Mitigative effects of chloroquine treatment against hypoxia-induced intestinal injury: a histological and immunohistochemical study

Abstract

Objective: Hypoxia has an important role in the disruption of intestinal mucosal integrity because of inflammation and apoptosis induced by inflammatory cytokines such as TNF-α (Tumor necrosis factor-alpha), IL-6 and IFN-y, and apoptotic regulatory proteins. Chloroquine (CLQ) is a drug used in the novel coronavirus disease (COVID-19) and is widely used for the treatment of many inflammatory diseases such as malaria and rheumatoid arthritis. In this study, we aimed to reduce the destructive effects of hypoxia-induced inflammation and apoptosis in the intestinal mucosa of rats with CLQ applications. Methods: For this purpose, a total of 24 Wistar Albino rats were randomly divided into three groups; Group I: Control group (n=8), Group II: Hypoxia (n=8) and Group III: Hypoxia + CLQ (n=8). The control group was housed in plexiglass cages to keep the oxygen levels at 10% levels for 28 days, while the hypoxia and hypoxia+CLQ groups were housed in a normal atmospheric environment (21% O2), and the hypoxia+CLQ group was administered CLQ at a dose of 50 mg/kg every day for 28 days. At the end of the experiment, the intestinal tissues of the experimental animals, were extracted under the anesthesia and they were sacrificed. Results: As a result of histopathological evaluations, it was determined that CLQ applications showed healing properties on the histopathological effects induced by hypoxia in the intestine. While an increase in TNF-α expression was observed in the hypoxia group, a statistically significant decrease was detected in the hypoxia+CLQ group. In addition, Bax expression was found to be statistically significantly lower in the hypoxia+CLQ group when compared to the hypoxia group. On the contrary, it was observed that Bcl-2 expression was statistically significantly increased in the hypoxia+CLQ group compared to the Hypoxia group. Conclusion: We observed that hypoxia causes significant damage to the intestinal mucosa and triggers a severe inflammation that drives cells to apoptosis. Considering the curative effects of chloroquine on the intestinal mucosa, we suggest that this anti-inflammatory drug has a potential to use clinically to alleviate the deleterious effects of hypoxia in the intestine.