ABSTRACT
This investigation explored the nilotinib action in the management of acute pancreatitis (AP) and AP-induced lung and liver injury. AP was induced in Sprague Dawley (SD) rats with L-arginine. Treatment with nilotinib with or without L-arginine was applied for 7 days. Marked deterioration in serum amylase, lipase, aspartate amino transferase (AST), alanine amino transferase (ALT), lactate dehydrogenase (LDH), nitric oxide (NO), total protein content, and transforming growth factor beta1 (TGF-ß1) along with pancreatic, hepatic, and pulmonary tissue lipid peroxidation (MDA) after induction of AP while significant reduction in tissues superoxide dismutase (SOD), glutathione (GSH) with marked edema, hemorrhage, and perivascular inflammation with acinar cell necrosis, along with elevated pancreatic percentage expression of TGF-ß1 and nuclear factor kappa B (NF-κB), were observed in the AP group. Nilotinib markedly ameliorated biochemical and histopathologic changes during AP, thus preserving the pancreas, liver, and lung histologically through mechanism involving antioxidant and anti-inflammatory actions.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Liver Diseases/prevention & control , Lung Injury/prevention & control , Pancreatitis/drug therapy , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Acute Disease , Amylases/blood , Animals , Arginine , Biomarkers/blood , Cytoprotection , Disease Models, Animal , Lipase/blood , Liver Diseases/blood , Liver Diseases/etiology , Liver Diseases/pathology , Lung Injury/blood , Lung Injury/etiology , Lung Injury/pathology , Male , NF-kappa B/metabolism , Nitrates/blood , Nitrites/blood , Pancreatitis/blood , Pancreatitis/chemically induced , Pancreatitis/pathology , Rats, Sprague-Dawley , Time Factors , Transforming Growth Factor beta1/bloodABSTRACT
Acute pancreatitis (AP) is an acute inflammatory disorder of the pancreas that can be complicated by involvement of other remote organs. Oxidative stress is known to have a crucial role in the development of pancreatic acinar damage and one of the main causes in multisystem organ failure in experimental AP. The aim of the study was to determine the effect of tiron on pancreas and remote organ damage in L-arginine (L-Arg) induced AP rat model. Thirty-two male rats were divided in random into four groups: control, tiron, L-Arg, and tiron with L-Arg. At the end of the experiment, blood samples were withdrawn for biochemical analysis. The pancreas, lung, kidney, and liver were collected for histopathological examination. Estimation of pancreatic water content was done. Analysis of pulmonary, hepatic, renal, and pancreatic lipid peroxide levels (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) were carried out. Finally, nuclear factor kappa B (NF-κB) and transforming growth factor ß1 (TGF-ß1) expression in pancreatic tissue was determined. Results indicated that treatment with tiron significantly decreased lipid peroxide levels and markedly increased both SOD activity and GSH level. Moreover, histopathological analysis further confirmed that administration of tiron relatively ameliorates pancreatic acinar cells and remote organ damage. Increased immunoreactivity of NF-κB and TGF-ß1 were reduced also by tiron treatment. These findings pointed out the protective role of the mitochondrial antioxidant, tiron against AP induced by L-Arg.
Subject(s)
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt/pharmacology , Antioxidants/pharmacology , Arginine , Multiple Organ Failure/prevention & control , Oxidative Stress/drug effects , Pancreas/drug effects , Pancreatitis/drug therapy , Acute Disease , Animals , Biomarkers/metabolism , Cytoprotection , Disease Models, Animal , Glutathione/metabolism , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/metabolism , Liver/pathology , Lung/drug effects , Lung/metabolism , Lung/pathology , Male , Malondialdehyde/metabolism , Multiple Organ Failure/chemically induced , Multiple Organ Failure/metabolism , Multiple Organ Failure/pathology , NF-kappa B/metabolism , Nitric Oxide/metabolism , Pancreas/metabolism , Pancreas/pathology , Pancreatitis/chemically induced , Pancreatitis/metabolism , Pancreatitis/pathology , Rats, Wistar , Severity of Illness Index , Superoxide Dismutase/metabolism , Transforming Growth Factor beta1/metabolismABSTRACT
INTRODUCTION: Sexual dysfunction and infertility are symptoms which have been rarely studied in patients treated with antischizophrenic drugs, aripiprazole and olanzapine, for long period. This work aimed to investigate the effects of aripiprazole and olanzapine on the structure of seminiferous tubules of rats at both light microscopic and ultrastructural levels. MATERIAL AND METHODS: Sixty adult male rats were divided into 3 groups (n = 20): control group (Group I) and two experimental ones (II and III). Rats in Group II received 2 mg/kg/day aripiprazole while rats in Group III received 0.5 mg/kg/day olanzapine for 14 weeks. Thereafter, testis were removed and processed for both light and electron microscopic study. Qualitative morphological analyses and histomorphometric measurements of seminiferous tubules were performed. RESULTS: Rats in Group II showed reduction of testicular weight, seminiferous tubules' diameter, epithelial height, spermatogenic count, spermatogenic index and spermatogenic score whereas Sertoli cells count was increased. Olanzapine-treated rats also showed epithelial desquamation, separation and apoptotic changes of germ cells. Sertoli cells showed vacuolization, dilatation of smooth endoplasmic reticulum and accumulation of lipid droplets. Abnormality in the shape and structure of late spermatids and presence of giant cells were also demonstrated. Aripiprazole induced less adverse histological changes in rat testis than olanzapine. CONCLUSIONS: Olanzapine followed by aripiprazole had adverse histological effects on the structure of the seminiferous tubules, which may affect spermatogenesis.
