# TLR2 as a Key Mediator: Bergamottin Protects Against Lead‐Induced Renal Toxicity by Modulating Oxidative Stress and Pyroptosis Pathways

## TL;DR

Bergamottin protects against lead-induced kidney damage by reducing oxidative stress and pyroptosis, with TLR2 playing a key role in this protective effect.

## Contribution

Bergamottin's protective role against lead-induced nephrotoxicity is revealed, with TLR2 identified as a key mediator.

## Key findings

- Bergamottin reduces lead-induced kidney dysfunction and oxidative stress in mice.
- Bergamottin decreases pyroptosis markers like NLRP3 and IL-18 in renal cells.
- TLR2 silencing enhances Bergamottin's protective effects, while TLR2 overexpression weakens them.

## 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.

Bergamottin protects against lead‐induced renal damage by reducing oxidative stress and pyroptosis in C57BL/6 mice. The protective effects of BGM are mediated through TLR2 modulation, as silencing TLR2 enhances its efficacy, while overexpressing TLR2 weakens its protective action in HK‐2 cells. BGM could be a potential therapeutic agent for lead‐induced nephrotoxicity.