ABSTRACT
Aims: In numerous cases, patients with inflammatory bowel diseases (IBDs) are refractory to standard treatment. Sirolimus (SIR) and tacrolimus (TAC) are immunosuppressant drugs with encouraging outcomes. However, they have side effects causing limitations in their use. Metformin (MET), which is an antidiabetic drug, has promising anti-inflammatory effects. Thus, this study aimed to validate the effect of the concomitant administration of MET and SIR or TAC in the management of experimentally induced colitis.Study Design:Dextran sulphate (DSS) induced colitis model was used Methodology:Colitis was induced by administering 5% DSS in water twice daily via oral gavage for 9 days. MET 200 mg/kg alone or in combination with SIR 1 mg/kg or TAC 1 mg/kg was started on day 7 and was continuously administered for 12 days. Then, samples of distal colon tissues were collected for histopathological and immunohistochemistry staining. Then, the pro-inflammatory cytokine, tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-17A levels in tissue homogenates were measured.Results:MET,SIR or TAC significantly attenuated the effect of DSS and the levels of all pro-inflammatory cytokines. Moreover, adding MET reinforces the effect of SIR and TAC. Conclusion:MET had a strong anti-inflammatory effect against DSS-induced colitis. Hence, it could be a promising adjuvant therapy in the management of IBDs. The effect was mediated, in part, by inhibiting NF-κB activation. However, the results of this study must be further validated and translated to clinical implications
ABSTRACT
After the global pandemic of the new coronavirus, its rapid spreadand many victims, it is necessary to find an effective vaccine or drugs to overcome it. Most specialists consider that repositioning somemedications is the best, fastestand most reliable option for treating patients with the new coronavirus without delay. One of these drugs was an old antimalarial drug, hydroxychloroquine. The current review aimed to explore its potential mechanism, as well as its pharmacokinetics and toxicity, in an attempt to suggest a treatment protocol for its use in treating the COVID-19 virus effectively and safely. This study reviewed the published references on the popular search engines as well as the reference books regarding the pharmacological effects of HCQ.The results of this study suggested the following practical guidelines to optimize HCQ efficacy and safety in the management of COVID-19. HQC should be used as early as possible, i.e., once the viral infection is confirmed or suspected. A loading dose is recommended to be given in 3-4 divided doses to minimize cardiac toxicity. Maintenance daily dose (divided into two doses), should be continued until complete remission. Precautions,drug-interaction, contraindications, variable metabolic pathways in the particular population should be considered. This study suggests more clinical trials regarding the use of HCQ in the management of early identified COVID-19 patients under close medical observation to minimize HCQ cardiac toxicity