Empagliflozin protective effects against cisplatin-induced acute nephrotoxicity by interfering with oxidative stress and inflammation in Wistar rats.

Cisplatin (Cis) is a platinum-based antineoplastic drug used in various types of cancers. This drug can induce nephrotoxicity as a cause of acute kidney injury (AKI) by inducing oxidative stress and inflammation. Empagliflozin (Empa) is a newly developed inhibitor of sodium-glucose cotransporter-2 (SGLT2) approved as an antidiabetic medication for patients with type 2 diabetes mellitus. In addition to its blood glucose-lowering effect, Empa has been shown to exert anti-inflammatory and anti-oxidant properties. The current study aimed to investigate the protective effects of Empa on Cis-induced nephrotoxicity in rats. Male Wistar albino rats were divided into five groups, each of six rats: Sham group (received vehicle for 7 days), Control group (received vehicle for 7 days and Cis injection on day 2), Cis + Empa10 (received 10mg/kg Empa for 7 days and Cis injection on day 2), Cis + Empa30 (received 30mg/kg Empa for 7 days and Cis injection on day 2) and, Empa 30 (received 30mg/kg Empa for 7 days). One day after the last injection in each group, rats were weighed and then sacrificed to analyze the hematological, biochemical, and histological parameters. Cis markedly increased levels of inflammatory parameters such as renal tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and myeloperoxidase (MPO) activity. Notably, malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine levels were enhanced after Cis administration. Also, the chemotherapeutic agent significantly reduced antioxidant indicators such as renal catalase (CAT), glutathione peroxidase (GpX), and superoxide dismutase (SOD). Furthermore, histopathological examinations also revealed severe renal damage following Cis treatment which was improved by Empa administration. Empa treatment at both doses (10 mg/kg and 30 mg/kg) reversed Cis-induced changes in all the above renal parameters. In conclusion, Empa has protective effects on Cis-induced nephrotoxicity by inhibition of oxidative stress and inflammation.

Therapeutic effects of anti-diabetic drugs on traumatic brain injury.

AIMS: In this narrative review, we have analyzed and synthesized current studies relating to the effects of anti-diabetic drugs on traumatic brain injury (TBI) complications. METHODS: Eligible studies were collected from Scopus, Google Scholar, PubMed, and Cochrane Library for clinical, in-vivo, and in-vitro studies published on the impact of anti-diabetic drugs on TBI. RESULTS: Traumatic brain injury (TBI) is a serious brain disease that is caused by any type of trauma. The pathophysiology of TBI is not yet fully understood, though physical injury and inflammatory events have been implicated in TBI progression. Several signaling pathways are known to play pivotal roles in TBI injuries, including Nuclear factor erythroid 2-related factor 2 (Nrf2), High mobility group box 1 protein/Nuclear factor kappa B (HMGB1/NF-κB), Adiponectin, Mammalian Target of Rapamycin (mTOR), Toll-Like Receptor (TLR), Wnt/ß-catenin, Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT), Nod-like receptor protein3 (NLRP3) inflammasome, Phosphoglycerate kinase 1/Kelch-like ECH-associated protein 1 (PGK1/KEAP1)/Nrf2, and Mitogen-activated protein kinase (MAPK) . Recent studies suggest that oral anti-diabetic drugs such as biguanides, thiazolidinediones (TZDs), sulfonylureas (SUs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), dipeptidyl peptidase-4 inhibitors (DPPIs), meglitinides, and alpha-glucosidase inhibitors (AGIs) could have beneficial effects in the management of TBI complications. These drugs may downregulate the inflammatory pathways and induce antioxidant signaling pathways, thus alleviating complications of TBI. CONCLUSION: Based on this comprehensive literature review, antidiabetic medications might be considered in the TBI treatment protocol. However, evidence from clinical trials in patients with TBI is still warranted.

Superoxide dismutase: a key target for the neuroprotective effects of curcumin.

Over the past few years, the prevalence of neurodegenerative diseases (NDD) has increased dramatically. The community health system is burdened by the high healthcare costs associated with NDD. Superoxide dismutase (SOD) is a type of metalloenzyme that possesses a distinct characteristic of protecting the body from oxidative stress through antioxidants. In this way, SOD supplementation may activate the endogenous antioxidant mechanism in various pathological conditions and could be used to neutralize free radical excess. Several factors are responsible for damaging DNA and RNA in the body, including the overproduction of reactive species, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS). Excessive ROS/RNS have deleterious effects on mitochondria and their metabolic processes, mainly through increased mitochondrial proteins, lipids and DNA oxidation. Studies have shown that oxidative stress is implicated in the etiology of many diseases, including NDD. It is thought that anti-inflammatory compounds, particularly phytochemicals, can interfere with these pathways and regulate inflammation. Extensive experimental and clinical research has proven that curcumin (Cur) has anti-inflammatory and anti-neurologic properties. In this review, we have compiled the available data on Cur's anti-inflammatory properties, paying special attention to its therapeutic impact on NDD through SOD.

Sodium Glucose Transporter-2 Inhibitors (SGLT2Is)-TLRs Axis Modulates Diabetes.

Diabetes affects millions of people worldwide and is mainly associated with impaired insulin function. To date, various oral anti-diabetic drugs have been developed, of which, the sodium glucose transporter-2 inhibitors (SGLT2Is) are of the most recent classes that have been introduced. They differ from other classes in terms of their novel mechanism of actions and unique beneficial effects rather than just lowering glucose levels. SGLT2Is can protect body against cardiovascular events and kidney diseases even in non-diabetic individuals. SGLT2Is participate in immune cell activation, oxidative stress reduction, and inflammation mediation, thereby, moderating diabetic complications. In addition, toll like receptors (TLRs) are the intermediators of the immune system and inflammatory process, thus it's believed to play crucial roles in diabetic complications, particularly the ones that are related to inflammatory reactions. SGLT2Is are also effective against diabetic complications via their anti-inflammatory and oxidative properties. Given the anti-inflammatory properties of TLRs and SGLT2Is, this review investigates how SGLT2Is can affect the TLR pathway, and whether this could be favorable toward diabetes.

Pharmacological activities of turmerones.

Turmerones are major bioactive compounds of Curcuma species with several beneficial pharmacological activities. In addition, various in vivo and in vitro studies noted that turmerones could affect different cytokines, metabolic pathways, and targets. Turmerones will have the potential to be a candidate agent to lessen many pathological and immunological conditions as a result of these pharmacological activities. In this review, we provided information about the pharmacological actions of turmerones using search engines such as PubMed, Google Scholar, Scopus, and Web of Science.

IDO/Kynurenine; novel insight for treatment of inflammatory diseases.

Inflammation and oxidative stress play pivotal roles in pathogenesis of many diseases including cancer, type 2 diabetes, cardiovascular disease, atherosclerosis, neurological diseases, and inflammatory diseases such as inflammatory bowel disease (IBD). Inflammatory mediators such as interleukins (ILs), interferons (INF-s), and tumor necrosis factor (TNF)-α are related to an extended chance of inflammatory diseases initiation or progression due to the over expression of the nuclear factor Kappa B (NF-κB), signal transducer of activators of transcription (STAT), nod-like receptor family protein 3 (NLRP), toll-like receptors (TLR), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways. These pathways are completely interconnected. Theindoleamine 2,3 dioxygenase (IDO) subset of the kynurenine (KYN) (IDO/KYN), is a metabolic inflammatory pathway involved in production of nicotinamide adenine dinucleotide (NAD + ). It has been shown that IDO/KYN actively participates in inflammatory processes and can increase the secretion of cytokines that provoke inflammatory diseases. Data were extracted from clinical and animal studies published in English between 1990-April 2022, which were collected from PubMed, Google Scholar, Scopus, and Cochrane library. IDO/KYN is completely associated with inflammatory-related pathways, thus leading to the production of cytokines such as TNF-α, IL-1ß, and IL-6, and ultimately development and progression of various inflammatory disorders. Inhibition of the IDO/KYN pathway might be a novel therapeutic option for inflammatory diseases. Herein, we gathered data on probable interactions of the IDO/KYN pathway with induction of some inflammatory diseases.