Sepsis is a complex, destructive condition accompanied by high mortality and limited treatment options. Despite improved surgical techniques and intensive care treatments, sepsis-related mortality rates remain high and continue to be a significant cause of hospital deaths [18–20]. For all these reasons, new and effective treatment methods for sepsis are of great importance.
Multiple organ failure is the usual cause of death from sepsis. Lysosomal enzymes and free oxygen radicals, especially released by neutrophils, participate in the pathogenesis of organ failure [21]. Various antioxidants have been used to prevent accumulation of free oxygen radicals, which participate in mortality due to sepsis.
Extracts of Petroselinum crispum in vitro and in vivo have been reported to possess antioxidant properties [22, 23]; we have found no report of its protective effects against sepsis.
We used CLP induced sepsis as our model. Sepsis was verified by hemogram (neutrophils, lymphocytes), biochemical (AST, ALT, LDH, BUN, TAS, TOS and OSI levels) and histopathological changes, which are used to confirm sepsis In the comparison between Sham and CLP groups, the increase in the OSI level means that CLP increases oxidative stress, while its decrease between CLP and PcE + CLP groups means that PcE reduces sepsis induced oxidative stress.
We found a significant decrease in TAS in the intestinal tissue extracts It is described in Methods Even though the decrease in TAS level in CLP group according to Sham group, the increase in PcE + CLP group according to CLP group was not statistically significant, it was significant in that it showed that CLP induced sepsis while PcE reduced it. Previous studies have shown that antioxidant markers are diminished in sepsis via CLP. In a study by Ritter et al., It was demonstrated that antioxidant enzymes such as catalase and superoxide dismutase activity were reduced in essential organs involved in the septic response [24]. [25] reported the increase of glutathione level of parsley extract. With this result, it was concluded that parsley extract had a protective effect due to its antioxidant properties. All of these previous studies show that sepsis increases oxidative stress and the antioxidant system decreases. In the present study, this situation was shown with the change in TOS, OSI and TAS levels. We did not show them one by one, but as oxidative stress markers (TOS, OSI) and antioxidant markers (TAS).
The oxygen-free radicals containing malondialdehyde (MDA), hydrogen peroxide and hydroxyl radicals cause peroxidative stress. Reduced antioxidative defenses, such as superoxide dismutase, catalase, and glutathione (GSH), also contribute to oxidative stress. Then, organ failure occurs [26]. In this study, it was observed that parsley extract had a protective effect against CLP, with biochemical and histopathological analyzes showing that it reduces multi-organ damage. This protective effect is primarily due to the inhibition of oxidative stress, which is one of the most important mechanisms of organ injury in sepsis. In our current study, it has been proven that the administration of parsley extract before CLP-induced sepsis increases neutrophil, PLT counts and TAS levels which decrease with sepsis and decreases biochemical changes (BUN, AST, ALT, LDH, TOS, OSI) which increase with sepsis, to have a protective effect on sepsis .
Histopathological changes that were determined that epithelial damage and infiltration severity increased, crypt-villus length, Paneth cell hypertrophy, and its cytoplasm granules decreased in the CLP group supported sepsis syndrome. These changes have been confirmed by previous studies [27]. The intestinal histological changes, including significantly reduced of the severity of infiltration, were reversed by the use of PcE. This situation showed us the protective effect of PcE on intestinal mucosa in sepsis. In the current study, we evaluated apoptosis by caspase-3 activity. Caspase-3 activity decreased significantly in the CLP group compared to the Sham group and a significant increase in PcE + CLP groups compared to the CLP group can be interpreted as parsley extract has apoptosis-inducing activities and protective effects. The histopathological and biochemical results obtained in this study were similar to previous studies [28, 29].
As shown in previous studies, in this study, the decrease in the TOS and OSI levels, as well as their histopathological changes such as especially a reduction of intestinal infiltration, were demonstrated the antioxidant properties of PcE [30, 31]. In further research, we think that the content of parsley extract will be elucidated in more detail by chromatographic methods, and the active substances or plant-prepared bioactive fractions isolated from the plant will offer alternative treatment options.
As result, especially in hospitalized patients or other patients at risk for sepsis; we believe that our research may be the first step for a drug that can be developed to reduce the risk of sepsis and facilitate the treatment.