Ibuprofen Attenuates Cardiac Fibrosis in Streptozotocin-Induced Diabetic Rats

Abstract

Objective: To investigate the effects of ibuprofen on cardiac fibrosis in a rat model of type 1 diabetes. Methods: The diabetic model was established by injecting streptozotocin into the rats. Then, ibuprofen or pioglitazone was given by gavage for 8 weeks. The cardiac fibrosis was assessed, and the major components of the renin-angiotensin system, the transforming growth factor β₁ (TGF-β₁) and the mammalian target of rapamycin (mTOR), were evaluated by histopathological, immunohistochemical, Western blot analysis or ELISA assay. Results: Obvious cardiac fibrosis was detected in the diabetic group and was alleviated by ibuprofen treatment. Angiotensin-converting enzyme (ACE), angiotensin (Ang) II and AngII type 1 receptor (AT1-R) levels were higher, and ACE2, Ang(1-7) and Mas receptor (Mas-R) were lower in the diabetic group. The ratio of ACE to ACE2 was raised in the diabetic group. All these changes were ameliorated by ibuprofen. TGF-β₁ and mTOR were raised in the hearts of the diabetic group and were attenuated by ibuprofen treatment. There was no significant difference between the ibuprofen and the pioglitazone groups. Conclusion: Ibuprofen could ameliorate the cardiac fibrosis in diabetic rats by reduction of the ACE/AngII/AT1-R axis and enhancement of the ACE2/Ang(1-7)/Mas-R axis, leading to a decrease in TGF-β₁ and mTOR.

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19

“…These studies provided key findings on molecular mechanisms involved in the viral infection and the induction of inflammation by SARS-CoV. Few data on the inhibitory effects of Ibuprofen on ACE2 were reported in animal models [62].…”

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“…The role of NSAIDs in the course of viral infections is still controversial. Ibuprofen has been demonstrated to induce an overexpression of ACE2 when used in diabetic rats [50] and this effect might theoretically increase the susceptibility and worsen the clinical course of COVID -19 infection in treated patients [15]. In addition, the use of both NSAIDs and acetaminophen could be associated with a masking of the fever rise during COVID-19, resulting in a delay in diagnosis and proper management of the infection.…”

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“…Despite these small studies suggesting the benefit of drugs acting on RAS pathway, there is some data, albeit scarce, from animal models and human studies that treatment with ACE inhibitors and ARB could causeup regulation of ACE2 [24]. Ibuprofen and thiazolidinediones have also been shown to do the same [25,26]. Increased expression of ACE2 could theoretically increase the risk of infection with SARS CoV-2.…”