Sameer Hassan Abboud Al-Rekabi

Abstract: Background: Acute pancreatitis (AP) is severe inflammation of the pancreas that can be of two major types: mild AP and severe AP. In this case, some pancreatic cells can produce various pro-inflammatory cytokines and transcription factors thereby affecting the function of pancreas. Objective: to study the efficacy of Ibudilast in comparison with octreotide, in a rat model of AP. Methods: A total of 48 male rats were randomly divided into 8 groups (6 per each). AP was induced by Larginine model which has a high reproducibility. Octreotide and Ibudilast were administered individually or in combination at 0, 8or 16 hr after induction. After 24 hr of treatment, each rat was weighed and blood samples were collected for measurement of biochemical markers, and then the pancreas was extracted to obtain the pancreatic weight to the total body weight (PW/TBW) ratio and for vertical gel electrophoresis experiments. Results: In both octreotide-treated group and ibudilast-treated group, there were statistically significant decrease in serum pro-calcitonin (PCT) and tumor necrosis factor-alpha (TNF-α) when compared to control group or sham group, as well as, a decrease in PW/TBW ratio and in nuclear factor kappa B (NF- ?B)protein level using vertical gel electrophoresis. However, in octreotide + ibudilast-treated group there was no statistically significant difference when compared with groups treated with either agents. Conclusion: Ibudilast and octreotide can significantly attenuate the local and systemic effect of AP. The efficacy of ibudilast and octreotide are almost the same. Co-treatment of rats with both Ibudilast and octreotide has no preferential effect when compared with rats treated with the individual agent.

Background Doxorubicin (DOX) is commonly used in the treatment of many types of cancers but its cardiotoxicity is limiting its clinical use. Beyond its anticoagulant action, enoxaparin (ENX), a low molecular weight heparin, has been shown to exert multiple pharmacological actions including antioxidant, anti-inflammatory and antiapoptotic effects. Therefore, the current study aimed to assess if ENX could ameliorate cardiotoxicity induced by DOX. Methods Twenty-one adult male Wistar albino rats were randomly allocated into three groups (n = 7 each) of control, receiving 0.9% saline (i.p.), DOX, receiving 2.5 mg/kg of DOX (i.p.) thrice weekly; and DOX + ENX, receiving ENX (250 IU/kg/day i.p.) and a DOX dose equivalent to that of the DOX only group. Results DOX-induced cardiotoxicity was indicated by marked increases in cardiac troponin I (cTnI) and severe histological lesions, which significantly correlated with cardiotoxicity, oxidative stress, inflammation and apoptosis markers, compared to controls. DOX group also showed elevations in malondialdehyde (MDA), a marker of oxidative stress, and reductions in total antioxidant capacity (TAC). Cardiac inflammatory markers including tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) and caspase-3, an apoptotic marker, were also elevated in the DOX group. DOX, however, did not significantly alter brain natriuretic peptide (BNP) levels. ENX significantly attenuated, but not completely reversed, DOX-induced cardiotoxicity through lowering cTnI and improving cardiomyopathy histopathological scores as compared to the DOX group. ENX also decreased MDA, increased TAC of rats’ heart to levels relatively comparable to control. Significant reductions in TNF-α, IL-1β and caspase-3 were also observed following ENX treatment relative to the DOX only group. Conclusions Collectively, these results describe a cardioprotective effect for ENX against DOX-induced cardiotoxicity which is likely facilitated via suppression of oxidative stress, inflammation and apoptosis. Keywords: Doxorubicin, Cardiotoxicity, Low molecular weight heparin, Antioxidant, Inflammatory markers and caspase-3

ABSTRACT: Acute pancreatitis (AP) is a common emergency presentation and can be disabling. There is significant morbidity and mortality associated with AP, and it places a considerable burden on the healthcare system. Octreotide and N-acetylcysteine have been shown to have a protective effect in induced severe acute pancreatitis in rats. This study aim to clarify the protective potential effect of these two medications on the prognostic and inflammatory parameters in severe acute pancreatitis in rats. 40 adult male rats were allocated to five groups (n=8), control group, AP group, octreotide group, NAC group, combination group. Rats with severe acute pancreatitis have significant (p>0.05) higher levels of lipase, PMN elastase, urea, IL-1ß and significant (p>0.05) lower levels of TAC as compared with control group. Rats treated by octreotide and NAC have significant lower levels of lipase, PMN elastase, urea, IL-1ß and significant (p>0.05) higher levels of TAC as compared with AP group. Furthermore octreotide has antioxidant and anti-inflammatory activity better than NAC. Prognostic markers are possible predictors of outcome, we found that PMN elastase is a good early predictor and start to peak in the first hours of the disease faster than urea, they are positively correlated with the severity of the disease also the protective effects of Octreotide treated group were more than those carried out in NAC treated group.

Abstract Objective Acute pancreatitis continues to be associated with significant rates of mortality and morbidity, and therapeutic options are stillvery limited. Various theories have been suggested regarding the pathophysiology of acute pancreatitis, lot of research into differentmedical treatments for the treatment of acute pancreatitis, but it is not clear what benefits each treatment has, or indeed if any medicaltreatment is beneficial apart from supportive treatment.Aim To clarify the potential therapeutic effect of octreotide, trimetazidine, and their combination in acute pancreatitis.Methods Acute pancreatitis was induced by L-arginine and treated with octreotide subcutaneously, trimetazidine intraperitoneally andcombination therapy by octreotide and trimetazidine. The rats were followed for 24 h. At the 24th hour we determined serum levels oftumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), total antioxidant capacity (TAC), lipase, and amylase, and the pancreatic tissues wereanalyzed histopathologically.Results TNF-α (P < 0.001), IL-1β (P < 0.001), TAC (P < 0.001), lipase (P < 0.001), and amylase (P < 0.001) serum levels and scores ofhistopathological changes (P < 0.05) were significantly lower in combination group as compared with both octreotide and trimetazidinegroups.Conclusion Combination treatment markedly decreases biochemical and histopathological changes in acute pancreatitis, thus amelioratepancreatic injury in l-arginine induced acute pancreatitis.