Modulation of the proteolytic cascade systems by high dose corticosteroids

Area of Science:

• Biochemistry
• Pharmacology
• Physiology

Background:

• Proteolytic cascade systems play a crucial role in physiological and pathological processes.
• High-dose corticosteroids (HDC) are used clinically, but their precise effects on proteolytic cascades require further elucidation.
• Acute pancreatitis involves complex inflammatory and proteolytic pathways.

Purpose of the Study:

• To investigate the in vitro and in vivo effects of HDC on proteolytic cascade systems.
• To evaluate the efficacy of HDC as a pretreatment for experimental acute pancreatitis in pigs.

Main Methods:

• In vitro studies utilized chromogenic peptide substrate assays to assess enzyme activities in plasma.
• In vivo studies involved inducing acute pancreatitis in pigs and administering methylprednisolone sodium succinate as pretreatment.
• Measurements included plasma prekallikrein, prothrombin, plasminogen, kallikrein, trypsin, cardiac output, and mean arterial pressure.

Main Results:

• In vitro, HDC significantly inhibited plasma prekallikrein, prothrombin, and plasminogen activation, and reduced inhibitory activities.
• In pigs with pancreatitis, untreated animals showed reduced plasma prekallikrein, increased kallikrein activity, and high trypsin activity, with a 63% mortality rate.
• HDC pretreatment in pigs prevented mortality, improved hemodynamic parameters (cardiac output, mean arterial pressure), and modulated plasma kallikrein and prekallikrein levels in peritoneal exudate.

Conclusions:

• HDC exerts significant inhibitory effects on key components of the proteolytic cascade.
• HDC pretreatment offers protective benefits in experimental acute pancreatitis, improving survival and hemodynamic stability.
• HDC may modulate the inflammatory response in pancreatitis by influencing proteolytic enzyme activities.