Acta Anaesthesiologica Scandinavica ISSN: EISSN: Page Numbers. This enhanced oxidative stress leads to cell damage resulting in various complications such as sepsis, myocardial injury and increased mortality. The aim of this study was to investigate the role of antioxidant treatment with l-carnitine in oxidative stress and platelet activation in patients undergoing major abdominal surgery.

METHODS: Forty patients scheduled for abdominal surgery were randomly allocated to l-carnitine, administered with a rapid infusion 0. placebo treatment just before the surgical intervention. verfasst von Bor-Jen Lee Jun-Shuo Lin Yi-Chin Lin Ping-Ting Lin.

Publikationsdatum Verlag BioMed Central. Research An anti-inflammatory diet as treatment for inflammatory bowel disease: a case series report. Letter to the Editor Fructose in obesity and cognitive decline: is it the fructose or the excess energy?

Research The impact of waist circumference on function and physical activity in older adults: longitudinal observational data from the osteoarthritis initiative. Research Modern diet and metabolic variance - a recipe for disaster? E Cell viability was detected by Cell Counting kit-8 assay.

CDK, cyclin-dependent kinase; COX2, cyclooxygenase-2; H2O2, hydrogen peroxide; LC, L-carnitine; P-, phosphorylated; PCNA, proliferating cell nuclear antigen.

Intracellular ROS activates p38 MAPK, an oxidative sensor that belongs to the MAPK family 18 ; therefore, to decipher the potential cellular mechanism underlying the effects of LC on oxidative damage, this study evaluated whether the MAPK signaling pathway was involved.

As determined by western blot analysis Fig. To further evaluate the role of the MAPK signaling pathway in mediating the protective effects of LC on H 2 O 2 -induced cell inhibition and inflammation, cell viability and COX-2 expression was assessed in cells exposed to H 2 O 2 and LC in the presence of an ERK inhibitor FR or p38 inhibitor PD Furthermore, pretreatment with FR or PD abolished H 2 O 2 -induced COX-2 expression.

In addition, HLE B-3 cells exposed to H 2 O 2 and LC combined with FR or PD exhibited considerably increased cell viability Fig. These results indicated that LC may exert beneficial effects against oxidative damage via MAPK signaling.

Oxidative stress is a risk factor for cataracts caused by the overproduction of ROS. H 2 O 2 is a main type of ROS that leads to oxidative damage in HLECs. Antioxidants that scavenge excess ROS serve as a defense against cell damage In this study, it was demonstrated that LC exhibited minimal cytotoxicity and reversed H 2 O 2 -induced ROS production.

Exposure of HLE B-3 cells to H 2 O 2 triggered oxidative damage, which was reflected in the destructed antioxidant defense mechanism. Antioxidant substances, including FoxO1, PRDX4 and CAT, are involved in ROS scavenging and serve as potential protectors.

H 2 O 2 -induced oxidative damage is associated with decreased FoxO1, PRDX4 and CAT activities 20 , 21 , indicating the probable mechanisms underlying cataract formation. The present study focused on the oxidative damage caused by ROS imbalance; therefore, FoxO1, PRDX4 and CAT were detected as antioxidative substances.

FoxO1 is highly expressed as a downstream antioxidant when activated The present study revealed that FoxO1 is highly expressed in HLECs treated with LC, suggesting that LC possesses antioxidative potential.

The present results indicated that LC may exert beneficial effects on ROS scavenging by increasing the expression levels of the antioxidative enzymes CAT and PRDX4. This finding is consistent with previous findings, which suggested that LC may protect retinal pigment epithelial cells from H 2 O 2 -induced oxidative damage by increasing antioxidant and antioxidant enzyme activity This study hypothesized that LC may act as a potential antioxidant protector against cataract formation.

Our future study aims to further explore alterations in transcriptional regulation and the potential underlying mechanism. In addition, further studies are required to determine the optimal therapeutic delivery method of LC to the lens.

Notably, widely used topical inserts and colloidal drug delivery systems 24 , such as nanowafers 25 , may represent possible pharmacological vehicles to enhance therapeutic efficacy.

PCNA is an auxiliary protein that facilitates cell cycle progression. In this study, PCNA, CDK2 and CDK4 expression were enhanced by LC in the presence of H 2 O 2 , demonstrating the role of LC in protecting HLECs against oxidative damage.

Given its antioxidant properties, LC may promote the cell cycle and thereby increase cell proliferation. Exposure to H 2 O 2 may promote EMT in the transparent lens. In this study, marked decreases in the expression of the epithelial marker AQP1, together with an increase in mesenchymal markers vimentin and α-SMA , were observed in HLECs exposed to H 2 O 2.

Prevention of EMT was demonstrated by elevated AQP1 expression, and attenuated vimentin and α-SMA expression in the presence of LC.

This result is consistent with a previous study suggesting that LC prevents the expression of EMT-associated biomarkers in renal fibrosis It was hypothesized that LC may become activated in response to ROS production and scavenging; however, the exact mechanisms require further analysis.

Oxidative stress is closely associated with inflammatory processes, which are important for the initiation and progression of cataracts 29 , The expression of proinflammatory cytokines, including IL-1β, IL6 and IL8, was reduced by LC pretreatment. COX2 is a major oxygenase, and its expression increases along with oxidative stress-induced inflammation This study further revealed that the production of COX2 was markedly induced by H 2 O 2 , but significantly rescued by LC.

Inflammation triggers LECs to undergo an apoptotic response and subsequently initiate cataract formation Cleaved-caspase-3 expression was decreased and inflammation was inhibited upon LC exposure.

In the present study, it was revealed that H 2 O 2 may act as a mediator of inflammation and apoptosis in HLECs, whereas LC could significantly attenuate inflammation and reduce apoptosis of HLECs. It has been reported that MAPK pathway inhibitors can regulate apoptosis and inflammatory responses.

The present results revealed that ERK and p38 inhibitors significantly reduced H 2 O 2 -induced cytotoxicity and inhibited the expression of the inflammatory cytokine COX2 induced by exposure to H 2 O 2. These findings provide insight into how oxidative modification of LC contributes to cataract prevention.

In conclusion, the protective effects of LC against oxidative stress may be attributed to its ROS-scavenging ability.

The obtained results suggested that LC may serve an important role in protecting HLECs from peroxidative damage and may be a promising therapeutic modality for the treatment of cataracts. The authors would like to thank Ms. Ruifang Han, Mr. Ming Ying and Mr.

Peng Hao Tianjin Key Laboratory of Ophthalmology and Visual Science for their technical assistance. This study was supported in part by the National Nature Science Foundation of China grant no. XY and HL made substantial contributions to the concept and design of the present study.

XL, FM, XH and LW performed the experiments. XL analyzed the data and wrote the paper. All authors read and approved the final manuscript.

Biol Pharm Bull. Invest Ophthalmol Vis Sci. Chang D, Zhang X, Rong S, Sha Q, Liu P, Han T and Pan H: Serum antioxidative enzymes levels and oxidative stress products in age-related cataract patients.

Oxid Med Cell Longev. Mok JW, Chang DJ and Joo CK: Antiapoptotic effects of anthocyanin from the seed coat of black soybean against oxidative damage of human lens epithelial cell induced by H 2 O 2.

Curr Eye Res. Fujii J, Ikeda Y, Kurahashi T and Homma T: Physiological and pathological views of peroxiredoxin 4. Free Radic Biol Med. Yamada S and Guo X: Peroxiredoxin 4 PRDX4 : Its critical in vivo roles in animal models of metabolic syndrome ranging from atherosclerosis to nonalcoholic fatty liver disease.

Pathol Int. Arch Pharm Res. View Article : Google Scholar. Kubo E, Shibata T, Singh DP and Sasaki H: Roles of TGF β and FGF signals in the lens: Tropomyosin regulation for posterior capsule opacity.

Int J Mol Sci. Lamouille S, Xu J and Derynck R: Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. Schey KL, Petrova RS, Gletten RB and Donaldson PJ: The role of aquaporins in ocular lens homeostasis. Dahm R: Dying to see. Sci Am. Traina G: The neurobiology of acetyl-L-carnitine.

Front Biosci Landmark Ed. Nutrients Editorial Office: Erratum: l-Carnitine supplementation in recovery after exercise; Nutrients , 10, Mishra A, Reddy IJ, Gupta PS and Mondal S: L-carnitine mediated reduction in oxidative stress and alteration in transcript level of antioxidant enzymes in sheep embryos produced in vitro.

Reprod Domest Anim. Deng R, Su Z, Hua X, Zhang Z, Li DQ and Pflugfelder SC: Osmoprotectants suppress the production and activity of matrix metalloproteinases induced by hyperosmolarity in primary human corneal epithelial cells.

Mol Vis. Mitchell SL, Uppal K, Williamson SM, Liu K, Burgess LG, Tran V, Umfress AC, Jarrell KL, Cooke Bailey JN, Agarwal A, et al: The carnitine shuttle pathway is altered in patients with neovascular age-related macular degeneration. Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2 -Delta Delta C T method.

Werner E, Wang H and Doetsch PW: Opposite roles for p38MAPK-driven responses and reactive oxygen species in the persistence and resolution of radiation-induced genomic instability. PLoS One. Bai J, Yang F, Dong L and Zheng Y: Ghrelin protects human lens epithelial cells against oxidative stress-induced damage.

Akasaki Y, Alvarez-Garcia O, Saito M, Caramés B, Iwamoto Y and Lotz MK: FoxO transcription factors support oxidative stress resistance in human chondrocytes. Arthritis Rheumatol.

Jump to main content. Contact Us. Citation Tags HERO ID. Reference Type. Journal Article. Effect of L-carnitine on oxidative stress and platelet activation after major surgery. Author s. Pignatelli, P; Tellan, G; Marandola, M; Carnevale, R; Loffredo, L; Schillizzi, M; Proietti, M; Violi, F; Chirletti, P; Delogu, G.

Is Peer Reviewed? In addition, LC exerted an ameliorating effect on H 2 O 2 -induced suppression of cell viability; however, this effect was not dose-dependent Fig.

Notably, cell viability was reduced to some extent when exposed to µ M LC alone; therefore, LC concentrations at , and µ M were chosen for subsequent experiments. Effects of LC on H2O2-induced reductions in HLE B-3 cell viability; cell viability was assessed by Cell Counting kit-8 assay.

A Cells were cultured with the indicated concentrations of H2O2 for 24 h. B Cells were cultured with the indicated concentrations of LC for 24 h. Cell viability was slightly inhibited by µM LC. C Cells were pretreated with LC at the indicated concentrations for 16 h and were then incubated with µM H2O2 for 24 h.

The reduction in HLE B-3 cell viability induced by H2O2 was restored by LC. H2O2, hydrogen peroxide; LC, L-carnitine. To determine the role of LC in ROS-induced oxidative damage, HLE B-3 cells were exposed to H 2 O 2 with or without LC pretreatment.

This study aimed to determine whether exposure to H 2 O 2 and LC could modify ROS generation. A marked increase in DCF-positive cells was observed by fluorescence microscopy in HLE B-3 cells exposed to H 2 O 2 , as shown in Fig.

DCF fluorescence was markedly reduced by LC pretreatment, thus suggesting that LC partially restrained H 2 O 2 -induced ROS generation in cells induced by H 2 O 2.

Effects of LC on ROS accumulation and FoxO1, PRDX4 and CAT expression. A Increased ROS levels induced by H2O2 were reversed by LC treatment in a concentration-dependent manner.

Scale bar, µm. B Reverse transcription-quantitative PCR analysis of the mRNA expression levels of FoxO1, PRDX4 and CAT. Compared with the H2O2 group, FoxO1, PRDX4 and CAT mRNA levels were upregulated by the indicated LC treatment.

C Western blot analysis of PRDX4. PRDX4 protein levels were significantly elevated in the presence of LC. Gray values were calculated for semi-quantification. CAT, catalase; FoxO1, forkhead box O1; H2O2, hydrogen peroxide; LC, L-carnitine; PRDX4, peroxiredoxin 4; ROS, reactive oxygen species.

As shown in Fig. Similar results were obtained by western blotting to detect PRDX4 protein expression Fig. These findings indicated that LC may exert protective effects on cells suffering from oxidative damage.

Cleaved-caspase-3 was detected as a marker of apoptosis; its expression was increased in HLECs exposed to H 2 O 2. Conversely, pretreatment with LC partially reversed the increase in cleaved-caspase-3 mRNA and protein expression Fig. Notably, compared with in the control group, H 2 O 2 exposure induced a ~1.

LC inhibits H2O2-induced inflammation and apoptosis. A Reverse transcription-quantitative PCR analysis revealed that caspase-3, COX2, IL1, IL6 and IL8 levels were reduced by the indicated LC treatment compared with in the H2O2 group. B Western blot analysis demonstrated that cleaved-caspase-3 and IL-1β levels were reduced by the indicated LC treatment.

COX2, cyclooxygenase-2; H2O2, hydrogen peroxide; IL, interleukin; LC, L-carnitine. The mRNA expression levels of inflammatory markers COX2, IL1, IL6 and IL8 were increased with H 2 O 2 exposure Fig.

LC reversed the inflammatory reaction induced by H 2 O 2 exposure; however, the effects were not dose-dependent.

Western blot analysis revealed that the protein expression levels of IL-1β were increased following H 2 O 2 treatment, whereas these levels were reduced by LC pretreatment Fig. Taken together, these data indicated that LC may have a role in reducing H 2 O 2 -induced apoptosis via alleviating inflammatory responses.

The expression levels of EMT-associated genes were detected in HLE B-3 cells exposed to H 2 O 2. The expression levels of AQP1, an epithelial marker, were reduced by H 2 O 2. Western blot analysis further verified the effects of H 2 O 2 and LC on the protein expression levels of vimentin, thus indicating that LC inhibited ROS-induced EMT Fig.

Effects of LC on EMT induced by oxidative stress. A Reverse transcription-quantitative PCR analysis revealed that AQP1 expression was increased, whereas vimentin and α-SMA expression was decreased by LC pretreatment compared with in the H2O2 group.

B Western blot analysis confirmed that vimentin expression was decreased by LC; however, the response was not dose-dependent. α-SMA, α-smooth muscle actin; AQP1, aquaporin 1; H2O2, hydrogen peroxide; LC, L-carnitine.

Subsequently, the modulatory effects of LC on proliferative markers were analyzed. LC pretreatment increased PCNA expression at the mRNA and protein levels compared with in the H 2 O 2 group Fig.

CDK2 and CDK4 mRNA expression was reduced upon H 2 O 2 exposure, whereas LC restored their expression Fig. LC restores cell proliferation and regulates cell damage through the MAPK pathway.

A Relative mRNA expression levels of PCNA, CDK2 and CDK4 were normalized to GAPDH. Compared with in the H2O2 group, PCNA, CDK2 and CDK4 mRNA expression was upregulated by LC pretreatment. B and C PCNA, ERK1 and ERK2, P-ERK1 and P-ERK2, p38 and p-p38 levels were assessed by western blotting. PCNA was upregulated by the indicated LC treatment, whereas p-p38, P-ERK1 and P-ERK2 were downregulated by LC treatment compared with in the H2O2 group.

D and E Human lens epithelial cells were pretreated with LC µM , ERK inhibitor FR, 1. D COX2 protein levels were measured using western blotting. Gray values were calculated for quantification.

E Cell viability was detected by Cell Counting kit-8 assay. CDK, cyclin-dependent kinase; COX2, cyclooxygenase-2; H2O2, hydrogen peroxide; LC, L-carnitine; P-, phosphorylated; PCNA, proliferating cell nuclear antigen. Intracellular ROS activates p38 MAPK, an oxidative sensor that belongs to the MAPK family 18 ; therefore, to decipher the potential cellular mechanism underlying the effects of LC on oxidative damage, this study evaluated whether the MAPK signaling pathway was involved.

As determined by western blot analysis Fig. To further evaluate the role of the MAPK signaling pathway in mediating the protective effects of LC on H 2 O 2 -induced cell inhibition and inflammation, cell viability and COX-2 expression was assessed in cells exposed to H 2 O 2 and LC in the presence of an ERK inhibitor FR or p38 inhibitor PD Furthermore, pretreatment with FR or PD abolished H 2 O 2 -induced COX-2 expression.

In addition, HLE B-3 cells exposed to H 2 O 2 and LC combined with FR or PD exhibited considerably increased cell viability Fig. These results indicated that LC may exert beneficial effects against oxidative damage via MAPK signaling.

Oxidative stress is a risk factor for cataracts caused by the overproduction of ROS. H 2 O 2 is a main type of ROS that leads to oxidative damage in HLECs. Antioxidants that scavenge excess ROS serve as a defense against cell damage In this study, it was demonstrated that LC exhibited minimal cytotoxicity and reversed H 2 O 2 -induced ROS production.

Exposure of HLE B-3 cells to H 2 O 2 triggered oxidative damage, which was reflected in the destructed antioxidant defense mechanism. Antioxidant substances, including FoxO1, PRDX4 and CAT, are involved in ROS scavenging and serve as potential protectors.

H 2 O 2 -induced oxidative damage is associated with decreased FoxO1, PRDX4 and CAT activities 20 , 21 , indicating the probable mechanisms underlying cataract formation. The present study focused on the oxidative damage caused by ROS imbalance; therefore, FoxO1, PRDX4 and CAT were detected as antioxidative substances.

FoxO1 is highly expressed as a downstream antioxidant when activated The present study revealed that FoxO1 is highly expressed in HLECs treated with LC, suggesting that LC possesses antioxidative potential.

The present results indicated that LC may exert beneficial effects on ROS scavenging by increasing the expression levels of the antioxidative enzymes CAT and PRDX4. This finding is consistent with previous findings, which suggested that LC may protect retinal pigment epithelial cells from H 2 O 2 -induced oxidative damage by increasing antioxidant and antioxidant enzyme activity This study hypothesized that LC may act as a potential antioxidant protector against cataract formation.

Our future study aims to further explore alterations in transcriptional regulation and the potential underlying mechanism. In addition, further studies are required to determine the optimal therapeutic delivery method of LC to the lens. Notably, widely used topical inserts and colloidal drug delivery systems 24 , such as nanowafers 25 , may represent possible pharmacological vehicles to enhance therapeutic efficacy.

PCNA is an auxiliary protein that facilitates cell cycle progression. In this study, PCNA, CDK2 and CDK4 expression were enhanced by LC in the presence of H 2 O 2 , demonstrating the role of LC in protecting HLECs against oxidative damage.

Given its antioxidant properties, LC may promote the cell cycle and thereby increase cell proliferation. Exposure to H 2 O 2 may promote EMT in the transparent lens.

In this study, marked decreases in the expression of the epithelial marker AQP1, together with an increase in mesenchymal markers vimentin and α-SMA , were observed in HLECs exposed to H 2 O 2. Prevention of EMT was demonstrated by elevated AQP1 expression, and attenuated vimentin and α-SMA expression in the presence of LC.

This result is consistent with a previous study suggesting that LC prevents the expression of EMT-associated biomarkers in renal fibrosis It was hypothesized that LC may become activated in response to ROS production and scavenging; however, the exact mechanisms require further analysis. Oxidative stress is closely associated with inflammatory processes, which are important for the initiation and progression of cataracts 29 , The expression of proinflammatory cytokines, including IL-1β, IL6 and IL8, was reduced by LC pretreatment.

COX2 is a major oxygenase, and its expression increases along with oxidative stress-induced inflammation This study further revealed that the production of COX2 was markedly induced by H 2 O 2 , but significantly rescued by LC. Inflammation triggers LECs to undergo an apoptotic response and subsequently initiate cataract formation Cleaved-caspase-3 expression was decreased and inflammation was inhibited upon LC exposure.

In the present study, it was revealed that H 2 O 2 may act as a mediator of inflammation and apoptosis in HLECs, whereas LC could significantly attenuate inflammation and reduce apoptosis of HLECs.

It has been reported that MAPK pathway inhibitors can regulate apoptosis and inflammatory responses. The present results revealed that ERK and p38 inhibitors significantly reduced H 2 O 2 -induced cytotoxicity and inhibited the expression of the inflammatory cytokine COX2 induced by exposure to H 2 O 2.

These findings provide insight into how oxidative modification of LC contributes to cataract prevention. In conclusion, the protective effects of LC against oxidative stress may be attributed to its ROS-scavenging ability. The obtained results suggested that LC may serve an important role in protecting HLECs from peroxidative damage and may be a promising therapeutic modality for the treatment of cataracts.

The authors would like to thank Ms. Ruifang Han, Mr. Ming Ying and Mr. Peng Hao Tianjin Key Laboratory of Ophthalmology and Visual Science for their technical assistance. This study was supported in part by the National Nature Science Foundation of China grant no.

XY and HL made substantial contributions to the concept and design of the present study. XL, FM, XH and LW performed the experiments. XL analyzed the data and wrote the paper. All authors read and approved the final manuscript. Biol Pharm Bull.

Invest Ophthalmol Vis Sci. Chang D, Zhang X, Rong S, Sha Q, Liu P, Han T and Pan H: Serum antioxidative enzymes levels and oxidative stress products in age-related cataract patients.

Oxid Med Cell Longev. Mok JW, Chang DJ and Joo CK: Antiapoptotic effects of anthocyanin from the seed coat of black soybean against oxidative damage of human lens epithelial cell induced by H 2 O 2.

Curr Eye Res. Fujii J, Ikeda Y, Kurahashi T and Homma T: Physiological and pathological views of peroxiredoxin 4. Free Radic Biol Med. Yamada S and Guo X: Peroxiredoxin 4 PRDX4 : Its critical in vivo roles in animal models of metabolic syndrome ranging from atherosclerosis to nonalcoholic fatty liver disease.

Pathol Int. Arch Pharm Res. View Article : Google Scholar. Kubo E, Shibata T, Singh DP and Sasaki H: Roles of TGF β and FGF signals in the lens: Tropomyosin regulation for posterior capsule opacity.

Int J Mol Sci. Lamouille S, Xu J and Derynck R: Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. Schey KL, Petrova RS, Gletten RB and Donaldson PJ: The role of aquaporins in ocular lens homeostasis.

Dahm R: Dying to see. Sci Am. Traina G: The neurobiology of acetyl-L-carnitine. Front Biosci Landmark Ed. Nutrients Editorial Office: Erratum: l-Carnitine supplementation in recovery after exercise; Nutrients , 10,