The effects of cannabidiol on certain adipokine, cardiac, intestinal and cerebral responses and lysosomal functionparameters in an experimental sepsis model induced by cecalligation and puncture in rats

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and/or superantigen. Adipokines are biomolecules secreted from adipose tissue that are effective in the regulation of inflammatory response, changes in energy metabolism and the development of organ damage during sepsis. The aim of this study was to investigate the effects of Cannabidiol (CBD) administration at different rates on adipokine (apelin, irisin, visfatin), cytokine (IL-6, TNF-α), cardiac (cTnI), intestinal (GLP-1) and cerebral (BDNF) responses and some lysosomal function (LAMP1) parameters in experimentally induced sepsis rats created by cecal ligation and puncture method. For this purpose, 88 adult male Wistar albino rats, aged between 8-10 weeks and weighing an average of 220-250 g, were used. Before the experiment, rats were randomly selected with equal average body weights and 7 groups were created as K (n=8), Sham (n=8), CLP (n=8), CLP + CBD 2.5 (n=16), CLP + CBD 5 (n=16), CLP + CBD 7.5 (n=16) and CLP + CBD 10 (n=16). The study groups are as follows: Control group (n=8): Rats that were not subjected to any treatment in order to determine the levels of the parameters constituting the subject of the study in normal healthy rats; Sham group (n=8): In order to determine the effects of surgical intervention on the investigated parameters, this group included subjects who did not undergo cecal ligation perforation (CLP), unlike the intra-abdominal sepsis model. Only rats in the laparotomy group were included. CLP group (n=8): Rats in the group in which sepsis (CLP) was induced by cecal ligation and puncture in order to create intra-abdominal sepsis. CLP + CBD 2.5 group (n=16): Rats in the group in which 2.5 mg/kg CBD was administered intraperitoneally and then sepsis was induced with CLP. At the 8th and 16th hours, 8 rats each were sacrificed and intracardiac blood was taken immediately afterwards. CLP + CBD 5 group (n=16): Rats in the group in which 5 mg/kg CBD was administered intraperitoneally and then sepsis was induced with CLP. At the 8th and 16th hours, 8 rats each were sacrificed and intracardiac blood was taken immediately afterwards. Rats were formed with a total of 88 rats as follows: CLP+CBD 7.5 group (n=16): Rats in which 7.5 mg/kg CBD was administered intraperitoneally and then sepsis was induced with CLP, 8 rats each were sacrificed at the 8th and 16th hours and intracardiac blood was taken immediately afterwards; CLP+CBD 10 group (n=16): Rats in which 10 mg/kg CBD was administered intraperitoneally and then sepsis was induced with CLP, 8 rats each were sacrificed at the 8th and 16th hours and intracardiac blood was taken immediately afterwards. Intracardiac blood samples were taken from the tail vein (vena caudalis) of rats in the CLP+ CBD 2.5, CLP+ CBD 5, CLP+ CBD 7.5 and CLP+ CBD 10 groups at the 8th hour of the study, and immediately after the rats in all groups in the study were sacrificed at the 16th hour of the study. Apelin, Irisin, Visfatin, IL-6 (Interleukin-6) and TNF-α (Tumor Necrosis Factor-alpha), Cardiac troponin I (cTnI), glucagon-like peptide 1 (GLP-1), Brain-Derived Neurotrophic Factor (BDNF) and lysosomal-associated membrane protein 1 (LAMP1) levels in the serum samples obtained from the blood samples were examined by ELISA method. All numerical data obtained as a result of the study were statistically analyzed by Duncan test in General Linear Model Univariate in the SPSS 26.0 statistical program. The means of the data were expressed with their standard errors and (±) Repeated measures test was used. All significant differences were evaluated by testing at p<0.05 level. In the CLP-2.5, CLP-5, CLP-7.5 and CLP-10 groups where sepsis was experimentally induced with the CLP method, an increase was observed in the mean serum irisin, BDNF, and LAMP1 levels at the 8th hour of the early response and the 16th hour of the late response due to the dose increase in CBD use, and the most significant increase was determined in the CLP-10 group. In the CLP-2.5, CLP-5, CLP-7.5 and CLP-10 groups in which sepsis was experimentally induced with the CLP method, the mean serum Visfatin, Apelin and TNF-α decreases due to the dose increase in CBD use. The most significant decrease was observed in the CLP-5 group, while the mean serum IL-6, cTnI and GLP-1 levels decreased the most significant decrease was determined in the CLP-10 group (p<0.05). As a result, it was concluded that 10 mg/kg CBD administration in rats did not cause any adverse effects, on the contrary, it may be beneficial in regulating sepsis-induced metabolic (apelin, irisin, visfatin), inflammation (IL-6, TNF-α), cardiac (cTnI), intestinal (GLP-1), lysosomal (LAMP1) and cerebral (BDNF) biomarker levels and cognitive functions.