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BackgroundHemorrhagic shock followed by resuscitation is conceived as an insult frequently induces a systemic inflammatory response syndrome and oxidative stress that results in multiple-organ dysfunction syndrome including acute lung injury. MK-886 is a leukotriene biosynthesis inhibitor exerts an anti inflammatory and antioxidant activity.ObjectivesThe objective of present study was to assess the possible protective effect of MK-886 against hemorrhagic shock-induced acute lung injury via interfering with inflammatory and oxidative pathways.Materials and methodsEighteen adult Albino rats were assigned to three groups each containing six rats: group I, sham group, rats underwent all surgical instrumentation but neither hemorrhagic shock nor resuscitation was done; group II, Rats underwent hemorrhagic shock (HS) for 1 hr then resuscitated with Ringer's lactate (1 hr) (induced untreated group, HS); group III, HS + MK-886 (0.6 mg/kg i.p. injection 30 min before the induction of HS, and the same dose was repeated just before reperfusion period). At the end of experiment (2 hr after completion of resuscitation), blood samples were collected for measurement of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The trachea was then isolated and bronchoalveolar lavage fluid (BALF) was carried out for measurement of leukotriene B4 (LTB4), leukotriene C4 (LTC4) and total protein. The lungs were harvested, excised and the left lung was homogenized for measurement of malondialdehyde (MDA) and reduced glutathione (GSH) and the right lung was fixed in 10% formalin for histological examination.ResultsMK-886 treatment significantly reduced the total lung injury score compared with the HS group (P < 0.05). MK-886 also significantly decreased serum TNF-α & IL-6; lung MDA; BALF LTB4, LTC4 & total protein compared with the HS group (P < 0.05). MK-886 treatment significantly prevented the decrease in the lung GSH levels compared with the HS group (P < 0.05).ConclusionsThe results of the present study reveal that MK-886 may ameliorate lung injury in shocked rats via interfering with inflammatory and oxidative pathways implicating the role of leukotrienes in the pathogenesis of hemorrhagic shock-induced lung inflammation.

Objective:To study the effect of metformin on amelioration of hepatotoxicity induced by methotrexate.Materials and Methods:After a 2-weeks of acclimatization period, the animals were randomly separated into three groups (seven rabbits each), all groups were maintained on standard chow diet throughout the experiment (8 weeks). Group 1 was treated with normal saline water (control), Group 2 with methotrexate (MTX, hepatotoxic), and Group 3 with MTX plus metformin. Induction of hepatotoxicity was carried out by administration of MTX to the rabbit in a dose of 0.25 mg/kg /day i.m. for 8 weeks.Results:The treatment with MTX to rabbits for 8 weeks resulted in significant changes in serum liver enzymes, as compared to the baseline group. SGOT, SGPT, ALP, and bilirubin were significantly increased (P < 0.001), while total serum protein was significantly decreased. Similarly, 8 weeks of MTX treatment produced significant (P < 0.001) prolongation in PT. PTT was not significantly changed. It was found that serum MDA levels and SOD activity were significantly increased (P < 0.001), while serum GSH levels were significantly decreased (P < 0.001). Adding metformin to MTX is found to be significantly (P < 0.001) reduced the liver function test and shortening of PT and a significant increase in TSP (P < 0.001).Conclusion:It can be concluded that administration of metformin restored the altered liver function parameters and produced significant improvement in liver histopathological findings. Therefore, this additive drug possesses hepatoprotection against MTX-induced hepatotoxicity.

BackgroundErectile dysfunction is a common problem in type 2 diabetic patients who are at higher risk of cerebrovascular events, and it's recorded with sildenafil, a drug which is primarily used for erectile dysfunction.ObjectivesWe tested the hypothesis whether or not sildenafil modulates cerebrovascular reactivity (CVR) in patients with type 2 diabetes mellitus.MethodsA total of 35 male participants were enrolled; eighteen with type 2 diabetes mellitus matched with seventeen normal individuals. Transcranial Doppler Ultrasonographic examination (TCD) was performed for all participants to insonate the middle cerebral artery (MCA) through a trans-temporal window. CVR was assessed by using breath holding (BH)-hyperventilation (HV) test, before and after oral 50 mg sildenafil; recordings were analyzed by using SPSS program version 12.ResultsIn normal individuals, sildenafil did not result in statistically significant change in breath holding index (BHI) from 0.91 ± 0.11 to 0.81 ± 0.09 and full range of vasodilatation (FVD) from (59.4% ± 6.3%) to (53.7% ± 4.9%). In diabetic patients, giving sildenafil resulted in significant increase in BHI (from 0.74 ± 0.14 to 1.03 ± 0.14) and FVD (from 60.2% ± 4.96% to 74% ± 4.8%), (p < 0.05).ConclusionSildenafil significantly improves CVR in type 2 diabetic patients but not in normal subjects.

The results of the present study reveal that montelukast may ameliorate lung injury in shocked rats by interfering with inflammatory and oxidative pathways, implicating the role of leukotrienes in the pathogenesis of haemorrhagic shock-induced lung inflammation.