L-Carnitine in Intestinal Ischemia/Reperfusion Injury J Clin Med Res • 2011;3(2):78-84 Table 4. The Levels of TNF-α and Interleukins in Arterial Serum (pg/ml) Groups S IR IR+L n 10 10 10 TNF-α 53.82 ± 8.94Δ 575.02 ± 50.56* 104.86 ± 10.61 Δ P < 0.05 compared to IR and IR+L groups * P < 0.05 compared to IR+L group IR, apoptosis is the major mode of cell death in the destruc- tion of epithelial cells [23]. The intestinal IR injury can lead to mucosal cells en- ergy exhaustion and is also associated with decrease in ATP synthesis [24-26]. Mitochondrium is one of the most impor- tant organelle and regarded as a “dynamic factory”, and it is vulnerable to injury due to IR. Undoubtedly, the damage of mitochondria will induce energy exhaustion and failure of maintenance of cellular basic functions. The defective mi- tochondrial oxidative phosphorylation and metabolic com- promise play an important role in IR injury [27]. Increased ROS changes the mitochondrial membrane permeability and results in opening of mitochondrial permeability transition (MPT) [28]. The opening of MPT is a key event in cell death after ischemia-reperfusion [12, 13, 29]. Opening of the non- speciﬁc mitochondrial permeability transition pore (mPTP) in the inner mitochondrial membrane results in the collapse of the membrane potential (Δψm), uncoupling of the respira- tory chain, and efﬂux of cytochrome c and other proapop- totic factors that may lead to either apoptosis or necrosis [30]. Opening of the mPTP is triggered by Ca2+ overload and excessive production of ROS in the early minutes of reﬂow, which is crucial event in reperfusion injury [31, 32]. Grifﬁths and Halestrap’s study [33] have demonstrated that in isolated rat heart, the mPTP remained closure throughout ischemia but opened at the time of reperfusion. L-Carnitine can carry long-chain fatty acylgroups into mitochondria for beta-oxidation. And it acts as a scavenger of oxygen free radical, relief of oxidative stress, and reduc- tion of lipid peroxidation [34]. Therefore, L-Carnitine plays a protective role in metabolic disorders. Virmani and Gaetani’s study [35] revealed that L-carnitine could maintain the MPT and modulate the activation of the mitochondrial permeabil- ity transition pores (mPTP), especially the cyclosporin-de- pendent mPTP. Furthermore, their preliminary experiments also showed that LC may reduce the peroxynitrite levels and protect against the underlying mechanism of methamphet- amine toxicity [36]. In this study, the hypothesis that enhancement of mi- tochondrial energy metabolism by using L-carnitine could prevent the generation of inﬂammatory factors and protect 82 Articles © The authors | Journal compilation © J Clin Med Res and Elmer Press™ | www.jocmr.org IL-1 195.52 ± 52.26Δ 601.29 ± 58.33* 291.58 ± 76.88 IL-6 259.89 ± 89.41Δ 567.25 ± 69.62* 258.75 ± 77.58 IL-10 359.38 ± 76.32Δ 126.06 ± 50.37* 254.65 ± 67.91 the integrality of mucosal barrier was tested. Moreover, the levels of TNF-α, IL-1β, IL-6, and IL-10 in serum (Table 4). The translocation of the E. Coli DH5α from extra-intestinal sites was examined in the study (Table 2) in order to obtain direct support for using L-carnitine that protects the intesti- nal barrier. In conclusion, the increase of L-carnitine density in IR intestine is a protective event. Mucosal injury and BT were reduced in the L-carnitine group, compared with the IR group (P less than 0.05). And L-carnitine effectively inhib- ited releasing of pro-inﬂammatory factors, compared with IR group (P less than 0.05). In addition, L-carnitine can protect intestine from IR injury because it can improve absorption of nutrients and prevention of BT. Nevertheless, clinical inves- tigations will be required in order to conﬁrm the effective- ness of L-carnitine as a therapeutic agent in clinical practice. References 1. Mojzis J, Hviscova K, Germanova D, Bukovicova D, Mirossay L. Protective effect of quercetin on ischemia/ reperfusion-induced gastric mucosal injury in rats. Physiol Res 2001;50(5):501-506. 2. Mallick IH, Yang W, Winslet MC, Seifalian AM. Isch- emia-reperfusion injury of the intestine and protective strategies against injury. Dig Dis Sci 2004;49(9):1359- 1377. 3. Guneli E, Cavdar Z, Islekel H, Sarioglu S, Erbayraktar S, Kiray M, Sokmen S, et al. Erythropoietin protects the intestine against ischemia/ reperfusion injury in rats. Mol Med 2007;13(9-10):509-517. 4. Teke Z, Kabay B, Aytekin FO, Yenisey C, Demirkan NC, Sacar M, Erdem E, et al. Pyrrolidine dithiocarba- mate prevents 60 minutes of warm mesenteric ischemia/ reperfusion injury in rats. Am J Surg 2007;194(2):255- 262. 5. Aldemir M, Gurel A, Buyukbayram H, Tacyildiz I. The effects of glucose-insulin-potassium solution and BN 52021 in intestinal ischemia-reperfusion injury. Vasc Endovascular Surg 2003;37(5):345-351.