Pharmacological correction of metabolic disorders in experimental acute pancreatitis on the background of chronic alcohol intoxication

Abstract

Introduction. Acute pancreatitis and pre-existing diseases (chronic alcohol intoxication) are challenging issues of modern surgery in terms of frequency of deaths and the number of complications.

Objective. To identify the best combination of immunomodulators, antioxidants and hepatoprotectors to correct immunometabolic disorders in acute destructive pancreatitis on the background of chronic alcohol intoxication (CAI).

Materials and methods. Studies were conducted on 377 healthy adult Wistar rats weighing 150-200 g. Alcohol intoxication was modeled by forced intragastric administration of a 20% ethanol solution at a dose of 3 ml/kg or 2.92 g/kg at 24 hours for 5 days, 30 days (CAI-30) or 60 days (CAI-60). Acute destructive pancreatitis (ADP) was modeled after R.N. Wang et al. (1995), modified by S.A. Alekhin et al. (2006). The efficacy of combining Hepon (5 mg/kg, orally, at 24 hours, No. 14), Hypoxen (750 mg/kg, orally, at 24 hours, No. 14), Phosphogliv (800 mg/kg, orally, at 24 hours, No. 14), Glutoxim (20 mg/kg, intramuscularly, at 24 hours, No. 5), Mexidol (50 mg/kg, intraperitoneally, at 24 hours, No. 14) and Heptral (760 mg/kg, intraperitoneally, at 24 hours , No. 5) was examined in animals with ADP on the background of CAI-30 and CAI-60.

Results and discussion. Different degrees of ethanol intoxication depending on time leads to the development of an impaired capacity of hepatocytes, as well as immune and metabolic disorders. The administration of Phosphogliv, Hypoxen and Hepon in case of CAI-30+ADP normalizes 12.1% and corrects 60.6% of the changed values. The combination of Heptral, Glutoxim and Mexidol normalizes 57.8% and corrects 42.4% of the values. In case of CAI-60+ADP, Phosphogliv, Hypoxen and Hepon normalizes 11.8% and corrects 38.2% of the values. The combination of Heptral, Glutoxim and Mexidol normalizes 17.6% and corrects 67.6% of the values, respectively.

Conclusion. In case of ADP along with CAI-30 and CAI-60, the combination of Heptral, Glutoxim and Mexidol is more preferable than that of Phosphogliv, Hypoxen and Hepon.