Potential Hepatoprotective Effects of Irbesartan, an Accessible Angiotensin II Receptor Blocker, Against Cisplatin-Induced Liver Injury in a Rat Model.

Objectives: Drug-induced liver injury is a common adverse reaction that frequently occurs with chemotherapeutic agents, such as cisplatin (CIS). This study seeks to enhance our understanding of drug actions and their associated adverse effects by examining the toxicity of CIS on rat liver tissue. We aimed to investigate the potential hepatoprotective effects of irbesartan (IRB), an easily accessible angiotensin II receptor blocker, in mitigating CIS-induced hepatotoxicity. Materials and Methods: Wistar albino rats were divided into four groups. These groups included a control group [saline, per oral (p.o.)] for seven days, and 1 mL saline intraperitoneal [(i.p.) on the fourth day]; a CIS group (1 mL saline for seven days and 7.5 mg/kg CIS i.p. on the fourth day); a CIS + IRB group (IRB: 50 mg/kg p.o. for seven days and 7.5 mg/kg CIS i.p. on the fourth day), and an IRB group (50 mg/kg IRB p.o. for seven days). The effect of IRB on interleukin-1 beta (IL-1ß) and caspase 3 levels was evaluated by immunohistochemical analysis, and its effects on mRNA expression levels of CCAAT/enhancer-binding protein homologous protein (CHOP) and immunoglobulin-heavy-chain-binding protein (BiP) were tested by quantitative real-time polymerase chain reaction. Results: IRB administration mitigated CIS-induced liver toxicity by inhibiting endoplasmic reticulum (ER) stress. Specifically, this drug reduced the mRNA expression of ER stress markers, including CHOP and BiP. In addition, IRB treatment decreased oxidative stress, inflammatory responses, and apoptotic markers. Conclusion: These findings suggest that IRB is a promising therapeutic option for preventing CIS-induced liver injury, potentially by modulating ER stress-related pathways.

The effect of Vortioxetine on the NLRP3 pathway and microglial activity in the prefrontal cortex in an experimental model of depression.

BACKGROUND: Increasing evidence suggests that early life stress (ELS) and neuroinflammation are associated with the pathophysiology of depression. The purpose of this study was to determine the effects of Vortioxetine (VOR), a novel antidepressant, on ELS-induced behavioral changes and neuroinflammation. METHOD: Wistar Albino 4-week-old male rats were divided into four groups: control; chronic unpredictable stress (CUMS), VOR, CUMS + VOR. Neurobehavioral assessment was performed on the first, 21st, and 42nd days. RT-PCR was used to detect the expression of P2X7, NLRP3, IL1ß, IL18 in the prefrontal cortex. To assess the microglial activities of the prefrontal cortex, immunohistochemically stained CD68, and leukocyte common antigen (LCA) preparations were scanned with Manual WSI software, Basler camera, and scored. RESULT AND DISCUSSION: Exposure to CUMS was associated with depression and anxiety-like behaviors, and administration of VOR led to improvement in these behaviors. NLRP3, IL-1ß, and IL-18 were shown to be upregulated in the prefrontal cortex of CUMS rats, while their high expression was inhibited by VOR treatment. CD68 and LCA expressions were significantly higher in the CUMS group compared to the other groups. CONCLUSION: According to these results, it may be considered that NLRP3 inflammasome-associated neuroinflammatory response and microglial activation may play a role in the etiopathogenesis of ELS.

The role of raftlin in the pathogenesis of chronic rhinosinusitis with nasal polyps.

PURPOSE: The aim of this study was to investigate the possible role of raftlin (RFTN) in chronic rhinosinusitis with nasal polyps (CRSwNP). There is no study in the literature investigating the role of RFTN in the pathogenesis of CRSwNP. METHODS: The present study was designed as a case-control study and conducted between 25.09.2020 and 01.01.2022. CRSwNP and control groups were formed in the study. Serum and tissue samples were taken from each patient in the study and their RFTN levels were measured. While nasal polyps were used for tissue samples in the CRSwNP group, middle meatus mucosa obtained during concha bullosa surgery was used in the control group. RESULTS: The control group included 31 patients (8 female, 23 male) and the CRSwNP group included 49 patients (14 female, 35 male). The mean age of the control group was 40.42 ± 9.99 years, while the mean age of the CRSwNP group was 43.47 ± 10.19 years. When the groups are compared in terms of gender and age, there were no statistically significant differences (p = 0.78, p = 0.19, respectively). The serum RFTN levels in the control and CRSwNP groups were 7.85 ± 10.87 ng/ml, and 7.02 ± 8.59 ng/ml, respectively (p = 0.45). The tissue RFTN levels in the control group and CRSwNP group were 87.15 ± 69.91 ng/ml, and 66.50 ± 17.10 ng/ml, respectively (p = 0.04, statistically significant). CONCLUSION: RFTN deficiency in nasal polyp tissue may be one of the reasons for the development of CRSwNP. Further studies are needed to elucidate the role of RFTN in CRSwNP.