jwh-133 and Reperfusion-Injury

Uterus transplantation is a complex surgical procedure. Uterine ischemia/reperfusion (IR) damage occurring in this process may cause loss of function in the uterus. Cell damage must be prevented for a healthy uterine function and successful transplantation. Cannabinoids, with their increasing clinical use, are substances with strong anti-inflammatory and antioxidative effects and have a role in immune system regulation. However, their efficacy in uterine IR damage is still unknown. This study provides information on the potential applications cannabinoids agonist JWH-133 in uterine IR damage and, hence, in the transplant process.. Rats were divided into 4 groups (n = 8), performed uterine IR, and treated 2 groups with JWH-133. After anesthesia, ischemia was applied for 1 h to the uterus while reperfusion was applied for 3 h. After the experiment, malondialdehyde (MDA) levels and phosphorylated nuclear factor-kappa B (p-NF-κB) expression were examined in the tissue samples. Also, cell damage was evaluated by histopathological imaging and TUNEL staining.. In the uterine IR group, NF-κB expression and MDA levels were detected at high levels. Histopathological examinations and TUNEL staining revealed extensive cell damage. On the other hand, in groups treated with JWH-133, dose-dependent NF-κB expression and MDA levels decreased (p < 0.05). Depending on the dose, the rate of surviving cells increased in TUNEL staining results.. The results showed that JWH-133 was effective in reducing uterine IR damage. Cannabinoids may be a new alternative that may be used in the transplantation process in the future.

Topics: Animals; Apoptosis; Cannabinoid Receptor Agonists; Cannabinoids; Cell Survival; Disease Models, Animal; Female; In Situ Nick-End Labeling; Injections, Intraperitoneal; Malondialdehyde; NF-kappa B; Protective Agents; Rats, Wistar; Receptor, Cannabinoid, CB2; Reperfusion Injury; Uterus

We investigated the efficacy of activated cannabinoid 2 receptors for alleviating ovarian ischemia-reperfusion injury in rats. Female Wistar albino rats were divided randomly into six groups: ischemia-reperfusion (IRG); ischemia-reperfusion + 0.2 mg/kg JWH-133 (JIRG1), ischemia-reperfusion + 1 mg/kg JWH-133 (JIRG2); ischemia-reperfusion + 5 mg/kg JWH-133 (JIRG3); solvent control, and sham control. Ovarian ischemia was established for 3 h followed by reperfusion for 3 h. Ovarian tissue was investigated using histology, immunohistochemistry and biochemistry. Administration of JWH-133 synthetic cannabinoid reduced nuclear factor kappa-B immunoreactivity as well as TUNEL positivity scores and malondialdehyde levels. These reductions were significant in all cases except for the malondialdehyde levels in the 1 mg/kg JWH-133 group. Activation of cannabinoid 2 receptors by JWH-133 reduced ovarian ischemia-reperfusion injury due to its antioxidant and anti-inflammatory effects.

Topics: Animals; Cannabinoids; Female; Malondialdehyde; Rats; Rats, Wistar; Receptors, Cannabinoid; Reperfusion Injury

Cannabinoid-2 receptor (CB2R) plays an important role in the cascading inflammation following ischemic injury. The toll-like receptors 4 (TLR4)/matrix metalloproteinase 9 (MMP9) signal pathway is involved in blood-brain barrier dysfunction induced by ischemia stroke. The aim of this study is to investigate the roles of exogenous activation of CB2R on attenuating neurological deficit and blood-spinal cord barrier (BSCB) disruption during rat spinal cord ischemia reperfusion (I/R) injury, through modulation of the TLR4/MMP9 axis.. Animals were intraperitoneally pretreated with TLR4 inhibitor TAK-242, CB2R agonist JWH-133 with or without CB2R antagonist AM630, or equivalent volume of vehicle 1 h before undergoing 14-min occlusion of descending aorta or sham operation. One, two, three, and 7 days after reperfusion, hindlimb locomotor function was evaluated with Basso, Beattie, and Bresnahan (BBB) Locomotor Scale, BSCB integrity was detected by measurement of Evans blue (EB) extravasation and spinal cord edema. The protein expression levels of CB2R, tight junction protein Zonula occluden-1 (ZO-1), TLR4, MMP9, MyD88, NF-κB p65, and NF-κB p-p65 were determined by western blot. The MMP9 activity was analyzed by gelatin zymography. Double immunofluorescence staining was used to identify the perivascular localization of CB2R, TLR4, MMP9, and reactive astrocytes, as well as the colocalization of CB2R, TLR4, and MMP9 with reactive astrocytes.. JWH-133 pretreatment attenuated hindlimb motor functional deficit and BSCB leakage, along with preventing downregulation of ZO-1 and upregulation of TLR4/MMP9, similar to the effects of TAK-242 preconditioning. JWH-133 or TAK-242 pretreatment reduced the perivascular expression of TLR4/MMP9 and reactive astrocytes following injury. JWH-133 pretreatment also downregulated MyD88/NF-κB level, MMP9 activity, and the astrocytic TLR4/MMP9 after I/R injury.. Exogenous activation of CB2R by JWH-133 attenuated neurological deficit and BSCB disruption after spinal cord I/R injury via inhibition of TLR4/MMP9 expression.

Topics: Animals; Cannabinoids; Disease Models, Animal; Down-Regulation; Hindlimb; Male; Matrix Metalloproteinase 9; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB2; Recovery of Function; Reperfusion Injury; Signal Transduction; Spinal Cord; Spinal Cord Ischemia; Sulfonamides; Toll-Like Receptor 4; Up-Regulation

Kidney ischemia reperfusion (IR) injury is an important health problem resulting in acute renal failure. After IR, the inflammatory and apoptotic process is triggered. The relation of Cannabinoid type 2 (CB2) receptor with inflammatory and apoptotic process has been determined. The CB2 receptor has been shown to be localized in glomeruli and tubules in human and rat kidney. Activation of CB2 receptor with JWH-133 has been shown to reduce apoptosis and inflammation. In this study, it was investigated whether CB2 activation with selective CB2 receptor agonist JWH-133 was protective against renal IR injury. Male Sprague-Dawley rats were divided into 5 groups (n = 45). Bilateral ischemia was treated to the IR group rat's kidneys for 45 min and then reperfusion was performed for 24 h. Three different doses of JWH-133 (0.2, 1 and 5 mg/kg) were administered to the treatment groups at the onset of ischemia. The JWH-133 application at three different doses decreased the glomerular and tubular damage. Additionally, in the renal tissue, nuclear factor-κB, tumour necrosis factor alpha, interleukin-1beta, and caspase-3 levels decreased immunohistochemically. Similarly, JWH-133 application decreased the serum tumour necrosis factor alpha, blood urea nitrogen, creatinine, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, Cystatin C, interleukin-18, interleukin-1beta, interleukin-6, and interleukin-10 levels. We found that JWH-133 and CB2 receptor activation had a curative effect against kidney IR damage. JWH-133 may be a new therapeutic agent in preventing kidney IR damage.

Topics: Acute-Phase Proteins; Animals; Blood Urea Nitrogen; Cannabinoids; Caspase 3; Creatinine; Cystatin C; Interleukin-10; Interleukin-18; Interleukin-1beta; Interleukin-6; Kidney; Lipocalin-2; Lipocalins; Male; NF-kappa B; Protective Agents; Proto-Oncogene Proteins; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB2; Reperfusion Injury; Tumor Necrosis Factor-alpha

Artery occlusion of an organ results in ischemia. When the occlusion is opened and blood flow reinstated there will be tissue injuries identified as reperfusion-induced ischemia (RII). It has been suggested that cannabinoids (CBs) may be involved in the RII. In this study, we assessed the effect of different doses of anandamide analogs and CB receptor agonists: arachidonylcyclopropylamide (ACPA, a CB1 agonist) and JWH133 (a CB2 agonist) in the RII of the mouse kidney. Three doses (0.2, 1 and 5mg/kg, i.p.) of ACPA or JWH133 were used 30min prior initiation of RII. Kidneys were removed 2 and 24h following RII and checked histologically for the grading of ischemic injury. Appropriate control groups were used as well. RII produced lesion comparable with that of ischemia. Different doses of ACPA or JWH133 prevented RII-induced lesions. It is suggestive of the CB system involvement in the kidney RII in mice.

Topics: Animals; Arachidonic Acids; Cannabinoid Receptor Agonists; Cannabinoids; Endocannabinoids; Female; Kidney; Mice; Polyunsaturated Alkamides; Reperfusion Injury