Endocannabinoid system modulation by CB2 receptor agonists as a remediation strategy for mercury-induced toxicity in the Neotropical fish piau (Leporinus friderici)

• Grant number: 25/12723-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2025
• End date: March 31, 2029
• Field of knowledge: Biological Sciences - Ecology
• Principal Investigator: Diana Amaral Monteiro
• Grantee: Yan Costa Gonçalves
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Amazonian fish farming, essential for food security and the regional economy, is continuously challenged by mercury (Hg) contamination, a persistent pollutant that has compromised local ecosystems for decades and poses a threat to multiple socio-environmental dimensions. Studies have reported the presence of Hg in the tissues of Leporinus friderici (commonly known as piau), a fish species widely consumed in the region; however, the sublethal effects of this contamination on its physiological systems, as well as potential mitigation strategies, remain unexplored. In this context, the type 2 cannabinoid receptor (CB2r) has been highlighted for its role in modulating antioxidant and cardioprotective responses in fish, suggesting a potential function in reducing metal-induced toxicity. Among the natural agonists of CB2r, curcumin, a polyphenol derived from Curcuma longa, has emerged as a promising compound, recognized for its ability to decrease both Hg toxicity and accumulation in aquatic organisms. Therefore, this project aims to evaluate the effects of acute exposure (24h) to HgCl¿ (0.5 mg kg¿¹) in L. friderici, by analyzing multiple biomarkers under the following conditions: (I) physiological baseline; (II) after CB2r activation using a synthetic and a natural agonist (HU-308 and curcumin, respectively); (III) after CB2r inhibition using a selective antagonist (SR 144528); and (IV) after CB2r inhibition followed by curcumin treatment. Biomarkers to be assessed include biometric parameters (hepatosomatic index and relative ventricular mass); physiological parameters (in situ heart rate, ventricular contractility, and intracellular signaling pathways in cardiomyocytes); molecular markers (expression of calcium-handling proteins and transcription factors related to antioxidant components in cardiac tissue); biochemical markers (enzymatic and non-enzymatic components of the antioxidant system and oxidative stress markers) in the ventricle, liver, and white muscle; neurotoxic markers (in brain and white muscle); and mutagenic markers (in erythrocytes) of L. friderici. The results will elucidate the mechanisms of Hg toxicity in L. friderici, assessing its ecological impact in Amazonian ecosystems. CB2r activation may reduce Hg bioaccumulation and tissue damage, revealing cellular protective pathways. Furthermore, confirming curcumin as a phyto-agonist of CB2r would reinforce its therapeutic potential against Hg toxicity in aquatic organisms, supporting sustainable management strategies in aquaculture and enhancing food safety in national fish farming practices. (AU)