In this work, we studied the variations in PON1 activity depending on the type of liver disease, in order to assess the value of this parameter in their diagnoses. We noted that PON1 activity was lower in patients compared to control group. In addition, the risk of having decreased PON1 activity was doubled in patients with liver damage. The significant decrease in PON1 activity in chronic liver disease could be explained by two mechanisms. Indeed, although hepatic PON1 concentrations may be normal, serum PON1 activity may be reduced. According to the study by Kedage et al. (2010), this decrease could be the consequence of an alteration in the synthesis and/or the secretion of secondary HDL-c due to a deficiency in Lecithin cholesterol acyltransferase (LCAT) . Indeed, changes in the structure or concentration of HDL, associated with a decrease in hepatic LCAT activity were frequent in chronic liver diseases. A decrease in serum PON1 activity was found in mice with LCAT deficiency resulting from disturbances of target genes . Zhang et al. (2008) reported that overexpression of PON1 provides strong protection against the experimental development of liver disease. However, low concentrations of PON1 were associated with an increased susceptibility to the development of hepatic parenchymal damage . The second mechanism was based on the fact that serum PON1 was mainly synthesized in the liver. Thus, there was expression of a defective gene, which contributes to a decrease in PON1 activity, in hepatic dysfunction . The modulation of PON1 activity by some factors including age, gender, tobacco, alcohol and diabetes should be taken into account. In the present work, we had found that only age and diabetes were confounding factors responsible, in part for the variations in PON1 activity.
Our study showed that the activity of transaminases, GGT, PALs, as well as bilirubin concentration were significantly higher in patients compared to control group. The increase in liver enzymes was a consequence of the increased membrane permeability of hepatocytes. It could give an indication of the lesional, rather than the functional origin of the liver disorder. Elevated serum transaminases activity informed on hepatocyte damage, while elevated PAL activity was a sensitive marker of cholestasis . Regarding GGT, an activity exceeding the usual values of this enzyme, constituted the most sensitive marker of hepatobiliary diseases, but its use in clinical routine was not recommended, since it could not by itself, provide information on the specific cause of hepatopathy. It was useful in the determination of the hepatic origin, in an isolated increase in PAL activity .
In the present study, the activity of PON1 varied from one liver disease to another. Hepatitis, any acute or chronic inflammation of the liver, could progress to a severe or fulminant form, cirrhosis or cancer. PON1 activity was significantly reduced in patients with chronic hepatitis compared to control group . Kilic et al. (2005) reported that PON1 activity was reduced by 64% in patients with chronic hepatitis compared to controls. They also noted a 20% reduction in HDL-c concentrations . Cirrhosis, the predominant liver disease in our population, was a chronic disease in which the liver becomes covered with fibrous tissue, causing the progressive degradation of liver tissue and filled with fatty tissue. The significant decrease in PON1 activity was more noted in patient with cirrhosis compared to those with hepatitis. This result was similar to that reported by Fedelesova et al., (2017) . However, in our present study, the decrease in PON1 activity showed a significant positive correlation with HDL-c in cirrhotics. Decreased activity in patients with cirrhosis was related to the degree of hepatic injury and correlated with blood bilirubin and albuminemia. On the other hand, HDL-c was significantly reduced in these same patients . Changes in PON1 activity were studied in other types of hepatic impairment that were not encountered in our practical investigation, in order to determine the level of PON1 activity in some disorders associated with hepatocellular damage, especially steatosis and non-alcoholic steatohepatitis [24–27]. Kotani et al., (2021) reported that PON1 activity was low in patients with non-alcoholic fatty liver disease, and this decrease was proven by biopsy. However, no significant difference was noted for the arylesterase activity of PON1 in these patients . PON1 was thought to act as a barrier against hepatic oxidative stress in certain types of liver damage [25–28]. Indeed, an increase in serum xanthine oxidase, generator of reactive oxygen species, a decrease in antioxidant capacities due to the reduce in the levels of superoxide dismutase, glutathione peroxidase, nitric oxide as well as a decrease in PON1 activity has been reported in some liver damage [25, 26]. Serum xanthine oxidase activity was negatively correlated with PON1 activity. Thus, PON1 could be inactivated by reactive oxygen species, possibly through the production of superoxide anions.
In the present study, significantly lower PON1 activity was noted in patients with IHC syndrome compared to those without this syndrome. Hypoprotidemia and hypoalbuminemia were interested biological markers, but nonspecific in IHC disease. They result from a reduction in synthesis, reflecting the functional insufficiency of the hepatic parenchyma. Thus, in hypoalbuminemia the activity of PON1 could be used to guide or confirm the diagnosis of IHC.
In this study, we noted that the variation on PON1 activity, according HDLc concentrations. In fact, a significantly low activity of PON1 was found in patients with a low level of HDLc, compared to those that had a level in the range of usual values. In addition, a positive correlation was found between PON1 activity and serum HDLc concentrations. We also noted that the activity of PON1 was even lower as the number of lipid parameters was high.
Indeed, PON1 was localized on the surface of HDL. These lipoproteins play a central role in atheroprotection which, together with their major apolipoproteins Apo-A1, play an important role in the reverse transport of cholesterol. They bring the efflux of this latter from the peripheral tissues to the liver. In addition, HDL levels exert protective effects by reducing systemic and local inflammation. This process was mainly represented by the protection of LDL from oxidation, which prevents the recruitment and the migration of inflammatory cells to the arterial wall .
The anti-atherogenic and antioxidant effects of HDL should be attributed to the levels of associated proteins such as apoA-j, LCAT, and PON1. Indeed, the protection against the oxidation of LDL was provided by HDL and purified PON1. These two latter molecules prevent the generation of lipoperoxides during the oxidation of LDL, suggesting that this enzyme may be involved in the protective function of HDL . These results could explain the significant correlation between PON1 activities and HDL-c concentrations. In addition, PON1 protects the lipids present in lipoproteins, in macrophages and in erythrocytes from oxidation. In fact, the protection against the process of lipid peroxidation was ensured by the degradation of cholesterol esters and oxidized lipids by hydrolysis of oxidized lipoproteins [29, 31].