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TLR2 as a Key Mediator: Bergamottin Protects Against Lead-Induced Renal Toxicity by Modulating Oxidative Stress and
Yanping Zhu1, Kaisheng Zhang2, Song Wen3
1Department of Urology Surgery The First Affiliated Hospital, and the College of Clinical Medicine of Henan University of Science and Technology Luoyang China.
Abstract:
Lead (Pb) toxicity is a major health concern, with the kidney being one of the primary target organs. Current therapeutic strategies for Pb-induced nephrotoxicity are limited, highlighting the need for effective protective agents. Bergamottin (BGM), a natural furanocoumarin, has been reported to possess antioxidant and anti-inflammatory properties, but its role in Pb-induced renal injury has not been elucidated. In this study, we investigated the protective effects of BGM against Pb-induced nephrotoxicity and explored the underlying mechanisms. BGM treatment notably mitigated Pb-induced renal dysfunction, evidenced by significant reductions in serum creatinine and BUN levels. It also effectively ameliorated oxidative stress by reducing MDA and increasing antioxidant enzyme activities. BGM treatment also decreased the expression of NLRP3, caspase-1, and IL-18, thus alleviating pyroptosis-induced renal injury. Moreover, we found that TLR2 is the key factor; silencing TLR2 enhanced BGM's efficacy in protecting against Pb-induced renal damage, while overexpressing TLR2 attenuated BGM's protective benefits in HK-2 cells, highlighting the crucial role of TLR2 in mediating BGM's effects. These findings indicate that BGM could serve as a potential therapeutic agent for Pb-induced nephrotoxicity, with its protective effects primarily mediated through modulation of TLR2 and subsequent reduction in oxidative stress and pyroptosis.
Insights
Bergamottin (BGM) protects kidneys from lead toxicity by reducing oxidative stress and pyroptosis. Its therapeutic effects are mediated through Toll-like receptor 2 (TLR2) modulation, offering a potential treatment for lead-induced nephrotoxicity.
Area of Science:
- Toxicology
- Nephrology
- Pharmacology
Background:
- Lead (Pb) toxicity poses significant health risks, particularly targeting the kidneys.
- Existing treatments for lead-induced nephrotoxicity are insufficient, necessitating novel therapeutic approaches.
Purpose of the Study:
- To investigate the protective effects of Bergamottin (BGM) against lead-induced kidney damage.
- To elucidate the underlying mechanisms of BGM's renoprotective action, focusing on oxidative stress, pyroptosis, and Toll-like receptor 2 (TLR2).
Main Methods:
- Assessed BGM's impact on lead-induced renal dysfunction markers (serum creatinine, BUN).
- Evaluated BGM's effects on oxidative stress indicators (MDA, antioxidant enzymes).
- Examined the role of TLR2 by using gene silencing and overexpression in HK-2 cells to understand its mediation of BGM's protective effects against lead toxicity.
Main Results:
- BGM treatment significantly reduced markers of renal dysfunction and oxidative stress caused by lead exposure.
- BGM administration decreased the expression of NLRP3, caspase-1, and IL-18, mitigating pyroptosis.
- TLR2 was identified as a key mediator; its silencing enhanced BGM's protective effects, while overexpression attenuated them.
Conclusions:
- Bergamottin demonstrates significant potential as a therapeutic agent for mitigating lead-induced nephrotoxicity.
- BGM's protective mechanisms involve the modulation of TLR2, leading to reduced oxidative stress and pyroptosis in the kidney.
