Hossein Ali Arab

Background: Ischemia preconditioning (IPC) is known as a protective procedure against the injury induced by ischemia/reperfusion (IR) injury. There is also evidence that the administration of opioids may have the same effects on the injury. Objectives: The aim of this study was to investigate the ameliorative effects of simultaneous use of opium and IPC on lobar IR injury in the rat liver. Methods: Twenty-five adult male rats were randomly divided into five groups: 1) Sham-operated, 2) IR, 3) IR+IPC, 4) Opium+IPC+IR and 5) Naloxone+opium+IPC+IR. At the end of the reperfusion, blood and tissue samples were obtained to assay alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the blood, as well as to determine oxidative stress by measuring malondialdehyde (MDA) levels, total antioxidant capacity (TAC) values, and superoxide dismutase (SOD) and catalase (CAT) activities in the liver tissues. Results: The levels of ALT, AST and MDA were significantly increased in the IR group compared to the sham-operated group (P<0.05). However, the application of IPC and IPC+opium significantly decreased the release of these enzymes, while the simultaneous application of opium and IPC had a stronger restorative effect on the IR injury (P<0.05). The recovery effects induced by opium+IPC in terms of TAC, SOD and CAT were also higher than that of the IPC alone. However, the use of naloxone significantly inhibited the protective effects induced by the opium. Conclusion: The simultaneous use of opium and IPC is able to accelerate the protective effects of IPC on IR injury.

Purpose: Hepatic ischemia post-conditioning (IPOC) is shown to protect the liver from injury induced by ischemia/reperfusion (IR). However, the mechanism underlying this protection has remained elusive. The present study aimed to investigate the role of the interleukin 6-Janus kinase-signal transducers and activators of transcription (IL-6-JAK-STAT) pathway in the protective effect of hepatic IPOC against the IR-induced injury in the liver. Methods: 25 rats were randomly divided into 5 groups of 1) sham-operated, 2) IR, 3) IR+hepatic IPOC, 4) IR+ tofacitinib (TOFA), and 5) IR+TOFA+ hepatic IPOC. The changes induced by IR and the effects of different treatments were assessed by enzyme release, histopathological observations, the serum level of IL-6, and the occurrence of apoptosis detected via the expression of the Bax/Bcl-2 ratio. Results: The hepatic IPOC improved the liver injury induced by IR as shown by histological changes, reduction of IL-6 level, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) compared to the IR group (p<0.001, p<0.05, p<0.05, respectively). There was also downregulation of the Bax/Bcl2 ratio in the rats exposed to IR + hepatic IPOC compared with those in the IR group (p<0.05). However, TOFA, an inhibitor of JAK-STAT activity, inhibited the protective effect of hepatic IPOC. Conclusion: It suggests that the protective effect of hepatic IPOC against IR-induced injury may be mediated by activating the IL-6-JAK-STAT pathway.

The coronavirus disease 19 (COVID-19) outbreak in Wuhan, Hubei province, is a global health problem affecting about 212 countries around the world, highlighting the importance of the global recruitment of scientists to find a way for managing this burden. So far, many studies have been conducted to find a treatment for COVID-19, some of which indicated promising results. In this situation, gathering the previously published evidence may provide new hypotheses/ solutions in this regard. Based on the role of inflammation in COVID-19-related deaths, we attempted to find a rational relationship between Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling and COVID-19 and inform JAK/STAT signaling inhibitors as candidates to manage or even prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, it is hoped that the present study provides new clues about the relationship between JAK/STAT signaling and the SARS-CoV-2 infection to highlight the role of JAK/STAT inhibitors as a possible treatment for managing inflammatory situations observed in the SARS-CoV-2 infection.

The use of cyclosporine A (CsA) is associated with different adverse effects including hypertension and nephrotoxicity. The present study aimed to compare the inhibitory effects of l-arginine &l-citrulline on CsA-induced blood pressure and biochemical changes in the serum of rats. Thirty-six rats were divided into 6 groups received daily: (1) 1ml distilled water, (2) 200mg/kg l-citrulline IP, (3) 25mg/kg CsA SC, (4) CsA+l-citrulline with the same dose of the former groups, (5) 200mg/kg l-arginine IP and (6) l-arginie+CsA with the same doses of group 4 for 7 days. The changes in the blood pressure, heart rate, creatinine, BUN, glucose and C-reactive protein (CRP) of the serum were determined in the treated animals. Significant (p<0.001) increase was shown in the blood pressure and heart rate of CsA treated rats compared to the control group. There were also a significant (p<0.05) increase in the creatinine, BUN and glucose, but a decrease in the CRP value in the CsA-treated group. However, l-citrulline significantly (p<0.001) inhibited the changes in the blood pressure and heart rate in CsA-treated as well as it was able to reduce blood pressure in non-treated group significantly (p<0.01). l-citrulline also inhibited the increased levels of BUN and creatinine induced by CsA, while, l-arginine was able to prevent the increased blood pressure and creatinine occurs after administration of CsA. These findings suggest that the l-citrulline is more efficient than l-arginine against the adverse effects induced by cyclosporine.

The original version of this article unfortunately contained a mistake in the author group section. The correct name of the fourth author is “Reza Shirkoohi.”The original article has been corrected.

Some epidemiological studies have shown an association between opium consumption and the incidence of gastrointestinal (GI) cancer. The present study was designed to investigate the effects of opium on the initiation of GI cancer in rats.

This study aimed to examine the hypothesis that an antiarrhythmic effect might be obtained by ischemic preconditioning of the liver, and also to characterize the potential underlying mechanisms. Male Wistar rats were anesthetized by thiopental sodium (50 mg/kg, IP) followed by IV injection of heparin (250 IU). Remote ischemic preconditioning (RIPC) was induced by 3 cycles of 5 min liver ischemia followed by 5 min of reperfusion. The hearts were excised within 5 min after the final cycle of preconditioning and perfused using Langendorff's system. The isolated perfused hearts were subjected to 30 min global ischemia followed by 90 min reperfusion. The myocardial arrhythmias induced by ischemia- reperfusion (I/R) were determined in accordance with the guidelines of Lambeth Conventions. The potential role of KATP channels on RIPC was assessed by injection of glibenclamide (nonselective KATP blocker) or 5-hydroxydecanoate (mitochondrial KATP blocker) on rats 30 and 15 min before induction of RIPC in the liver, respectively. Hepatic remote preconditioning of the heart significantly (P<0.0001) prevented the incidence of myocardial arrhythmias induced by I/R in the perfused hearts (5.33±1.54 vs. 32.33±6.44,). However, the protective effects of remote preconditioning was significantly (P<0.01) abolished by the KATP blocker, glibenclamide (25.5±4.9 vs. 5.33±1.54,). Hepatic RIPC may prevent the arrhythmias induced by I/R in the isolated perfused hearts via KATP channels.

The enteric nervous system (ENS) arises from the enteric neural crest-derived cells (ENCCs), and many molecules and biochemical processes may be involved in its development. This study examined the effects of modulating embryonic nitric oxide (NO) activity on the intestinal motility induced by ENS. One-hundred-and-twenty fertilized chicken eggs were assigned to three main groups and incubated at 37°C and 60% humidity. The eggs were treated with N ^G -nitro-l-arginine methyl ester (l-NAME), sodium nitroprusside (SNP), l-arginine (l-Arg) or vehicle from days 3 (1st group), 7 (2nd group) and 10 (3rd group) of incubation and continued up to day 18. On day 19, the embryos were sacrificed, the jejunal and colorectal segments were taken and the intestinal motility was assessed using isolated organ system. The intestinal motility was recorded normally and following cholinergic, adrenergic and non-adrenergic non-cholinergic (NANC) stimulations. The ENS structure was assessed by immunohistochemistry (IHC) using glial fibrillary acidic protein (GFAP). Rhythmic intestinal contractions were seen in all treatment groups, but inhibition of NO in the l-NAME-treated embryos caused significant decrease (ppp<0.05) reduced in the l-NAME-treated embryos. This study showed that the inhibition of NO caused a deficient development of the ENS, leading to a decrease in the frequency and amplitude of the intestinal contractions and reduced the responsiveness to adrenergic, cholinergic and NANC signalling.