Korean J Physiol Pharmacol.  2021 Jan;25(1):69-77. 10.4196/kjpp.2021.25.1.69.

The effect of adenosine triphosphate on propofol-induced myopathy in rats: a biochemical and histopathological evaluation

• Erdem KTO
• Bedir Z
• Ates I
• Kuyrukluyildiz U
• Coban TA
• Yazici GN
• Arslan YK
• Suleyman Z
• Suleyman H

• KMID: 2509656
• DOI: http://doi.org/10.4196/kjpp.2021.25.1.69

Abstract

Propofol infusion syndrome characterized by rhabdomyolysis, metabolic acidosis, kidney, and heart failure has been reported in long-term propofol use for sedation. It has been reported that intracellular adenosine triphosphate (ATP) is reduced in rhabdomyolysis. The study aims to investigate the protective effect of ATP against possible skeletal muscle damage of propofol in albino Wistar male rats biochemically and histopathologically. PA-50 (n = 6) and PA-100 (n = 6) groups of animals was injected intraperitoneally to 4 mg/kg ATP. An equal volume (0.5 ml) of distilled water was administered intraperitoneally to the P-50, P-100, and HG groups. One hour after the administration of ATP and distilled water, 50 mg/kg propofol was injected intraperitoneally to the P-50 and PA-50 groups. This procedure was repeated once a day for 30 days. The dose of 100 mg/kg propofol was injected intraperitoneally to the P-100 and PA-100 groups. This procedure was performed three times with an interval of 1 days. Our experimental results showed that propofol increased serum CK, CK-MB, creatinine, BUN, TP I, ALT, AST levels, and muscle tissue MDA levels at 100 mg/kg compared to 50 mg/kg and decreased tGSH levels. At a dose of 100 mg/ kg, propofol caused more severe histopathological damage compared to 50 mg/ kg. It was found that ATP prevented propofol-induced muscle damage and organ dysfunction at a dose of 50 mg/kg at a higher level compared to 100 mg/kg. ATP may be useful in the treatment of propofol-induced rhabdomyolysis and multiple organ damage.

Keyword

Adenosine triphosphate; Muscle; Myopathy; Propofol; Rat; Rhabdomyolysis

Figure

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  Fig. 1 CK, CK-MB, BUN, and TP I levels in the blood of the study groups. All groups were compared with HG (n = 6). CK, creatine kinase; CK-MB, creatine kinase MB; BUN, blood urea nitrogen; TP I, troponin-I; ATP, adenosine triphosphate; HG, healthy controls.

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  Fig. 2 ALT, AST, and LDH activity in the blood of the study groups. All groups were compared with HG (n = 6). ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; ATP, adenosine triphosphate; HG, healthy controls.

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  Fig. 3 MDA and tGSH levels in skeletal muscle tissue of the study groups. All groups were compared with HG (n = 6). MDA, malondialdehyde; tGSH, total glutathione; ATP, adenosine triphosphate; HG, healthy controls.

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  Fig. 4 Hematoxylin-eosin (H&E) staining in skeletal muscle tissue in the healthy group. ⮚, muscle cell nucleus; ►, muscle fibers; ★, blood vessel (H&E, ×200).

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  Fig. 5 Hematoxylin–eosin staining in skeletal muscle tissue in the low-dose (50 mg/kg) propofol group. (A) Hematoxylin-eosin (H&E) staining in skeletal muscle tissue in the low-dose (50 mg/kg) propofol group. ⮚, muscle cell nucleus; ►, degenerated pale muscle fibers with swollen, irregular appearance; ★, congested blood vessel; 🟀, polymorphonuclear cell infiltration (H&E, ×200). (B) H&E staining in skeletal muscle tissue in the low-dose (50 mg/kg) propofol + ATP group. ⮚, muscle cell nucleus; ►, decreased degeneration in muscle fibers with regular color and alignment; ★, normal blood vessel (H&E, ×200). (C) H&E staining in skeletal muscle tissue in the high-dose (100 mg/kg) propofol group. ⮚, disorganized and degenerated muscle cell nucleus; ►, irregular, ruptured and degenerated muscle fibers; ★, congested and dilated blood vessel; 🟀, numerously polymorphonuclear cell infiltration (H&E, ×200). (D) H&E staining in skeletal muscle tissue in the high-dose (100 mg/kg) propofol + ATP group. ⮚, normal muscle cell nucleus; ►, mostly normal organized and decreased degeneration in muscle fibers; 🟀, the spot of polymorphonuclear cell infiltration; ★, mildly congested blood vessel (H&E, ×200).

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