Toxicology
- Pharmacology
- Biochemistry
Background:
- Thiamethoxam (TMX), a widely used neonicotinoid insecticide, poses significant toxic risks to mammalian organs, particularly the liver.
- Understanding the molecular mechanisms underlying TMX-induced hepatotoxicity is crucial for developing effective countermeasures.
Purpose of the Study:
- To investigate the potential hepatoprotective effects of taurine (TAU) and gallic acid (GA) against TMX-induced liver injury in rats.
- To elucidate the roles of TAU and GA in modulating key signaling pathways, including SIRT-1/PGC-1α, NF-κB/iNOS, and p53/Bax/caspase-3.
Main Methods:
- Rats were administered TAU (50 mg/kg), GA (20 mg/kg), TMX (78.15 mg/kg), or combinations thereof daily for 28 days.
- Hepatic function, histological structure, oxidative stress markers, inflammatory mediators, and apoptosis-related proteins were assessed.
Main Results:
- TAU and/or GA significantly attenuated TMX-induced liver damage, restoring hepatic function and histological integrity.
- These compounds mitigated oxidative stress by upregulating antioxidant defenses (SIRT-1, PGC-1α, Nrf2, HO-1) and suppressed inflammation by modulating cytokine and inflammatory pathway markers (IL-10, NF-κB, IL-1β, iNOS, NLRP3, TNF-α).
- TAU and GA demonstrated anti-apoptotic effects by modulating Bcl-2, p53, Bax, and caspase-3 expression.
Conclusions:
- Taurine and gallic acid exhibit significant hepatoprotective potential against thiamethoxam-induced liver toxicity.
- Their mechanisms involve the activation of SIRT-1/PGC-1α signaling, suppression of inflammatory pathways, and reduction of apoptosis.
- TAU and GA represent promising therapeutic agents for mitigating TMX-induced hepatotoxicity.
