No abstract

Metformin is one of the oldest and commonly used blood sugar lowering drugs, having limited side effects and used as the first line treatment in patients suffering from diabetes mellitus. Moreover, various studies have emphasized on the anti-inflammatory and antioxidant role of metformin, with multiple mechanisms, which activation of AMPK by metformin has had a key role in many of them. During the searches on the internet websites of PubMed, Elsevier, Google Scholar, and Science Direct, 76 papers related to the anti-inflammatory and antioxidant role of metformin were selected and reviewed since 2003 to 2017. At the cellular level, metformin suppresses the inflammation in many cases and reduces or eliminates inflammatory factors mainly through dependent mechanisms and sometimes independent of AMPK at the cellular level and through other ways at the systematic levels. It is also effective in reducing the level of oxidative stress factors by regulating the antioxidant system of the cell. All evidence suggests the antioxidant and anti-inflammatory role of metformin in various conditions. Metformin can be an appropriate treatment option for many diseases, which inflammatory processes and oxidative stress play a role in their pathogenesis.

Studies have shown that SARS-CoV-2 has the ability to activate and mature proinflammatory cytokines in the body. Cytokine markers are a group of polypeptide signalling molecules that can induce and regulate many cellular biological processes by stimulating cell receptors at the surface. SARS-CoV-2 has been shown to be associated with activation of innate immunity, and an increase in neutrophils, mononuclear phagocytes, and natural killer cells has been observed, as well as a decrease in T cells including CD4+ and CD8. It is noteworthy that during the SARS-CoV-2 infection, an increase in the secretion or production of IL-6 and IL-8 is seen in COVID-19 patients along with a decrease in CD4+ and CD8+ and T cells in general. SARS-CoV-2 has been shown to significantly increase Th2, Th1/Th17 cells and antibody production in the body of patients with COVID-19. Specific immune profiles of SARS-CoV-2 infection can lead to secondary infections and dysfunction of various organs in the body. It has been shown that Interleukins (such as IL-1, IL-4, IL-6, IL-7, IL-10, IL-12, IL-17, and IL-18), IFN-γ, TNF-α,TGF-β and NF-κB play major roles in the body's inflammatory response to SARS-CoV-2 infection. The most important goal of this review is to study the role of inflammatory cytokines in COVID-19.

Diabetic neuropathy (DN) is characterized as Hyperglycemia activates thdisturbed nerve conduction and progressive chronic pain. Inflammatory mediators, particularly cytokines, have a determinant role in the pathogenesis of neuropathic pain. The activity of adenosine monophosphate protein kinase (AMPK), an energy charge sensor with neuroprotective properties, is decreased in diabetes. It has been reported that activation of AMPK reduces the systemic inflammation through inhibition of cytokines. In this study, we aimed to investigate the probable protective effects of AMPK on DN in a rat of diabetes. DN was induced by injection of streptozotocin (65 mg/kg, i.p.). Motor nerve conduction velocities (MNCV) of the sciatic nerve, as an electrophysiological marker for peripheral nerve damage, were measured. Plasma levels of IL-6, TNF-α, CRP were assessed as relevant markers for inflammatory response. Also, the expression of phosphorylated AMPK (p-AMPK) and non-phosphorylated (non-p-AMPK) was evaluated by western blotting in the dorsal root ganglia. Histopathological assessment was performed to determine the extent of nerve damage in sciatic nerve. Our findings showed that activation of AMPK by metformin (300 mg/kg) significantly increased the MNCV and reduced the levels of inflammatory cytokines. In addition, we showed that administration of metformin increased the expression of p-AMPK as well as decline in the level of non p-AMPK. Our results demonstrated that co-administration of dorsomorphin with metformin reversed the beneficial effects of metformin. In conclusion, the results of this study demonstrated that the activation of AMPK signaling pathway in diabetic neuropathy might be associated with the anti-inflammatory response.

Introduction: Renal dysfunction is caused by ischemia-reperfusion (I/R) injury, which is a common problem in kidney surgery or kidney transplantation. The human body consists of enormous complex antioxidant systems, which inquires adequate selenium (Se) absorption for normal physiologic function. It is known that Se has some antioxidant effects. Objectives: In the present research, effects of the Se on damages caused by I/R injury investigated. Materials and Methods: In this experimental research, four groups of rats (weighing 220±10 g) used, include control group, I/R group, healthy group treated with Se for two weeks, and I/R group with two-week Se treatment. On the test day, I/R was treated in both right and left renal arteries for 45 minutes and the reperfusion was done for 24 hours. Results: In I/R group, the amount of urea and serum creatinine (Cr) was an injury indicator of the kidney cells which showed a significant increase compared with the control group. When the treatment with Se significantly reduced these indicators, glutathione (GSH) enzyme levels reduced significantly in the second group and the enzyme levels increased due to Se treatment in the fourth group. Furthermore, malondialdehyde (MDA) enzyme levels increased in I/R group due to the Se treatment in the fourth group which was significantly reduced. In addition, the tissue damage was reduced in the fourth group compared with I/R group. Conclusion: Se has a protective effect against the I/R injury. This effect might be due to the antioxidant properties of Se.