Hepatoprotective effects of melatonin and celecoxib against ethanol-induced hepatotoxicity in rats

Abstract

Objectives: Several studies demonstrated the antioxidant and anti-inflammatory role of melatonin and celecoxib. This study is designed to explore the underlying mechanism of hepatoprotective effects of melatonin and celecoxib against ethanol-induced hepatotoxicity by morphological, and biochemical approaches.

Materials and methods: Adult male rats were divided into five groups: saline, ethanol, melatonin, and celecoxib were administered for 11 consecutive days after ethanol injection. Biochemical analyses were performed for the determination of glutathione (GSH), glutathione S-transferase (GST), and inducible nitric oxide (iNOS). Immunohistochemistry was performed to determine the level of different inflammatory markers.

Results: Histopathological results showed that ethanol-induced marked hepatic injury leads to cloudy swelling, hydropic degeneration, apoptosis, and focal necrosis in all hepatic zones. Biochemical analysis revealed significant increases in serum transaminases and alkaline phosphatase in the ethanol group. Oxidative stress associated with attenuated antioxidant enzymes was also spotted in the ethanol group, as ethanol down-regulated GSH, GST, and upregulated NO. Additionally, ethanol increased the activation and the expression of tumor necrotic factor (TNF-α), p-NF_KB, and COX2. Finally, hepatic cellular apoptosis was clearly obvious in ethanol intoxicated animals using activated JNK staining.

Conclusion: These results provided pieces of evidence that the hepatoprotective effect of melatonin and celecoxib is possibly mediated through the modulation of JNK and TNF-α signaling pathways with subsequent suppression of inflammatory and apoptotic processes.     

Preparation of cellulosic Ag-nanocomposites using an ionic liquid

Cellulose-based nanocomposites have gained much attention due to their remarkable biological properties such as biodegradability, biocompatibility, and low toxicity. In this research work, 1-h-3-methylimidazolium hydrogen sulfate ionic liquid was employed as an efficient solvent for preparation of cellulosic Ag-nanocomposites (CRC/AgNPs composite) from Neem plant. Ionic liquid plays a dual role in obtaining cellulose-rich compound (CRC; removing lignin and hemicellulose components) and plant’s extract (phenolic compounds such as flavonoids, tannins, etc.) that reduces the AgNO₃ into AgNPs for preparation of CRC/AgNPs composite. The prepared CRC/AgNPs composite was characterized using XRD, FTIR and SEM techniques. The XRD and FTIR spectral analysis showed the characteristic peaks assigned to cellulosic constituent and AgNPs. SEM analysis revealed the particles in the range from 26 to 56 nm. The CRC/AgNPs composite was evaluated for its antibacterial and mechanical properties. The antibacterial activity against S. aureus and E. coli for CRC/AgNPs composite was observed in comparison to CRC. Cell viability and morphology were performed on MC3T3-E1 cells which showed no as such toxicity for the prepared CRC/AgNPs composite. Moreover, the addition of CRC/AgNPs composite as a filler increased the compression strength of polymeric materials.     

New application of the autotrans: autologous support of the organ donor and salvage of the donor's red blood cells for the transfusion support of organ recipients

Organ donation is usually limited to solid tissues; paradoxically, organ donors undergoing explant are often transfused in preparation for or during surgery. This practice increases the requirement for blood and adds immunological and infectious risks for both recipients and donors of grafts. We have investigated the possibility of supporting an explant with intraoperative blood salvage and, in the case of a cadaver donor, at the end of the operation, salvaging blood for potential use in the graft recipient. This preliminary report describes the technique and the results obtained in two procedures. The volume of red cells with a hematocrit of 55% obtained from the two donors was 2,090 and 1,180 ml, respectively. These components were employed for the transfusion support of the organ recipients.     

Profile of thoracic trauma–An analysis of 350 cases

The incidence of chest trauma is rising rapidly and opinion continues to differ on its management. Our experience with 350 consecutive patients of chest injuries between January, 1983 and June, 1986 was reviewed. There were 300 males and 50 females. The average age was 29 years. Two-hundred and seventy-five (80%) were under forty years of age. The commonest presenting features were pain (100%), and dyspnoea (58.57%). Features of peripheral circulatory failure were found in 20 per cent. Ninety (25.71%) had other associated injuries. Three hundred (85.71%) were treated conservatively with 20 (6.66%) deaths. Forty-eight (13.7%) patients underwent surgical exploration (thoracotomy in 34 and laparotomy in 14 patients) with 8 deaths. Remaining 2 patients died in the casualty soon after arrival. The overall mortality was 8.57 per cent. The average period of hospitalisation was 9.5 days.     

Cholesterol reduction using manufactured foods high in monounsaturated fatty acids: a randomized crossover study

In two separate studies, the cholesterol-lowering efficacy of a diet high in monounsaturated fatty acids (MUFA) was evaluated by means of a randomized crossover trial. In both studies subjects were randomized to receive either a high-MUFA diet or the control diet first, which they followed for a period of 8 weeks; following a washout period of 4-6 weeks they were transferred onto the opposing diet for a further period of 8 weeks. In one study subjects were healthy middle-aged men (n 30), and in the other they were young men (n 23) with a family history of CHD recruited from two centres (Guildford and Dublin). The two studies were conducted over the same time period using identical foods and study designs. Subjects consumed 38% energy as fat, with 18% energy as MUFA and 10% as saturated fatty acids (MUFA diet), or 13% energy as MUFA and 16% as saturated fatty acids (control diet). The polyunsaturated fatty acid content of each diet was 7%. The diets were achieved by providing subjects with manufactured foods such as spreads, 'ready meals', biscuits, puddings and breads, which, apart from their fatty acid compositions, were identical for both diets. Subjects were blind to which of the diets they were following on both arms of the study. Weight changes on the diets were less than 1 kg. In the groups combined (n 53) mean total and LDL-cholesterol levels were significantly lower at the end of the MUFA diet than the control diet by 0.29 (SD 0.61) mmol/l (P < 0.001) and 0.38 (SD 0.64) mmol/l (P < 0.0001) respectively. In middle-aged men these differences were due to a mean reduction in LDL-cholesterol of -11 (SD 12)% on the MUFA diet with no change on the control diet (-1.1 (SD 10)%). In young men the differences were due to an increase in LDL-cholesterol concentration on the control diet of +6.2 (SD 13)% and a decrease on the MUFA diet of -7.8 (SD 20)%. Differences in the responses of middle-aged and young men to the two diets did not appear to be due to differences in their habitual baseline diets which were generally similar, but appeared to reflect the lower baseline cholesterol concentrations in the younger men. There was a moderately strong and statistically significant inverse correlation between the change in LDL-cholesterol concentration on each diet and the baseline fasting LDL-cholesterol concentration (r -0.49; P < 0.0005). In conclusion, diets in which saturated fat is partially replaced by MUFA can achieve significant reductions in total and LDL-cholesterol concentrations, even when total fat and energy intakes are maintained. The dietary approach used to alter fatty acid intakes would be appropriate for achieving reductions in saturated fat intakes in whole populations.