Abstract
Topicality. Recently, more and more works on the hepatotoxicity of NSAIDs have appeared in the literature. Presumably, all NSAIDs have hepatotoxicity, but the degree of adverse effects on the liver in different drugs is variable. Aim. To study the effect of different generations of NSAIDs on the functional state of the liver of the experimental animals. Materials and methods. Diclofenac sodium, piroxicam, indomethacin, meloxicam and celecocosib were selected for the comparative study. Changes in the functional state of the liver of intact rats during subchronic administration of the drugs selected, as well as their impact on the course of the model hepatitis were determined. The state of the liver was determined by the following indicators: the mass coefficient of the liver, the activity of alanine aminotransferase, alkaline phosphatase, the content of total protein, urea, cholesterol in the blood serum, the level of TBA-active products, diene conjugates, reduced glutathione, catalase and glycogen in the liver homogenate. Results and discussion. It was found that diclofenac, piroxicam, indomethacin in the doses of ED50 by the antiexudative activity when used for 14 days adversely affected the liver of intact animals, as well as worsened the course of the model hepatitis, i.e. had a pronounced hepatotoxic effect. Meloxicam and celecoxib did not show a pronounced adverse effect in the carbon tetrachloride hepatitis, but contributed to the deterioration of the functional state of the liver of intact rats, i.e. had a moderate hepatotoxic effect. Conclusions. By the level of hepatotoxicity the drugs studied can be arranged as follows: diclofenac > indomethacin > piroxicam > meloxicam > celecoxib.
Highlights
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most popular groups of drugs
NSAID-associated side effects are the subject of large-scale scientific and practical discussions and the object of numerous experimental and clinical studies
MATERIALS AND METHODS Five widely used NSAIDs of different generations were selected for the comparative study, namely diclofenac sodium, piroxicam, indomethacin, meloxicam, and celecocoxib
Summary
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most popular groups of drugs. According to the WHO, about 20 % of the world’s population regularly uses drugs of this group [1]. It was previously believed that the main link in the pathogenesis of hepatotoxicity was inhibition of the prostaglandin synthesis. Recently this hypothesis has been revised [9, 10]. In the pathogenesis of the NSAID-associated liver damage, there is blockade of the enzyme systems of the Krebs cycle and the uncoupling of oxidative phosphorylation (similar to the Reye’s syndrome) in the mitochondria of hepatocytes, blockade of phosphodiesterase IV, impaired excretion of bile due to the formation of bulky complexes of NSAID metabolites with bile acids, enterohepatic treatment, as well as immunological disorders [11]. The problem of the hepatotoxic effect of some NSAIDs is so acute that in a number of countries these drugs are prohibited. In the USA, UK, Canada and Australia, the drug was not approved for registration [13]
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