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Pyridoxamine protects proteins from damage by hypohalous acids in vitro and in vivo

Hartman Madu1, Josh Avance1, Sergei Chetyrkin1

  • 1Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Free Radical Biology & Medicine
|July 11, 2015
PubMed

Insights

Pyridoxamine (PM) protects against diabetic kidney damage by neutralizing harmful hypohalous acids. This action, a novel mechanism, may explain PM

Area of Science:

  • Biochemistry
  • Nephrology
  • Endocrinology

Background:

  • Diabetes mellitus involves oxidative and glycoxidative stress, contributing to complications.
  • Pyridoxamine (PM) shows therapeutic promise for diabetes, but its in vivo mechanism is unclear.
  • Renal collagen IV is vulnerable to damage from hypohalous acids in diabetes.

Purpose of the Study:

  • To elucidate the in vivo mechanism of pyridoxamine (PM) in diabetic nephropathy.
  • To investigate PM's protective effects against hypohalous acid-induced damage.

Main Methods:

  • Assessed PM's reaction with hypochlorous and hypobromous acids in vitro.
  • Evaluated PM's ability to protect protein functionality from oxidative damage.
  • Examined PM's effects on renal collagen IV structure and function in a diabetic animal model.

Main Results:

  • Pyridoxamine (PM) directly reacts with and detoxifies hypohalous acids.
  • PM protects protein functionality from damage caused by hypohalous acids.
  • PM treatment ameliorates hypohalous acid-induced damage to renal collagen IV in diabetic rats.

Conclusions:

  • Pyridoxamine (PM) acts by sequestering hypohalous acids, a novel mechanism in diabetes.
  • This sequestration may underlie PM's therapeutic benefits in diabetic nephropathy.
  • PM offers a potential strategy to mitigate diabetic complications via direct detoxification.
Keywords:
DiabetesFree radicalsHypobromous acidHypochlorous acidNephropathyPosttranslational modificationsProtein halogenationPyridoxamine

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