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

Area of Science:

• Toxicology
• Environmental Health
• Molecular Biology

Background:

• Benzo[a]pyrene (B[a]P) is a persistent organic pollutant known for its nephrotoxic effects.
• The toxicological profile of short-term, high-dose B[a]P exposure on the kidney is not fully understood.

Purpose of the Study:

• To investigate the time-dependent renal injury induced by a single high dose of B[a]P in mice.
• To elucidate the role of the Rictor/mTORC2 pathway in B[a]P-induced nephrotoxicity.

Main Methods:

• A C57BL/6J mouse model was used with a single oral dose of 50 mg/kg B[a]P.
• Biochemical markers (Scr, BUN, MDA, SOD, CAT, T-AOC, NOS, LDH) and molecular indicators (TNF-α, IL-6, caspase-3, Rictor, AKT1, PKC-ζ) were assessed.
• Macrophage-specific Rictor knockout mice (Mac Rictor-/-) were utilized for mechanistic studies.

Main Results:

• B[a]P exposure led to significant increases in serum creatinine and BUN, elevated oxidative stress markers (MDA), and reduced antioxidant capacity (SOD, CAT, T-AOC) within 3 days.
• Renal inflammation and apoptosis were observed from days 7-14, indicated by upregulated TNF-α, IL-6, and caspase-3.
• B[a]P upregulated the Rictor/mTORC2 pathway components and its effectors (AKT1, PKC-ζ).
• Inhibition of Rictor/mTORC2 in Mac Rictor-/- mice ameliorated B[a]P-induced renal oxidative stress, inflammation, and apoptosis.

Conclusions:

• The Rictor/mTORC2 pathway plays a critical role in mediating B[a]P-induced kidney injury.
• Targeting the Rictor/mTORC2 pathway presents a potential therapeutic strategy for B[a]P nephrotoxicity.