Peculiarities of protein metabolism in nimesulide-induced liver injury and its restoration under the influence of cell-free cryopreserved biological agents
DOI:
https://doi.org/10.32782/2415-8127.2026.73.9Keywords:
nimesulide, liver, total protein, albumins, globulins, cryoextract, cryopreservation, mesenchymal stem cellsAbstract
Nimesulide is a selective cyclooxygenase-2 inhibitor widely used for the treatment of acute pain and inflammatory conditions; however, its use is associated with a risk of toxic liver injury. One of the key manifestations of such damage is suppression of the synthetic function of hepatocytes accompanied by decreased plasma protein levels, particularly albumins. Hypoalbuminemia reflects impaired hepatic protein synthesis and has important pathophysiological and prognostic significance.
Objective: To characterize protein metabolism disturbances in rats with nimesulide-induced liver injury and to evaluate the restorative efficacy of cell-free cryopreserved biological agents compared with the reference hepatoprotective drug, Silibor.
The study was performed on 42 rats weighing 200–220 g divided into six groups. Liver injury was induced by intragastric administration of nimesulide at a dose of 80 mg/kg for five days. Animals received Silibor 50 mg/kg, cryoextract of placenta 2.5 ml/kg, cryoextract of spleen 5.0 ml/kg, and conditioned medium of mesenchymal stem cells 0.6 ml/kg. On day 10, total protein, albumins, and globulins were determined in blood serum.
Nimesulide administration caused a pronounced impairment of protein homeostasis: total protein decreased to 36.0 g/L and albumins to 12.0 g/L, resulting in a reduced albumin-to-globulin ratio of 0.6. This profile indicates hepatic synthetic insufficiency. Silibor partially corrected these disturbances: total protein increased to 52.0 g/L and albumins to 24.0 g/L. The most pronounced recovery was observed after administration of cryoextract of placenta and cryoextract of spleen: albumin levels reached 31.0 and 30.0 g/L, respectively; total protein approached intact values, and the albumin-to-globulin ratio improved markedly (with normalization observed primarily in the placenta cryoextract group). Conditioned medium of mesenchymal stem cells also increased total protein and albumins; however, it was accompanied by a relatively higher globulin level, which may reflect an immunomodulatory component of its action.
Five-day administration of nimesulide leads to a marked suppression of the hepatic protein-synthesizing function with a decrease in the albumin-to-globulin ratio. Silibor provides partial correction of these disturbances. The most effective restoration of the protein profile and indicators of hepatic synthetic function is achieved with cryoextract of placenta and cryoextract of spleen.
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