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19 results on '"Koti, Rahul S"'

17. Effect of ischaemic preconditioning on hepatic oxygenation, microcirculation and function in a rat model of moderate hepatic steatosis

Author

KOTI, Rahul S., YANG, Wenxuan, GLANTZOUNIS, Georgios, QUAGLIA, Alberto, DAVIDSON, Brian R., and SEIFALIAN, Alexander M.

Abstract

IPC (ischaemic preconditioning) may protect the steatotic liver, which is particularly susceptible to I/R (ischaemia/reperfusion) injury. Hepatic steatosis was induced in Sprague–Dawley rats with a high-cholesterol (2%) diet for 12 weeks after which rats were subjected to I/R (ischaemia/reperfusion; 45 min of lobar ischaemia followed by 2 h of reperfusion). Rats were divided into three study groups (n=6 each) receiving: (i) sham laparotomy alone, (ii) I/R, and (iii) IPC (5 min of ischaemia, followed by 10 min of reperfusion) before I/R. Hepatic extra- and intra-cellular oxygenation and HM (hepatic microcirculation) were measured with near-infrared spectroscopy and laser Doppler flowmetry respectively. Plasma liver enzymes and hepatic tissue ATP were measured as markers of liver injury. Histology showed moderate-grade steatosis in the livers. At the end of 2 h of reperfusion, I/R significantly decreased extra- and intra-cellular oxygenation concomitant with a failure of recovery of HM (21.1±14.4% of baseline; P<0.001 compared with sham animals). IPC increased intracellular oxygenation (redox state of the copper centre of cytochrome oxidase; P<0.05 compared with rats receiving I/R alone) and flow in HM (70.9±17.1% of baseline; P<0.001 compared with rats receiving I/R alone). Hepatocellular injury was significantly reduced with IPC compared with I/R injury alone (alanine aminotransferase, 474.8±122.3 compared with 5436.3±984.7 units/l respectively; P<0.01; aspartate aminotransferase, 630.8±76.9 compared with 3166.3±379.6 units/l respectively; P<0.01]. In conclusion, IPC has a hepatoprotective effect against I/R injury in livers with moderate steatosis. These data may have important clinical implications in liver surgery and transplantation.

Published
2005
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18. Contributors

Author

Akiyama, The late Hiroshi, Appleton, Shaun G., Baker, Daryll M., Brueton, Richard N., Butler, Peter E.M., Cheung, Hester Y.S., Cresswell, Adrian B., Damrah, Osama, Davey, Clare, Davidson, Brian R., Davis, Meryl, Dawas, Khaled I., D'Souza, Rovan E., England, James A., Ghosh, Debashis B., Goddard, Nicholas, Hall, Nigel J., Keshtgar, Mo, Kiely, Edward, Kim, Dae S., Kirk, R.M., Koti, Rahul S., Kurzawinski, Tom R., Leicester, Roger J., Li, Michael K.W., Lim, Eric K.S., Magos, Adam, Mahendran, Arundathi O., Mallett, Sue, Maruthainar, Nimalan, Mason, Robert C., McDermott, Peter, Miltsios, Konstantinos G., Mosahebi, Afshin, Novell, Richard, Ogunbiyi, Olagunju A., Pridgeon, Simon, Prout, Jeremy, Rahman, Sakhawat H., Rolles, Keith, Roy, Debabrata, Sadri, Amir, Smith, Gillian, Smith, Joel A., Stearns, Michael P., Sujendran, Vijay, Tai, Nigel R.M., Thomas, Benjamin R., Thorne, Lewis W., Udagawa, Harushi, Uff, Christopher E.G., Vaizey, Carolynne Jane, Veitch, Peter, Ward, Nicholas J., Warusavitarne, Janindra, Watkinson, John C., Whitelaw, Douglas E., and Winslet, Marc C.

Published
2013
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19. The role of thiols in liver ischemia-reperfusion injury.

Author

Glantzounis GK, Yang W, Koti RS, Mikhailidis DP, Seifalian AM, and Davidson BR

Subjects
Animals, Humans, Liver drug effects, Liver metabolism, Liver Diseases metabolism, Reperfusion Injury metabolism, Sulfhydryl Compounds therapeutic use, Liver blood supply, Liver Diseases drug therapy, Reperfusion Injury drug therapy, Sulfhydryl Compounds physiology
Abstract

Thiol-containing compounds have an essential role in many biochemical reactions due to their ability to be easily oxidised and then quickly regenerated. Main representatives are glutathione, lipoic acid and thioredoxin which are synthesised de novo in mammalian cells. N-acetylcysteine and Bucillamine are synthetic thiols which have been administered in experimental and clinical studies for treatment of conditions associated with oxidative stress. Ischemia and reperfusion (I/R) injury is characterised by significant oxidative stress, characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. I/R occurs in a variety of clinical settings such as liver resection, organ transplantation, haemorrhagic shock with fluid resuscitation, heart surgery, myocardial infarction followed by reperfusion and laparoscopic surgery. In these circumstances, the administration of antioxidant agents such as thiols, could provide protection from the harmful effects of I/R injury. However, the ability of thiol compounds to reduce free radicals is associated with the formation of thiyl radicals and the rate and efficiency of removal of thiyl radicals has a critical effect on antioxidant or prooxidant actions of thiols in the cells. The aim of this review is to present the mechanisms by which thiols act as antioxidants and signalling molecules and the experimental and clinical evidence regarding their role in I/R injury with a particular emphasis on liver I/R. The current evidence suggests that thiols ameliorate I/R injury and that their clinical significance should be further evaluated in large scale randomised clinical trials.

Published
2006
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