RESUMO
Background: The world has been suffering from the Coronavirus Disease-2019 (COVID-19) pandemic since the end of 2019. The COVID-19-infected patients differ in the severity of the infection and the treatment response. Several studies have been conducted to explore the factors that affect the severity of COVID-19 infection. One of these factors is the polymorphism of the angiotensin converting enzyme 2 (ACE-2) and the type 2 transmembrane serine protease (TMPRSS2) genes since these two proteins have a role in the entry of the virus into the cell. Also, the ACE-1 regulates the ACE-2 expression, so it is speculated to influence the COVID-19 severity. Objective: This study investigates the relationship between the ACE-1, ACE-2, and TMPRSS2 genes single nucleotide polymorphism (SNPs) and the COVID-19 disease severity, treatment response, need for hospitalization, and ICU admission in Egyptian patients. Patients and Methods: The current study is an observational prospective, cohort study, in which 109 total COVID-19 patients and 20 healthy volunteers were enrolled. Of those 109 patients, 51 patients were infected with the non-severe disease and were treated in an outpatient setting, and 58 suffered from severe disease and required hospitalization and were admitted to the ICU. All 109 COVID-19 patients received the treatment according to the Egyptian treatment protocol. Results: Genotypes and allele frequencies among severe and non-severe patients were determined for ACE-1 rs4343, TMPRSS2 rs12329760, and ACE-2 rs908004. The GG genotype and the wild allele of the ACE-2 rs908004 and the mutant allele of the ACE-1 rs4343 were significantly more predominant in severe patients. In contrast, no significant association existed between the TMPRSS2 rs12329760 genotypes or alleles and the disease severity. Conclusion: The results of this study show that the ACE-1 and ACE-2 SNPs can be used as severity predictors for COVID-19 infection since also they have an effect on length of hospitalization.
RESUMO
Hemorrhagic cystitis (HC) is considered a fatal complication of cyclophosphamide (CP). Down-regulation of Nrf2 and induction of pro-inflammatory mediators are the main pathological factors. Recently, ameliorative potential of the angiotensin II (AII) type-1 (AT1) receptor blocker olmesartan (OLM) on oxidative stress and inflammatory cytokines was reported. The current study aims to investigate the possible protective effect of OLM on CP-induced HC in Wistar rats. The animals were divided into the control group (0.5% W/V carboxymethylcellulose, p.o.); OLM group (20 mg/kg, p.o., for 21 days); CP group (a single dose of 100 mg/kg, i.p.); and the remaining groups that received CP i.p. with oral OLM 5, 10 and 20 mg/kg for 21 days, respectively. The bladder tissue was collected for histopathology, immunohistochemistry, ELISA, Western blot, and oxidative stress assay. The OLM at doses of 10 and 20 mg/kg attenuated increase in TNF-α, IL-6, NF-kB, iNOS, and COX-2 induced by CP. Additionally, it up-regulated the Nrf2/HO-1 pathway, bladder GSH content, and CAT and SOD activities. The data indicated that OLM inhibited ROS-induced NF-kB, which caused inhibition of pro-inflammatory cytokines and activation of the Nrf2/HO-1 pathway. Hence, OLM holds great promise for preventing CP-induced HC.
