Effects of tocilizumab and dexamethasone on the downregulation of proinflammatory cytokines and upregulation of antioxidants in the lungs in oleic acid-induced ARDS

Abstract

Background Acute respiratory distress syndrome (ARDS) is a life-threatening disease caused by the induction of inflammatory cytokines and chemokines in the lungs. There is a dearth of drug applications that can be used to prevent cytokine storms in ARDS treatment. This study was designed to investigate the effects of tocilizumab and dexamethasone on oxidative stress, antioxidant parameters, and cytokine storms in acute lung injury caused by oleic acid in rats. Methods Adult male rats were divided into five groups: the CN (healthy rats, n = 6), OA (oleic acid administration, n = 6), OA + TCZ-2 (oleic acid and tocilizumab at 2 mg/kg, n = 6), OA + TCZ-4 (oleic acid and tocilizumab at 4 mg/kg, n = 6), and OA + DEX-10 (oleic acid and dexamethasone at 10 mg/kg, n = 6) groups. All animals were euthanized after treatment for histopathological, immunohistochemical, biochemical, PCR, and SEM analyses. Results Expressions of TNF-α, IL-1β, IL-6, and IL-8 cytokines in rats with acute lung injury induced by oleic acid were downregulated in the TCZ and DEX groups compared to the OA group (P < 0.05). The MDA level in lung tissues was statistically lower in the OA + TCZ-4 group compared to the OA group. It was further determined that SOD, GSH, and CAT levels were decreased in the OA group and increased in the TCZ and DEX groups (P < 0.05). Histopathological findings such as thickening of the alveoli, hyperemia, and peribronchial cell infiltration were found to be similar when lung tissues of the TCZ and DEX groups were compared to the control group. With SEM imaging of the lung tissues, it was found that the alveolar lining layer had become indistinct in the OA, OA + TCZ-2, and OA + TCZ-4 groups. Conclusions In this model of acute lung injury caused by oleic acid, tocilizumab and dexamethasone were effective in preventing cytokine storms by downregulating the expression of proinflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-8. Against the downregulation of antioxidant parameters such as SOD and GSH in the lung tissues caused by oleic acid, tocilizumab and dexamethasone upregulated them and showed protective effects against cell damage.

Gossypin mitigates oxidative damage by downregulating the molecular signaling pathway in oleic acid‐induced acute lung injury

“…OA causes ALI/ARDS in rats by inducing the cytokine cascade by upregulating the expression of various proinflammatory cytokines, such as TNF‐α and IL‐1β. Similar to earlier studies, OA in our study synergistically elevated the expression of TNF‐α and IL‐1β in lung tissue 20,62,63 . These cytokines stimulate the production of additional proinflammatory cytokines and chemokines by encouraging the expression of IL‐6 and IL‐8 in other cells.…”

“…Similar to earlier studies, OA in our study synergistically elevated the expression of TNF-α and IL-1β in lung tissue. 20,62,63 These cytokines stimulate the production of additional which supports these PCR results. In our research, it was also discovered that the OA group had higher levels of IL-8 expression.…”

“…IL-6 has been proved to perform in conjunction with other proinflammatory cytokines to further the development of ALI 64. While OA raised TNF-α and IL-1β in lung tissue in our research it also increased IL-6 expression, which, as in earlier research, is positively correlated with the production of these proinflammatory cytokines 63,65. According to our research, GOS considerably reduced the expression of TNF-α, IL-1β, and IL-6 in the lungtissue of rats as compared to the OA group.…”

RETRACTED: Effects of tocilizumab and dexamethasone on proinflammatory cytokines and antioxidants in acute kidney injury caused by oleic acid-induced ARDS

“…Antioxidants such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) provide the necessary defenses against damage caused by oxidative stress.In the pathogenesis of ARDS, complex networks of cytokines and other proin ammatory compounds initiate and maintain the in ammatory response in the lungs [12]. In our previous study, it was determined that proin ammatory cytokines affect lung tissues in cases of ARDS [13]. Another key feature of ARDS is the complex in ammatory response that occurs in extrapulmonary organs.…”

Role of SARS-CoV-2-induced cytokine storm in multi-organ failure: Molecular pathways and potential therapeutic options

“…There is a wide range of adverse effects of corticosteroids, especially dexamethasone, which has been widely used for COVID-19. Hyperglycemia, fatty liver, insulin resistance, increased risk of diabetes, GI complications, headaches, skin acne, and dysregulated menstrual periods, are reported as their common effects [351] , [352] . Lastly, it is worth mentioning that despite the efficacy of herbal medicines, they also have adverse effects that clinicians should take into account.…”