ABSTRACT
The innate immune system is a primary protective line in our body. It confers its protection through different pattern recognition receptors (PRRs), especially toll like receptors (TLRs). Toll like receptor 9 (TLR9) is an intracellular TLR, expressed in different immunological and non-immunological cells. Release of cellular components, such as proteins, nucleotides, and DNA confers a beneficial inflammatory response and maintains homeostasis for removing cellular debris during normal physiological conditions. However, during pathological cellular damage and stress signals, engagement between mtDNA and TLR9 acts as an alarm for starting inflammatory and autoimmune disorders. The controversial role of TLR9 in different diseases baffled scientists if it has a protective or deleterious effect after activation during insults. Targeting the immune system, especially the TLR9 needs further investigation to provide a therapeutic strategy to control inflammation and autoimmune disorders.
Subject(s)
Autoimmune Diseases , Toll-Like Receptor 9 , DNA, Mitochondrial , Humans , Nucleotides , Toll-Like Receptor 9/genetics , Toll-Like ReceptorsABSTRACT
AIM: Acute kidney injury (AKI) is a sudden incident that is linked with a high lethality rate commonly due to distant organ injury. This study aims to explore the role of standardized Boswellia serrata (containing 35 % boswellic acid) in attenuating kidney and liver damage in a model of rats with renal insult. MAIN METHODS: Sprague-Dawley rats, exposed to renal injury via ischemia-reperfusion model, were administered a daily regimen of 1000 or 2000 mg/kg Boswellia for seven days then rats were sacrificed on day eight. Alanine aminotransferase, aspartate aminotransferase, serum creatinine and blood urea nitrogen, were assayed. TLR9, oxidative stress markers; namely MDA and GSH, inflammatory cytokines; namely, IL-6, IL-1ß, and TNF-α, as well as NF-κB were also measured. KEY FINDINGS: Renal ischemia-reperfusion injury (IRI) impaired renal and liver function significantly, but Boswellia attenuated this impairment in a dose-dependent fashion. Histopathological assessment of kidney and liver confirmed that Boswellia decreased damage severity. A marked increase in TLR9, NF-κB, IL-6, IL-1ß, TNF-α, and MDA besides decreased GSH levels were observed in the kidney and liver after renal IRI. Boswellia attenuated increases in TLR9, NF-κB, IL-1ß, TNF-α, and IL-6 and boosted antioxidant defences via decreasing MDA and increasing GSH in kidney and liver. Anti-inflammatory and antioxidant effects of Boswellia were mostly comparable to those of silymarin. SIGNIFICANCE: We conclude that the anti-inflammatory and antioxidant effects of Boswellia could be beneficial in ameliorating kidney and liver damage after AKI and that TLR9 might be the connection that signals liver injury in response to renal damage.
Subject(s)
Acute Kidney Injury , Boswellia , Reperfusion Injury , Acute Kidney Injury/drug therapy , Acute Kidney Injury/etiology , Acute Kidney Injury/metabolism , Animals , Anti-Inflammatory Agents/therapeutic use , Antioxidants/metabolism , Boswellia/metabolism , Interleukin-6/metabolism , Ischemia/metabolism , Kidney/metabolism , Liver/metabolism , NF-kappa B/metabolism , Rats , Rats, Sprague-Dawley , Reperfusion , Reperfusion Injury/complications , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Toll-Like Receptor 9/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
OBJECTIVE: To systematically search the literature and to summarize current evidence pertaining to the epidemiology of SCI in the MENA region incidence, gender, age, type of the injury and etiology of the injury. METHODS: Embase, PubMed, Scopus, Web of Science and EBSCOhost were systematically searched from their dates of inception till July 2017 for English and non-English language articles. Also, regional databases were searched. Data were extracted from eligible articles and pooled under the random effect model using R. References of the included articles were also screened for potentially relevant studies. RESULTS: We identified 29 articles from seven countries in the MENA region (Turkey, Iran, Saudi Arabia, Egypt, Jordan, Kuwait and Qatar). The mean age of the cases at time of injury was 31.32 (95% CI: 28.74-33.91). The random pooled annual incidence of TSCI per million was 23.24 (95% CI: 5.64-49.21). Pooled proportion of male gender was 77% (95% CI 73-80%) of the cases. Complete paraplegia was the most common type of injury. Thoracic level injury predominated. Also, the most commonly affected age group was 20-29 then 30-39. Motor vehicle accidents were found to be the leading cause of injury, then falls, gunshot, violence and sports. Further meta-regression analysis showed no association between age and etiology of the injury. CONCLUSION: This review shows lack of evidence about SCI in most countries of the MENA region. More epidemiological studies are needed.
