Gastric injury induced by I/R is a possible clinical problem to appear in many conditions such as peptic ulcer bleeding, hemorrhagic shock and surgery (Kuyrukluyildiz et al., 2021).
In the literature, I/R injury has been defined as a pathological event that begins with ischemia, continues with oxidative stress and expands with inflammation (Kocaturk et al., 2020).
In this study, the protective effect of desloratadine against possible gastric injury induced by I/R was analyzed biochemically and histopathologically.
As known, I/R causes oxidative stress with the increase in ROS production (Ding et al., 2021).
ROSs oxidizes cell membrane lipids, causing an increase in toxic oxidant products such as MDA (Xuying et al., 2022).
As seen in Table 1, MDA levels in gastric tissues of the animals in GIR group underwent gastric I/R were found higher than in sham group (p
<0.001). Similarly, Omayone et al., found
that MDA levels increased in gastric tissue applied I/R (Omayone et al., 2020).
Table 1: Analysis results of biochemical parameters in stomach tissues of animal groups.
This study analyzed non-enzymatic and enzymatic antioxidant levels such as tGSH, SOD and CAT besides oxidant parameter measurement. Cellular protection against the oxidation of ROS was mainly provided by GSH, SOD and CAT (Poljsak et al., 2013; Ravikumar et al., 2022).
In the literature, there was information about GSH having various physiological functions including ROS scavenging and electrophile elimination (Liu et al., 2022). Kuyrukluyildiz et al., (2021)
determined that I/R procedure decreased tGSH levels in the stomach tissue. In this study, in group comparisons performed in terms of tGSH levels, the values in GIR group were determined lower than the healthy animals (p
<0.001, Table 1). SOD as an enzymatic antioxidant analyzed in this study was considered to be the first defense line that eliminated the superoxide radical (O2
") formed in the body (Cui et al., 2013).
It was stated by Cui et al., that
the decrease in SOD levels due to gastric I/R was induced by the depletion of antioxidant capacity due to oxidative stress (Cui et al., 2013).
Supporting this information, our biochemical results determined that SOD levels were lower in the I/R group than in the GSG group (p
<0.001, Table 1). Another parameter measured in gastric tissue was CAT. It is known that CAT has been known to be an enzyme that decomposed hydrogen peroxide into molecular oxygen and water (He et al., 2017).
In our study, the CAT level was found to be lower in the I/R group with high MDA and low tGSH and SOD levels compared to healthy animals (p
<0.001, Table 1). Similarly, Odukanmi et al., found
that CAT levels were decreased due to I/R-induced damage in the stomach (Odukanmi et al., 2018).
Literature information and our experimental results suggested that exposure of the stomach to I/R caused oxidative stress, the oxidants increased and antioxidant levels decreased after depletion.
It was understood from the literature that inflammatory events also played roles in I/R injury (Kocaturk et al., 2020).
Therefore, IL-6 levels were determined to analyze the inflammatory activity in this study. Our biochemical results revealed that IL-6 levels in the GIR group were increased compared to the healthy group (p<0.001, Table 1). The increase in IL-6 levels occurs in cases such as oxidative tissue damage due to increased ROS. Because induced oxidative stress activates the transcription factor of NF-κB, which regulated IL-6 expression and this results in more IL-6 production (Kumari et al., 2016).
On the other hand, IL-6 expression also causes an increase in ROS production (Han et al., 2021). Magierowska et al., also
revealed that gastric I/R in rats increased IL-6 (Magierowska et al., 2019).
I/R injury on the gastric tissue was also analyzed histopathologically. As seen in Fig 1A and Table 2, tunica mucosa surface epithelium and glands, gastric stratification and wall structure were considered normal in gastric tissues of animals in the GSG group. In the sections belonging to the GIR group, the surface epithelium was monitored to be partially ruptured and shed; and necrotized cell groups were observed under the spilled surface epithelium. Moreover, it was observed that the gland recesses decreased, the neck regions of the glands were opened, the base regions were severely edematous and the blood capillaries had intense dilation and congestion. Severe PMNL infiltration was also noted in the connective tissue area around the vessel and adjacent to the gland bases in the samples belonging to this group (Fig 1B and Table 2). It was stated in the literature that I/R-induced ROS increase played a role in the formation of acute gastric mucosal lesions (Wada et al., 1996).
It was reported in a previous study that the I/R procedure increased gastric surface epithelial damage, edema, dilatation of capillaries, congestion and PMNL infiltration (Kuyrukluyildiz et al., 2021).
Similarly, Omayone et al., (2020)
reported that I/R induced gastric necrosis and inflammatory cell infiltration in the submucosa.
Fig 1: Histopathological analysis of stomach tissues of the study groups.
Table 2: Analysis results of histopathological scoring in stomach tissues of animal groups.
Desloratadine was a selective H1 receptor blocker and a non-sedating antihistaminic drug analyzed in terms of its protective effect upon oxidative gastric injury due to gastric I/R. Previous studies suggested that desloratadine not only had an antihistamine but also had an antioxidative effect (Tatar et al., 2015).
Furthermore, in the literature, there was information that desloratadine cleared O2
- and caused a decrease in ROS levels in patients with chronic idiopathic urticaria (Sadowska-Woda et al., 2010b).
In the literature review, no study was found investigating the effect of desloratadine on gastric I/R. However, the effect of desloratadine upon increased oxidative stress with kidney I/R was investigated by Kocaturk et al., (2020)
and it was suggested to prevent the increase of MDA. Similarly, our study also indicated that desloratadine suppressed the increase of MDA significantly compared to the animals in the I/R group (p
<0.001, Table 1). In addition, our analysis results showed that desloratadine inhibited the decrease of tGSH, SOD and CAT levels with I/R (p
<0.01, Table 1).Tatar et al., (2015)
. reported that desloratadine prevented the decrease of GSH and SOD levels in the allergic rhinitis model. Cassano et al., (2006)
also reported that desloratadine efficiently protected the SOD level against the harmfull effects of oxidative stress. It was found in a study carried out on children that desloratadine treatment normalized the decrease in CAT levels due to allergic rhinitis (Sadowska-Woda et al., 2010a).
Desloratadine was also documented to inhibit the synthesis and release of inflammatory mediators and cytokines (Cassano et al., 2006).
Previous studies also revealed that suppression of basal and histamine-stimulated NF-κB expression played a role in this inhibition (Kocaturk et al., 2020).
In our study, the increase in IL-6 levels in animals treated with I/R was inhibited by desloratadine, which is similar to the results of Jie et al., (2015)
Desloratadine attenuated histopathological injury as well as biochemical parameters. When the samples related to GIRD group treated with desloratadine were analyzed, it was determined that there was moderate edema in normal surface epithelium and mucous membranes and glandular bases, moderate level dilatation and congestion in blood vessels and moderate level PMNL infiltration in the areas around the blood vessel (Fig 1C and Table 2). Kocaturk et al., (2020).
also reported that desloratadine protected the kidney tissue from I/R injury. Tataret_al
(2015) revealed that desloratadine alleviated the oxidative stress induced histopathological injury in the submandibular gland.