Acute Hepatic Injury Associated with Acute Administration of Synthetic Cannabinoid XLR-11 in Mouse Animal Model.

The widespread recreational use of synthetic cannabinoids (SCs) has become a serious health issue. Reports of life-threatening intoxications related to SC consumption have markedly increased in recent years, including neurotoxicity, cardiotoxicity, nephrotoxicity, and hepatotoxicity. We investigated the impact of acute administration of the synthetic cannabinoid XLR-11 (3 mg/kg, i.p. for 5 consecutive days) on the liver in BALB/c mouse animal model. Using real-time quantitative RT-PCR, MDA assay, and TUNEL assay, we found consistent up-regulation of a variety of genes involved in oxidative stress (NOX2, NOX4, and iNOS), inflammation (TNF-α, IL-1ß, IL-6), and apoptosis (Bax) in the liver of XLR-11 treated mice compared to control mice. These finding were supported with an elevation of MDA levels and TUNEL positive cells in the liver of XLR-11 treated mice which further confirm increased oxidative stress and apoptosis, respectively. Histopathological analysis of the liver of XLR-11 treated mice confirmed pronounced hepatic necrosis associated with inflammatory cell infiltration. Furthermore, elevated ALT and AST serum levels were also identified in XLR-11 treated mice indicating possible liver damage. Overall, SC-induced hepatotoxicity seems to be mainly mediated by activated oxidative stress and inflammatory processes in the liver, but the specific mechanisms involved require further investigations. However, the present study shed light on the potential deleterious role of acute administration of SCs in the progression to acute hepatic injury which enhances our understanding of the adverse effect of SC consumption.

Effect of Estrogen and Progesterone Hormones on the Expression of Angiotensin II Receptors in the Heart and Aorta of Male Rats.

BACKGROUND: Activation of the Angiotensin II type 1 receptor (AT1R) has been implicated in the pathogenesis of the cardiovascular disease, while activation of Angiotensin II type 2 receptor (AT2R) leads to effects that are opposite to those mediated by AT1R. The interaction between female sex hormones and the renin-angiotensin system was proven to play an essential role in the pathological changes in the cardiovascular system. OBJECTIVES: To investigate the direct effect of estrogen and progesterone on arterial and cardiac AT1R and AT2R expression in vivo in male. METHOD: Male adult rats were assigned into four groups: Group 1 (control), group 2 (progesterone treated group; 10mg/kg), group 3 (estrogen treated group; 20µg/kg) and group 4 (progesterone; 10mg/kg + estrogen; 20µg/kg treated group). All treatments were administrated subcutaneously every second day for 21days. RESULTS: Estrogen treatments increase the left ventricle (LV) protein expression of AT1R, and progesterone treatment decreased the LV protein expression of AT2R. In the aorta, estrogen treatment increased the mRNA expression levels of AT1R, while progesterone treatment increased the AT2R mRNA expression levels. Estrogen treatment decreases the LV and aortic endothelial nitric-oxide synthase (eNOS) mRNA levels while progesterone treatments decrease the LV eNOS mRNA levels but increase the aortic eNOS mRNA levels. The serum angiotensin II levels were increased by estrogen treatment only. CONCLUSION: Both estrogen and progesterone treatments appear to have a harmful effect on the male rat hearts, possibly by increasing the protein expression of AT1R (for estrogen), decrease the protein and mRNA expression of AT2R (for progesterone), and decrease the eNOS mRNA levels (for both). However, it seems that progesterone but not estrogen exerts a vascular protective effect in males.

Effect of gold nanoparticles treatment on the testosterone-induced benign prostatic hyperplasia in rats.

Background: Gold nanoparticles (AuNps) are promising agents for prostate cancer therapy. Herein, the in vivo effects of 20 and 50 nm sized AuNps on experimentally induced benign prostatic hyperplasia (BPH) was examined. Materials and methods: Adult male rats were divided into four groups (n=6-8 each). A negative control group and three groups were injected daily with testosterone (3 mg/kg/subcutaneously) to induce BPH. Animals receiving testosterone were randomized to untreated BPH group and two BPH groups which were treated intraperitoneally with 20 and 50 nm AuNps (5 mg/kg/daily) in addition to testosterone. After three weeks, histopathological changes and serum levels of testosterone and dihydrotestosterone (DHT) were analyzed. In addition, the prostate tissue levels of transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor-a (VEGF-A) and interleukin-6 (IL-6) were measured using ELISA. Results: There were significant increases in the prostate weight/body weight ratio, serum testosterone and DHT and in the prostate tissue content of TGF-ß1, IL-6 and VEGF-A in the untreated BPH group. histological examination showed morphological abnormalities with more proliferation in the glandular epithelial and stromal area and with abundant epithelial papillary folds in the BPH group. Simultaneous administration of 50 nm AuNps with testosterone tended to increase the prostate weight/body weight ratio and increase the tissue level of IL-6 in compared to the BPH group. Conversely, treatment with 20 nm AuNps significantly reduced the elevated tissue content of TGF-ß1, IL-6, and VEGF-A. Histopathological examination also showed that 20 nm but not the 50 nm AuNps administration ameliorates testosterone-induced prostatic hyperplasia. Conclusions: In experimentally induced BPH, AuNps can inhibit the progression of BPH in a size-dependent manner. while 20 nm AuNps ameliorate BPH by its inhibitory effects on the prostatic cell proliferation, inflammation and angiogenesis, the 50 nm AuNps could potentially exacerbate the development of BPH in rats, mainly through enhancing the inflammatory process.