Volume 39 Issue 11
Nov.  2023
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Yu JA,Wang JZ,Wang JQ,et al.Effects of modified lytic cocktail on organ function of severely scalded rats[J].Chin J Burns Wounds,2023,39(11):1064-1071.DOI: 10.3760/cma.j.cn501225-20230329-00105.
Citation: Yu JA,Wang JZ,Wang JQ,et al.Effects of modified lytic cocktail on organ function of severely scalded rats[J].Chin J Burns Wounds,2023,39(11):1064-1071.DOI: 10.3760/cma.j.cn501225-20230329-00105.

Effects of modified lytic cocktail on organ function of severely scalded rats

doi: 10.3760/cma.j.cn501225-20230329-00105
Funds:

General Program of National Natural Science Foundation of China 82072173, 82172199

Shanghai Directed Projects of Biopharmaceutical Field 22DX1900600

Shanghai Municipal Key Clinical Specialty of China shslczdzk02302

Shanghai Specialized Research Fund for Integrated Chinese and Western Medicine in General Hospitals ZHYY-ZXYJHZX-201911

More Information
  • Corresponding author: Liu Yan, Email: rjliuyan@126.com
  • Received Date: 2023-03-29
  •   Objective   To compare the effects of the modified lytic cocktail and the classic lytic cocktail on organ function of severely scalded rats.   Methods   The experimental study method was applied. Twenty-four about 10-week-old male Sprague-Dawley rats were assigned into sham injury group, scald alone group, classic lytic cocktail group, and modified lytic cocktail group according to the random number table, with 6 rats in each group. In scald alone group, classic lytic cocktail group, and modified lytic cocktail group, rats were subjected to a 30% total body surface area (TBSA) full-thickness scald on the back. Rats in sham injury group underwent a simulated injury process to mimic a sham injury. Immediately after injury, rats in classic lytic cocktail group were intraperitoneally injected with a classic lytic cocktail (12 mL/kg) consisting of pethidine, chlorpromazine, and promethazine, supplemented with gavage using normal saline; and rats in modified lytic cocktail group were intraperitoneally injected with a mixed drug (2 mL/kg) consisting of midazolam and fentanyl, supplemented with gavage using cetirizine. Subsequently, rats in four groups were all intraperitoneally injected with lactated Ringer's solution for fluid resuscitation, with a total fluid and administration volume of 2 mL·kg -1·TBSA -1. On the following day, rats in the two lytic cocktail groups were administered medication once again as above. On post injury day (PID) 3, the abdominal aortic blood, liver, small intestine, and lung tissue were collected from rats in each group. The plasma levels of interleukin-1β (IL-1β), IL-10, and IL-6 were measured using an enzyme-linked immunosorbent assay. The plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (γ-GT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), LDH isoenzyme 1 (LDH-1), creatine kinase (CK), CK isoenzyme (CK-MB), urea, creatinine, and uric acid were detected using an automated biochemical analyzer. The histological changes of liver, small intestine, and lung tissue were observed after performing hematoxylin and eosin staining. Data were statistically analyzed with one-way analysis of variance and Tukey's test.   Results   On PID 3, the plasma level of IL-10 of rats in classic lytic cocktail group was (44±16) pg/mL, which was significantly higher than (20±9) pg/mL in modified lytic cocktail group and (21±6) pg/mL in scald alone group (with Pvalues all <0.05); there was no statistically significant difference in the plasma levels of IL-1β or IL-6 of rats among the four groups ( P>0.05). On PID 3, the plasma levels of ALT and AST of rats in scald alone group were (77±14) and (213±65) U/L, respectively, which were significantly higher than (59±5) and (108±10) U/L in sham injury group ( P<0.05); the plasma levels of ALT and AST in modified lytic cocktail group were (61±3) and (116±11) U/L, respectively, which were significantly lower than (81±13) and (207±54) U/L in classic lytic cocktail group ( P<0.05); the plasma level of AST of rats in modified lytic cocktail group was significantly lower than that in scald alone group ( P<0.05). On PID 3, there was no statistically significant difference in the plasma levels of γ-GT, ALP, LDH, LDH-1, CK, CK-MB, creatinine, or uric acid of rats among the four groups ( P>0.05); although there was a statistically significant overall difference in the plasma level of urea of rats among the four groups ( P<0.05), the comparisons between scald alone group and each of sham injury group, classic lytic cocktail group, and modified lytic cocktail group, and the comparison between classic lytic cocktail group and modified lytic cocktail group showed no statistically significant differences ( P>0.05). On PID 3, compared with those in sham injury group, rats in scald alone group exhibited diffuse microvesicular and vacuolar degeneration of hepatocytes in liver tissue, noticeable loose edema in the villous stroma in small intestine tissue, and significantly widened alveolar septa in large area of lung tissue. Compared with those in scald alone group, rats in the two lytic cocktail groups showed alleviated hepatocellular steatosis and vacuolar degeneration, relieved thickening of alveolar walls and edema in the villous stroma of the intestine. The histopathological manifestations of organs in rats of modified lytic cocktail group were closer to those in sham injury group.   Conclusions   The classic lytic cocktail may have a stronger anti-inflammatory effect, while the modified lytic cocktail exhibits better protection of liver function, but both of the two lytic cocktails can alleviate the histopathological injury of the liver, lungs, and small intestine in severely scalded rats. For the liver, lungs, and small intestine, the modified lytic cocktail provides organ protection comparable to that of the classic lytic cocktail.

     

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