Mechanism of the Interaction of Cannabinoid System in Central Amygdale with Opioid System

Background and objectivesCannabinoids which are active compounds of marijuana show some pharmacological effects similar to the opioids. There are also functional interactions between both cannabinoid and opioid systems. In this study we investigated the role of cannabinoid receptors in central amygdala and its interaction with opioid system.MethodsIn the present study, we investigated the effects of intraperitoneal injection of opioid drugs on response-induced by intra-amygdala (intra-Amyg) microinjection of cannabinoid agents in rats, using elevated plus-maze test of anxiety. ResultsIntraperitoneal injection of morphine (3, 6 and 9 mg/kg) increased %OAT and %OAE, but not locomotor activity, showing an anxiolytic response. However, some doses of the opioid receptor antagonist, naloxone reduced %OAT and locomotor activity as well. Intra-Amyg administration of CB1 cannabinoid receptor agonist, ACPA (at the dose of 1.25 and 5 ng/rat) increased %OAT and %OAE but not locomotor activity, thus showing an anxiolytic response, which was increased by morphine (6 mg/kg, i.p.) without any interaction. Naloxone also reduced ACPA effects. Intra-Amyg administration of CB1 cannabinoid receptor antagonist, AM251 (2.5, 25 and 100 ng/rat) did not alter %OAT and %OAE but higher doses of drug (25 and 100 ng/rat) reduced locomotor activity. However, the drug in combination of morphine anxiolytic response and with naloxone decreased anxiety.ConclusionThe results may indicate an anxiolytic for CB1 cannabinoid. Our results also showed that opioid system may have interaction with cannabinoid receptor in the amygdale. Keywords: Cannabinoids, Morphine; Naloxone, Anxiety, Elevated Plus-Maz

Pretreatment with melatonin protects against cyclophosphamide-induced oxidative stress and renal damage in mice

Cyclophosphamide (CP) is widely used in treatment of different cancers. Nephrotoxicity is one of the dose-limiting side effects of CP. This study was carried out to investigate the effect of melatonin (MEL) on CP-induced nephrotoxicity in mice. In this study, 50 Swiss albino mice (20�25 g) were randomly divided into five groups. Mice were pretreated with MEL intraperitoneally (i.p) in doses of 5, 10 and 20 mg/kg for five consecutive days, and CP (200 mg/kg, i.p) was administrated on the 5th day 1 h after the last dose of MEL. Then on day 6, blood samples were collected to determine serum creatinine (Cr) and blood urea nitrogen (BUN) levels. The kidneys were used for histological examination, biochemical assays and real-time PCR studies. Malondialdehyde (MDA), glutathione (GSH), protein carbonyl (PC), nitric oxide (NO) level, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and myeloperoxidase (MPO) activity were assessed in renal tissue. In addition, the expression of SOD2 and PGx1 was measured using real-time PCR method in renal tissue. Results showed that CP administration significantly increases Cr, BUN, MDA, PC, NO level and MPO activity. It also decreases renal GSH level, SOD, GPx and CAT activity. Pretreatment with MEL (especially 20 mg/kg, i.p.) for 5 days prevented these changes; however, it did not affect the SOD activity. Our results revealed that MEL might be useful for prevention of the nephrotoxicity induced by CP through ameliorative effects on biochemical indices and oxidative stress parameters. © 2017 Société Française de Pharmacologie et de Thérapeutiqu

Effect of gemfibrozil on cardiotoxicity induced by doxorubicin in male experimental rats

Cardiotoxicity is an adverse effect of the anticancer drug doxorubicin (DOX). Gemfibrozil (GEM) is a lipid-lowering drug with a number of biological properties such as anti-inflammatory and antioxidant activities. Therefore, we decided to investigate the effect of GEM on DOX-induced cardiotoxicity in rats. Twenty-eight adult male Wistar rats were divided into four experimental groups as follows: Group I received normal saline (2 ml/kg) orally for 14 days, group II received DOX (2.5 mg/kg; in six injections; accumulative dose: 15 mg/kg) intraperitonially for 14 days, group III received DOX + GEM (100 mg/kg) orally for 14 days concomitantly with DOX administration, and group IV received GEM orally for 14 days. Lipid panel, various biochemical biomarkers, and histological observations were evaluated in serum and heart samples. According to our results, DOX significantly increased the levels of lipid panel (triglycerides, total cholesterol, and low-density lipoproteins cholesterol) as well as markers of cardiac dysfunction (Aspartate aminotransferase, Creatine kinase-muscle/brain, Lactate dehydrogenase and Cardiac Troponin I). Moreover, DOX significantly increased malondialdehyde and nitric oxide levels in cardiac tissue. Furthermore, administration of DOX reduced the level of glutathione as well as the superoxide dismutase, catalase, and Glutathione peroxidase activities. DOX-treated rats showed significantly higher tumor necrosis factor-α and interleukin-1β. GEM administration significantly attenuated the lipid panel and biochemical biomarkers in DOX-treated rats. Our results were confirmed by histopathological evaluations of the heart. Based on our findings, GEM is a promising cardioprotective agent in patients treated with DOX through mitigative effects on biochemical markers and oxidative stress indices. © 2018 Elsevier Masson SA

Gemfibrozil attenuates doxorubicin induced toxicity in renal tissues of male rats by reducing the oxidative insult and inflammation

Nephrotoxicity is a significant side effect of doxorubicin (DXN) treatment. We investigated the protective effect of gemfibrozil (GEM) co-administration with DXN on DXN induced nephrotoxicity. We divided 28 male Wistar rats into four groups of seven. Group 1 received normal saline for 2 weeks. Group 2 received 15 mg/kg DXN for 2 weeks. Group 3 received DXN + GEM for 2 weeks. Group 4 received GEM for 2 weeks. On day 15 of the experiment, blood samples were collected, animals were sacrificed and kidneys were excised for biochemical and histological evaluation. We measured serum creatinine, blood urine nitrogen, renal malondialdehyde, nitric oxide, glutathione, superoxide dismutase, glutathione peroxidase, catalase, tumor necrosis factor-α and interleukin-1β. GEM administration mitigated DXN induced nephrotoxicity. GEM co-administered with DXN attenuated the inflammatory and oxidative responses associated with DXN induced nephrotoxicity. © 2020 The Biological Stain Commission

Efficacy of 99mTc-Ciprofloxacin and 67Ga-Citrate scintigraphy to discriminate infection foci induced by staphylococcus aureus from sterile inflammation induced by carrageenan in rat

Introduction: This study was launched to evaluate the sensitivity and specificity of 99mTc-Ciprofloxacin to distinguish infection foci induced by staphylococcus aureus and inflammation lesions induced by carrageenan in the rat foot in comparison with 67Ga-Citrate scintigraphy. Methods: The labeling and quality control of 99mTc-Ciprofloxacin kits have been performed according to the manufacturer's instructions. A total number of 40 adult, male NMRI rats were randomly divided into two equal groups, one group for 99mTc- Ciprofloxacin and the other group for 67Ga-Citrate scintigraphy. Every group was subdivided into two groups equally. Septic lesion was induced by Staphylococcus aureus. Aseptic inflammation lesion was induced by carrageenan in the rat foot in the other group. The 99mTc-Ciprofloxacin and 67Ga-Citrate scintigraphy studies have been performed to evaluate the efficacy of radiotracers. Results: The images showed 67Ga uptake at the infection and inflammation sites. The infection foci could be visualized by 99mTc-Ciprofloxacin scintigraphy due to selective binding of ciprofloxacin to DNA gyrase of bacteria. The inflammation sites have been observed by non-specific uptake of 99mTc-Ciprofloxacin. None of both imaging studies have shown preferentially diagnosis of septic and aseptic inflammation lesions. The sensitivity, specificity and positive predictive value of both scintigraphic techniques were 100, 50 and 50, respectively. Conclusion: The 99mTc-Ciprofloxacin scintigraphy is sensitive for visualization of the lesion, but it could to discriminate between septic and aseptic inflammation lesions. Other modalities must be considered for interpretation of images obtained by 99mTc-Ciprofloxacin scintigraphy