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Interference with TGFβ1-Mediated Inflammation and Fibrosis Underlies Reno-Protective Effects of the CB1 Receptor

Basma G Eid1, Thikryat Neamatallah1, Abeer Hanafy1,2

  • 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Molecules (Basel, Switzerland)
|February 10, 2021
PubMed

Insights

Neutral CB1 receptor antagonists AM6545 and AM4113 show reno-protective effects in metabolic syndrome (MetS) rats. These compounds reduced proteinuria, inflammation, and fibrosis, suggesting a therapeutic role in kidney disease.

Area of Science:

  • Nephrology
  • Pharmacology
  • Metabolic Syndrome Research

Background:

  • Metabolic syndrome (MetS) is linked to kidney damage.
  • Cannabinoid receptor 1 (CB1) antagonists are being explored for therapeutic potential in nephropathy.

Purpose of the Study:

  • To investigate the effects of two neutral CB1 receptor antagonists, AM6545 and AM4113, on kidney damage in a rat model of MetS.

Main Methods:

  • MetS was induced in rats via high-fructose, high-salt diet.
  • Rats received either AM6545 (peripheral antagonist) or AM4113 (central antagonist) for 4 weeks.
  • Kidney function, histopathology, and transforming growth factor beta 1 (TGFβ1) levels were assessed.

Main Results:

  • Both AM6545 and AM4113 reduced proteinuria and albuminuria without affecting blood pressure or creatinine clearance.
  • The antagonists alleviated kidney swelling, inflammation, and histopathological damage.
  • Both compounds prevented increased uric acid excretion, collagen deposition, and elevated TGFβ1 expression.

Conclusions:

  • AM6545 and AM4113 demonstrate reno-protective effects in MetS-induced nephropathy.
  • These effects are mediated by inhibiting TGFβ1-driven renal inflammation and fibrosis.
  • The findings suggest a therapeutic benefit of CB1 receptor antagonists in managing kidney complications of metabolic syndrome.
Keywords:
AM4113AM6545cannabinoidskidneymetabolic syndromerats

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