Hepatoprotective Effect Of Trypsin/Chymotrypsin Against Olanzapine-Induced Non-Alcoholic Steatohepatitis In Rats
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY(2021)
Abstract
Metabolic side effects of atypical antipsychotics are an important cause of deterioration of cognitive function and failure of drug adherence. The antifatty effect trypsin/chymotrypsin (T/C) and their mechanisms of action remain unclear. To investigate possible therapeutic effect of T/C in rat model of chronic olanzapine (OLZ) - induced hepatic steatosis. Twenty rats were divided into two groups: control (C), given distilled water, and O, given 1 mgficg of OLZ orally daily for 7 weeks. Then, both groups were given T/C 3 enzyme activity unit (EAU)/kg orally as an add-on treatment daily for the next 5 weeks and were named T/C or T/C+O groups. Rat performance in radial arm water maze was tested twice before and after T/C treatment. We measured liver enzymes, alpha-1 antitrypsin, albumin, total protein, direct and total bilirubin, inflammatory cytokines, and lipoprotein serum levels. Liver samples were collected for histopathology and 1067 expression. The T/C add-on caused significant reduction in OLZ-induced elevation of alanine transaminase (ALT; P < 0.01), aspartate transaminase (AST; P < 0.001), alkaline phosphatase (ALP; P < 0.05), total cholesterol (Tc; P < 0.01), low-density lipoproteins (LDL-c; P < 0.05), steatosis score (P < 0.001), hepatocyte necrosis (P < 0.01), and significantly increased Ki67 expression (P < 0.01). The T/C add-on to OLZ provided protection against hepatic steatosis, elevated enzymes, and disturbed lipid profile and increased 1067 without disturbing memory function.
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Key words
trypsin/chymotrypsin, olanzapine, steatohepatitis, radial arm water maze, lipoproteins, liver enzymes
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