Oxidative and nitrosative damage, as well as inflammatory processes, could contribute to the pathophysiology of lysosomal acid lipase deficiency (LAL-D), according to a new study conducted by researchers from Brazil.
“We can suggest that the study of the potential benefit of the use of antioxidant and anti-inflammatory substances as an adjuvant tool in the treatment of patients with LAL-D should be increasingly considered and should be associated with the already recommended therapy based on the use of cholestyramine and statins (to lower cholesterol and [apolipoprotein B] synthesis), and enzyme replacement therapy with recombinant [lysosomal acid lipase (LAL)],” the study team wrote in Biochemistry and Cell Biology.
The study identified several biochemical alterations in patients with LAL-D vs age-matched controls. Patients with LAL-D showed increased chitotriosidase enzyme activity, increased concentration of cholestane-3β,5α,6β-triol, and enhanced formation of reactive species.
Moreover, the researchers found a positive correlation between chitotriosidase activity and plasma levels of cholestane-3β,5α,6β-triol oxysterol in patients with LAL-D.
Read more about LAL-D etiology
Patients with LAL-D also had lower plasma sulfhydryl content and higher levels of Di-tyr in the urine, which suggests oxidative damage to proteins.
Furthermore, patients with LAL-D showed increased levels of thiobarbituric acid reactive substances, the end product of membrane fatty acid peroxidation, and urinary isoprostanes, as well as higher levels of total cholesterol and low-density lipoprotein cholesterol.
The analysis of reactive nitrogen species suggested increased nitric oxide, nitrate, and nitrite production; however, the results did not achieve statistical significance.
The researchers analyzed plasma and urine samples from 6 patients with LAL-D (mean age, 18.2±19.64 years) who were receiving statin therapy. The diagnosis of LAL-D was confirmed by the absence of LAL activity in leukocytes.
Guerreiro G, Deon M, Vargas CR. Evaluation of biochemical profile and oxidative damage to lipids and proteins in patients with lysosomal acid lipase deficiency. Biochem Cell Biol. Published online April 12, 2023. doi:10.1139/bcb-2022-0330