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Gonzalez-Mariscal, I.

Publications and source records attributed to Gonzalez-Mariscal, I..

2 recordsLinked to original sources
bioRxiv2020

Abnormal Cannabidiol protects pancreatic beta cells in mouse models of experimental Type 1 diabetes

Background and PurposeThe atypical cannabinoid Abn-CBD was reported to improve the inflammatory status in preclinical models of several pathologies including autoimmune diseases. However, its potential for autoimmune diabetes, i.e. type 1 diabetes (T1D), is unknown. Experimental ApproachWe used two mouse models of T1D, streptozotocin (STZ)-injected and non-obese diabetic (NOD) mice. Eight-to-ten-week-old male C57Bl6/J mice were pre-treated with Abn-CBD (1mg/kg of body weight) or vehicle for 1 week, following STZ treatment, and euthanized 1 week later. Six-week-old female NOD mice were treated with Abn-CBD (0.1-1mg/kg) or vehicle for 12 weeks and then euthanized. Blood, pancreas, pancreatic lymph nodes and circulating T cells were collected and processed for analysis. Glycemia was also monitored. Key ResultsAbn-CBD decreased circulating proinflammatory cytokines, ameliorated islet inflammation and the autoimmune attack, showing a 2-fold decrease in CD8+ T cells infiltration and reduced Th1/Th2 ratio in pancreatic lymph nodes of STZ-injected mice. Mechanistically, Abn-CBD reduced intra-islet phospho-NF-{kappa}B and TXNIP. Concomitant reduction of islet cell apoptosis and intra-islet fibrosis were observed in Abn-CBD pre-treated mice compared to vehicle. In NOD mice, Abn-CBD reduced the expression of Ifng, Il21, Tnfa and Il10 while increased Il4 in circulating CD4+ T cells compared to vehicle, reducing the severity of insulitis and improving glucose tolerance. Conclusion and ImplicationsAltogether, we found that Abn-CBD reduces intra-islet inflammation and delays the progression of insulitis in mouse models of T1D, preserving healthy functional islets. Hence, Abn-CBD and related compounds emerge as new candidates to develop pharmacological strategies to treat early stages of T1D. WHAT IS ALREADY KNOWN- Phytocannabinoids such as cannabidiol (CBD) have anti-inflammatory and glucose-lowering properties - The CBD derivative Abn-CBD ameliorates inflammation in various diseases and modulates beta cell function WHAT THIS STUDY ADDS- Abn-CBD reduces systemic and pancreatic inflammation in mice models of type 1 diabetes - Abn-CBD prevents beta cell damage and loss during type 1 diabetes onset CLINICAL SIGNIFICANCE- Synthetic cannabinoids emerge as potential treatment for type 1 diabetes

pharmacology and toxicology↗
bioRxiv2020

Δ9-Tetrahydrocannabinolic Acid markedly alleviates liver fibrosis and inflammation in murine models of chemically- and obesity-induced liver injury

BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, and it is closely associated to obesity, type 2 diabetes mellitus, and dyslipidemia. Hepatocellular stellate cells (HSCs) activation by oxidative stress and inflammation is the hallmark of liver fibrosis and leads to cirrhosis and liver failure resistant to pharmacological management. Cannabinoids have been suggested as a potential therapy for liver fibrosis, prompting us to explore the antifibrotic and anti-inflammatory effects of {Delta}9-THCA-A, a major non-psychotropic cannabinoid from Cannabis sativa L., in animal models of NAFLD. MethodsNon-alcoholic liver fibrosis was induced in mice by CCl4 treatment or, alternatively, by 23-week high fat diet (HFD) feeding. {Delta}9-THCA was administered daily intraperitoneally during the CCl4 treatment or during the last 3 weeks in HFD-fed mice. Liver fibrosis and inflammation were assessed by immunochemistry and qPCR. Blood glucose and plasma insulin, leptin and triglyceride levels were measured in HFD mice. Results{Delta}9-THCA significantly attenuated CCl4-induced liver fibrosis and inflammation and reduced T cell and macrophage infiltration. Mice fed HFD for 23 weeks developed severe obesity (DIO), fatty liver and marked liver fibrosis, accompanied by immune cell infiltration. {Delta}9-THCA, significantly reduced body weight and adiposity, improved glucose tolerance, and drastically attenuated DIO-induced liver fibrosis and immune cell infiltration. Conclusions{Delta}9-THCA prevents liver fibrogenesis in vivo, providing a rationale for additional studies on the medicinal use of this cannabinoid, as well as cannabis preparations containing it, in the treatment of liver fibrosis and the management of NAFLD.

pharmacology and toxicology↗