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<p>Benzo[a]pyrene (B[a]P) is a typical environmental persistent organic pollutant and a known nephrotoxicant. However, its toxicological profile under short-term, high-dose exposure conditions remains incompletely characterized. To address this, we established a C57BL/6J mouse model in which a single oral dose of 50&#xa0;mg/kg B[a]P was administered. The results showed that time-dependent renal injury following Bla]P exposure. Within 3 days serum creatinine (Scr) and blood urea nitrogen (BUN) levels increased significantly (<i>P</i> &lt; 0.05), coinciding with elevated renal malondialdehyde (MDA) content. Concurrently, superoxide dismutase (SOD) and catalase (CAT) activities, as well as total antioxidant capacity (T-AOC) were markedly reduced (<i>P</i> &lt; 0.05). By days 7–14 days, the pathological changes shifted to inflammation and apoptosis, evidenced by upregulated TNF-α, IL-6, and caspase-3 at both gene and protein levels, alongside elevated nitric oxide synthase (NOS) and lactate dehydrogenase (LDH) activities (<i>P</i> &lt; 0.05). While the Rictor/mTORC2 pathway regulates renal pathology, its role in B[a]P-induced injury remains unelucidated. Our study found that B[a]P exposure (7–14 days) significantly upregulated key components of and its downstream effectors (AKT1 and PKC-ζ) at both transcriptional levels (<i>P</i> &lt; 0.05). Mechanistic studies in macrophage-specific Rictor knockout mice (Mac Rictor-/-) showed that, inhibiting Rictor/mTORC2 suppressed B[a]P-induced renal oxidative stress, inflammatory factor release, and apoptosis. This study first revealed that the Rictor/mTORC2 pathway serves as a potential molecular therapeutic target for B[a]P-induced kidney injury.</p>

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Rictor/mTORC2 signaling pathway mediates Benzo[a]pyrene-induced renal injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月24日

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  • Jian-Qiu Han,
  • Ying Qu,
  • Yuan-rong Zhu,
  • Ya-Lei Qi,
  • Teng-Fei Liu,
  • Yong-Mei Li,
  • Yan-Jia Zhang,
  • Juan Tan,
  • Hong-hui Han,
  • Xue-Yun Ma

摘要

Benzo[a]pyrene (B[a]P) is a typical environmental persistent organic pollutant and a known nephrotoxicant. However, its toxicological profile under short-term, high-dose exposure conditions remains incompletely characterized. To address this, we established a C57BL/6J mouse model in which a single oral dose of 50 mg/kg B[a]P was administered. The results showed that time-dependent renal injury following Bla]P exposure. Within 3 days serum creatinine (Scr) and blood urea nitrogen (BUN) levels increased significantly (P < 0.05), coinciding with elevated renal malondialdehyde (MDA) content. Concurrently, superoxide dismutase (SOD) and catalase (CAT) activities, as well as total antioxidant capacity (T-AOC) were markedly reduced (P < 0.05). By days 7–14 days, the pathological changes shifted to inflammation and apoptosis, evidenced by upregulated TNF-α, IL-6, and caspase-3 at both gene and protein levels, alongside elevated nitric oxide synthase (NOS) and lactate dehydrogenase (LDH) activities (P < 0.05). While the Rictor/mTORC2 pathway regulates renal pathology, its role in B[a]P-induced injury remains unelucidated. Our study found that B[a]P exposure (7–14 days) significantly upregulated key components of and its downstream effectors (AKT1 and PKC-ζ) at both transcriptional levels (P < 0.05). Mechanistic studies in macrophage-specific Rictor knockout mice (Mac Rictor-/-) showed that, inhibiting Rictor/mTORC2 suppressed B[a]P-induced renal oxidative stress, inflammatory factor release, and apoptosis. This study first revealed that the Rictor/mTORC2 pathway serves as a potential molecular therapeutic target for B[a]P-induced kidney injury.