Effect of Testosterone Enanthate Modeling of Polycystic Ovary on Liver Irs-2 mRNA Expression in Rats: A Brief Report

هناك العديد من النماذج الحيوانية لتكيس المبايض (PCO). يعد استخدام إينونثات التستوستيرون الخارجي إحدى طرق تحريض هذه النماذج. ومع ذلك ، يجب أيضًا دراسة تحريض مقاومة الأنسولين في تقنيات النماذج. لذلك ، تهدف الدراسة الحالية إلى التحقق من تعبير ركيزة مستقبلات الأنسولين (Irs) -2 mRNA في أنسجة الكبد لنموذج PCO الفئران. تم تقسيم تسعة عشر من قئران ويستار إلى ثلاث مجموعات. (1) تلقت مجموعة نمذجة PCO (N = 7) يوميًا 1.0 مجم / 100 جرام من إينونثات التستوستيرون المذاب في زيت الزيتون جنبًا إلى جنب مع الوصول الحر الى ماء الدكستروز ذي  التركيز 5 ٪ ، (2) مجموعة المركبات (N = 6) ، والتي تم التعامل معها مثل مجموعة PCO ، لكنهم لم يتلقوا إينونثات التستوستيرون، (3) مجموعة التحكم (N = 6) مع الرعاية المنتظمة. تم حقن جميع الحيوانات داخل الصفاق لمدة 14 يومًا. تمت دراسة التعبير عن Irs-2 mRNA باستخدام PCR في الوقت الفعلي وتم الإبلاغ عن تغييرات الطي (FC). تم اعتبار متوسط التعبير في المجموعة الضابطة بمثابة المعيار. تم العثور على حوالي 13.4 ٪ تقليل التعبير في مجموعة PCO (FC = 0.874 ، قيمة P = 0.043). لم يتم العثور على انخفاض كبير في مجموعة المركبات (FC = 0.951 ، قيمة P = 0.076). ومع ذلك ، لم يُظهر تحليل التباين فرقًا معنويًا بين جميع مجموعات الدراسة (قيمة P = 0.085). قد يؤدي النموذج الحالي لـ PCO إلى مقاومة الأنسولين على مستوى الكبد بحجم تأثير منخفض عن طريق تقليل تعبير mRNA عن Irs-2. يُقترح دراسة الجينات والجزيئات المعنية في الأنسجة الأخرى لنماذج حيوانية PCO.There are many animal models for polycystic ovary (PCO); using exogenous testosterone enanthate is one of the methods of induction of these models. However, induction of insulin resistance should also be studied in the modeling technics. Therefore, the present study aims to investigate the expression of insulin receptor substrate (Irs)-2 mRNA in the liver tissue of rat PCO model. Nineteen Wistar rats were divided into three groups; (1) PCO modeling group (N =7) received daily 1.0 mg/100g testosterone enanthate solved in olive oil along with free access dextrose water 5%, (2) vehicle group (N =6), which handled like the PCO group, but did not receive testosterone enanthate, (3) control group (N =6) with standard care. All the animals were administered via intra-peritoneal injection for 14 days. Expression of Irs-2 mRNA was studied with real-time PCR and fold changes (FC) were reported. The average of expression in the control group was considered as the calibrator. About 13.4% expression reduction was found in the PCO group (FC =0.874, P-value =0.043). No significant reduction was found in the vehicle group (FC =0.951, P-value =0.076). However, analysis of variance did not show a significant difference between all the groups of study (P-value =0.085). The present model of PCO might induce insulin resistance at liver level with a low effect size via reduction in the mRNA expression of Irs-2. Study of the involved genes and molecules in other tissues of PCO animal models is suggested

Minocycline through attenuation of oxidative stress and inflammatory response reduces the neuropathic pain in a rat model of chronic constriction injury

Objectives: Several lines of evidence showed that minocycline possesses antioxidant and anti-inflammatory properties. This study aimed to demonstrate the effects of minocycline in rats subjected to chronic constriction injury (CCI). Materials and Methods: In this study four groups (n = 6-8) of rats were used as follows: Sham, CCI, CCI + minocycline (MIN) 10 mg/Kg (IP) and CCI + MIN 30 mg/Kg (IP). On days 3, 7, 14, and 21 post-surgery hot-plate, acetone, and von Frey tests were carried out. Finally, Motor Nerve Conduction Velocity Evaluation (MNCV) assessment was performed and spinal cords were harvested in order to measure tissue concentrations of TNF_α, IL-1β, Glutathione peroxidase (GPx), Superoxide dismutase (SOD) and Malondialdehyde (MDA). Extent of perineural inflammation and damage around the sciatic nerve was histopathologically evaluated. Results: Our results demonstrated that CCI significantly caused hyperalgesia and allodynia twenty-one days after CCI. MIN attenuated heat hyperalgesia, cold and mechanical allodynia and MNCV in animals. MIN also decreased the levels of TNF_α and IL-1β. Antioxidative enzymes (SOD, MDA, and GPx) were restored following MIN treatment. Our findings showed that MIN decreased perineural inflammation around the sciatic nerve. According to the results, the neuropathic pain reduced in the CCI hyperalgesia model using 30 mg/kg of minocycline. Conclusion: It is suggested that antinociceptive effects of minocycline might be mediated through the inhibition of inflammatory response and attenuation of oxidative stress

The effect of different types of mulch and different cultivation methods on the quantitative and qualitative traits of sunflower (Helianthus annuus L.) in Ahvaz climate

To investigate the effect of mulch and different cultivation methods on the quantitative and qualitative yield of oil sunflower (Helianthus annuus L.) in Ahvaz climate, a factorial experiment in randomized complete blocks with three replications in the 2017-2018 crop year was in the research farm of Agricultural Sciences and Natural ResourcesUniversity of Khuzestan. The first factor includes different types of mulch in five levels (non-application, wheat straw, white plastic, live mulch (mung bean cultivation), and black plastic) and the second factor includes three-level cultivation method (on a flat surface, ridge cultivation, and inside the furrow cultivation). The results showed that in the flat surface and on the ridge, black plastic produced the highest amount of chlorophyll a, b, and In the inside the furrow, the highest chlorophyll a was obtained in the application of living mulch. The highest grain yield and oil yield were obtained from the interaction of wheat straw mulch × in the furrow and wheat straw mulch on the ridge. In addition, the highest harvest index was obtained in the treatment of white plastic mulch on a flat surface with an average of 51.85%. In general, it can be said that the treatment of wheat straw and straw × in the inside the furrow and wheat straw × on the ridge were superior in terms of quantitative and qualitative performance

Metformin and its anti-inflammatory and anti-oxidative effects; new concepts

Metformin is one of the oldest and commonly used blood sugar lowering drugs, having limited side effects and used as the first line treatment in patients suffering from diabetes mellitus. Moreover, various studies have emphasized on the anti-inflammatory and antioxidant role of metformin, with multiple mechanisms, which activation of AMPK by metformin has had a key role in many of them. During the searches on the internet websites of PubMed, Elsevier, Google Scholar, and Science Direct, 76 papers related to the anti-inflammatory and antioxidant role of metformin were selected and reviewed since 2003 to 2017. At the cellular level, metformin suppresses the inflammation in many cases and reduces or eliminates inflammatory factors mainly through dependent mechanisms and sometimes independent of AMPK at the cellular level and through other ways at the systematic levels. It is also effective in reducing the level of oxidative stress factors by regulating the antioxidant system of the cell. All evidence suggests the antioxidant and anti-inflammatory role of metformin in various conditions. Metformin can be an appropriate treatment option for many diseases, which inflammatory processes and oxidative stress play a role in their pathogenesis

Metformin and its anti-inflammatory and anti-oxidative effects; new concepts

Metformin is one of the oldest and commonly used blood sugar lowering drugs, having limited side effects and used as the first line treatment in patients suffering from diabetes mellitus. Moreover, various studies have emphasized on the anti-inflammatory and antioxidant role of metformin, with multiple mechanisms, which activation of AMPK by metformin has had a key role in many of them. During the searches on the internet websites of PubMed, Elsevier, Google Scholar, and Science Direct, 76 papers related to the anti-inflammatory and antioxidant role of metformin were selected and reviewed since 2003 to 2017. At the cellular level, metformin suppresses the inflammation in many cases and reduces or eliminates inflammatory factors mainly through dependent mechanisms and sometimes independent of AMPK at the cellular level and through other ways at the systematic levels. It is also effective in reducing the level of oxidative stress factors by regulating the antioxidant system of the cell. All evidence suggests the antioxidant and anti-inflammatory role of metformin in various conditions. Metformin can be an appropriate treatment option for many diseases, which inflammatory processes and oxidative stress play a role in their pathogenesis. Keywords Author Keywords:Metformin; Oxidative stress; Inflammation; AMPK KeyWords Plus:ACTIVATED PROTEIN-KINASE; C-REACTIVE PROTEIN; INDUCED PULMONARY-FIBROSIS; INDUCED OXIDATIVE STRESS; FACTOR-KAPPA-B; T-HELPER 17; INFLAMMATORY RESPONSES; FIBROBLAST MIGRATION; ALZHEIMERS-DISEASE; INSULIN-RESISTANC

Anti-inflammatory effect of AMPK signaling pathway in rat model of diabetic neuropathy

Abstract Diabetic neuropathy (DN) is characterized as Hyperglycemia activates thdisturbed nerve conduction and progressive chronic pain. Inflammatory mediators, particularly cytokines, have a determinant role in the pathogenesis of neuropathic pain. The activity of adenosine monophosphate protein kinase (AMPK), an energy charge sensor with neuroprotective properties, is decreased in diabetes. It has been reported that activation of AMPK reduces the systemic inflammation through inhibition of cytokines. In this study, we aimed to investigate the probable protective effects of AMPK on DN in a rat of diabetes. DN was induced by injection of streptozotocin (65 mg/kg, i.p.). Motor nerve conduction velocities (MNCV) of the sciatic nerve, as an electrophysiological marker for peripheral nerve damage, were measured. Plasma levels of IL-6, TNF-a, CRP were assessed as relevant markers for inflammatory response. Also, the expression of phosphorylated AMPK (p-AMPK) and nonphosphorylated (non-p-AMPK) was evaluated by western blotting in the dorsal root ganglia. Histopathological assessment was performed to determine the extent of nerve damage in sciatic nerve. Our findings showed that activation of AMPK by metformin (300 mg/kg) significantly increased the MNCV and reduced the levels of inflammatory cytokines. In addition, we showed that administration of metformin increased the expression of p-AMPK as well as decline in the level of non p-AMPK. Our results demonstrated that co-administration of dorsomorphin with metformin reversed the beneficial effects of metformin. In conclusion, the results of this study demonstrated that the activation of AMPK signaling pathway in diabetic neuropathy might be associated with the anti-inflammatory response

Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide and N-methyl-D-aspartate receptor

Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole-induced seizures in mouse considering the possible role of the nitric oxide/N-methyl-D-aspartate (NMDA) pathway. We induced seizure using intravenous administration of pentylenetetrazole. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of subeffective doses of the nonselective nitric oxide synthase (NOS) inhibitor NG-L-arginine methyl ester (10 mg/kg) and the neuronal NOS inhibitor 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of subeffective doses of minocycline (40 mg/kg). We found that inducible NOS inhibitor aminoguanidine (100 mg/kg) had no effect on the antiseizure effect of minocycline. Moreover, L-arginine (60 mg/kg), as a NOS substrate, reduced the anticonvulsant effect of minocycline. We also demonstrated that pretreatment with the NMDAreceptor antagonists ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of subeffective doses of minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration of a neuronal NOS inhibitor like NMDA receptor antagonists augmented the effect of minocycline on the hippocampal nitrite level. In conclusion, we revealed that anticonvulsant effect of minocycline might be, at least in part, due to a decline in constitutive hippocampal nitric oxide activity as well as inhibition of NMDA receptors

Antioxidative and anti-inflammatory impact of valsartan against renal ischemia-reperfusion injury; role of nitric oxide signaling pathway

Introduction: Renal ischemia reperfusion injury is one of the main causes of acute renal failure, which is associated with high mortality. Tissue damage caused by ischemia-reperfusion occurs due to the release of oxygen free radicals. Type I angiotensin receptor antagonists such as valsartan can be useful in the treatment of chronic kidney disease and hypertension. Objectives: We aimed to evaluate the protective effect of valsartan against renal ischemia reperfusion via antioxidant property and nitric oxide (NO) signaling pathway. Materials and Methods: Fifty male Wistar rats (220 +/- 10 g) were randomly divided into five groups as follows: Group 1; healthy rats without ischemia-reperfusion (control group). Group 2; rats with ischemia reperfusion (IR) (IR control group). Group 3; rats with IR which received 30 mg/kg valsartan orally. Group 4; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-NAME. Group 5; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-arginine. To induce ischemia-reperfusion, rats were anesthetized with thiopental and underwent surgery. Then, we induced ischemia with blocking blood vessels for 45 minutes by clamping. Biochemical parameters including urea and creatinine were measured using commercial kits. Oxidative stress and inflammatory parameters were measured by ELISA method. Renal tissues were stained with hematoxylin and eosin. Finally, the Kolmogorov-Smirnov test was used to determine the normal distribution of data. Results: The findings of this study indicated that treatment with valsartan and valsartan plus L-arginine leads to significant decrease in the serum levels of creatinine, urea, and albumin/creatinine, malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in contrast to IR control group which has increased level of these parameters. On the other hand, treatment with valsartan and valsartan plus L-arginine lead to increase in the serum levels of glutathione peroxidase (GPX), in contrast to ischemia reperfusion control group. Conclusion: Our data revealed that valsartan as a type I angiotensin receptor antagonist could decrease oxidative stress and inflammation due to renal ischemia reperfusion injury. Hence, valsartan could propose as a therapeutic agent for kidney diseases such as renal ischemia-reperfusion injury regarded to these renoprotective effects. Keywords Author Keywords:Valsartan; Renal ischemia reperfusion; Antioxidant property; Kidney; Acute renal failure; Reactive oxygen species KeyWords Plus:KIDNEY-DISEASE; HYPERTENSIO

The antinociceptive effects of rosuvastatin in chronic constriction injury model of male rats

Introduction: According to studies, statins possess analgesics and anti-inflammatory properties. In the present study, we examined the antinociceptive, anti-inflammatory and antioxidative effects of rosuvastatin in an experimental model of Chronic Constriction Injury (CCI). Methods: Our study was conducted on four groups; sham, CCI (the control group), CCI+rosuvastatin (i.p. 5 mg/kg), and CCI+rosuvastatin (i.p. 10 mg/kg). We performed heat hyperalgesia, cold and mechanical allodynia tests on the 3rd, 7th, 14th, and 21st after inducing CCI. Blood samples were collected to measure the serum levels of Tumor Necrosis Factor (TNF)-α, and Interleukin (IL)-6. Rats' spinal cords were also examined to measure tissue concentration of Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) enzymes. Results: Our findings showed that CCI resulted in significant increase in heat hyperalgesia, cold and mechanical allodynia on the 7th, 14th and 21st day. Rosuvastatin use attenuated the CCI-induced hyperalgesia and allodynia. Rosuvastatin use also resulted in reduction of TNF-α, IL-6, and MDA levels. However, rosuvastatin therapy increased the concentration of SOD and GPx in the CCI+Ros (5 mg/kg) and the CCI+Ros (10 mg/kg) groups compared to the CCI group. Conclusion: Rosuvastatin attenuated the CCI-induced neuropathic pain and inflammation. Thus, antinociceptive effects of rosuvastatin might be channeled through inhibition of inflammatory biomarkers and antioxidant properties