The effects of L-carnitine on gastrointestinal contractility and histological changes in rat intestinal ischemia-reperfusion Injury / Efectos de la l-carnitina sobre la contractilidad gastrointestinal y los cambios histológicos en la lesión por isquemia-reperfusión intestinal de rata

SUMMARY: Ischemia-reperfusion (I/R) of the small intestine causes serious abdominal pathologies including tissue dysfunction and organ failure. L-carnitine (L-C), a powerful antioxidant, may help lessen the severity of these pathological effects since it plays a key role in energy metabolism. In this work we aimed to study the effects of L-C on the isolated ileal and duodenal contractility and histological changes in intestinal ischemia and reperfusion injury. Twenty eight Wistar rats were divided into four groups. The first group is the control group. Second group, I/R group, had rats submitted to 45-minutes of intestinal ischemia and to 45-minutes reperfusion. The third group, I/R+ L-C group, rats were treated with L-C 5 minutes before reperfusion and than submitted to ischemia. The fourth group, included rats that were treated with L-C without ischemia or reperfusion. Intestinal ischemia was conducted by obstructing superior mesentery arteries by silk loop. The ileal and duodenal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (Ach) and relaxation was achieved with phenylephrine. At the same time the terminal ileal and duodenal segments were examined for histological changes. Ach-induced contraction responses were higher in the I/R+L-C group, the L-C group, and the control group compared to the I/R group, in both ileal and duodenal segments. On the other hand, the phenylephrine-induced relaxations were higher in the I/R+L-C and L-C groups, especially in duodenal segments. In I/R group intestinal morphology was observed to be severely damaged whereas in I/R+L-C group the damage was noticeably lower possibly due to protective properties of L-C. I/R injury caused severe cellular damage response within the muscularis resulting in decreased gastrointestinal motility. Treatment with the L-C has significantly affected the gastrointestinal contractility. Also L-C treatment reduced the damage in intestinal morphology that occurs after IR injury.

RESUMEN: La isquemia-reperfusión (I/R) del intestino delgado provoca graves patologías abdominales que incluyen disfunción tisular y falla orgánica. La L-carnitina (L-C), un poderoso antioxidante, puede ayudar a disminuir la gravedad de estos efectos patológicos, ya que desempeña un papel clave en el metabolismo energético. El objetivo de este trabajo fue estudiar los efectos de L-C sobre la contractilidad ileal y duodenal aislada y los cambios histológicos en la lesión por isquemia y reperfusión intestinal. Se dividieron 28 ratas Wistar en cuatro grupos. El primer grupo fue el control. El segundo grupo, grupo I/R, de ratas sometidas durante 45 minutos de isquemia intestinal y a 45 minutos de reperfusión. El tercer grupo, grupo I/R+ L-C, las ratas se trataron con L-C, 5 minutos antes de la reperfusión y luego se sometieron a isquemia. El cuarto grupo, las ratas fueron tratadas con L-C sin isquemia ni reperfusión. La isquemia intestinal se realizó obstruyendo la arteria mesentérica superior con un asa de seda. Los segmentos ileal y duodenal se aislaron y suspendieron en un baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (Ach) y la relajación se logró con fenilefrina. Al mismo tiempo, se examinaron cambios histológicos de los segmentos del íleon terminal y del duodeno. Las respuestas de contracción inducidas por Ach fueron mayores en el grupo I/R+L-C, el grupo L-C y el grupo control en comparación con el grupo I/R, tanto en el segmento ileal como en el duodenal. Por otra parte, las relajaciones inducidas por fenilefrina fueron mayores en los grupos I/R+L-C y L-C, especialmente en los segmentos duodenales. En el grupo I/R se observó que la morfología intestinal estaba dañada significativamente, mientras que en el grupo I/R+L-C el daño fue notablemente menor, posiblemente debido a las propiedades protectoras de L-C. La lesión por I/R causó una respuesta de daño celular severo dentro de la capa muscular que resultó en una disminución de la motilidad gastrointestinal. El tratamiento con L-C afectó significativamente la contractilidad gastrointestinal. Por otra parte, el tratamiento L-C redujo el daño en la morfología intestinal que ocurre después de la lesión por IR.

Effects and molecular mechanism of exogenous L-carnitine on excessive endoplasmic reticulum stress-mediated hepatic pyroptosis in severely scald rats / 中华烧伤杂志

Objective: To investigate the effects and molecular mechanism of exogenous L-carnitine on hepatic pyroptosis mediated by excessive endoplasmic reticulum stress in severely scald rats. Methods: The experimental research method was adopted. According to the random number table (the same group method below), fifteen female Sprague Dawley rats aged 6-8 weeks were divided into sham-injury group, scald alone group, and scald+carnitine group (with 5 rats in each group), and full-thickness scald of 30% total body surface area were made on the back of rats in scald alone group and scald+carnitine group, and rats in scald+carnitine group were additionally given intraperitoneal injection of L-carnitine. At post injury hour (PIH) 72, The levels of aspartate aminotransferase (AST) and alanine dehydrogenase (ALT) of biochemical indicators of liver injury were detected by automatic biochemical analyzer with the sample number of 5. At PIH 72, liver tissue damage was detected by hematoxylin-eosin staining. At PIH 72, The mRNA levels of nucleotide-binding oligomerization domain-containing protein-like receptor family pyrin domain containing 3 (NLRP3), cysteine aspartic acid specific protease 1 (caspase-1), gasderminD (GSDMD), and interleukin 1β(IL-1β) in liver tissue as pyroptosis-related markers and glucose regulatory protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in liver tissue as endoplasmic reticulum stress-related markers were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR). Protein expression levels of GRP78, CHOP, NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue were detected by Western blotting, and the sample numbers were all 5. HepG2 cells as human liver cancer cells were divided into dimethyl sulfoxide (DMSO) group, 0.1 μmol/L tunicamycin (TM) group, 0.2 μmol/L TM group, 0.4 μmol/L TM group, and 0.8 μmol/L TM group and were treated accordingly. After 24 h of culture, cell viability was detected by cell counting kit 8, and the intervention concentration of TM was screened, and the sample number was 5. HepG2 cells were divided into DMSO group, TM alone group, and TM+carnitine group, and treated accordingly. After 24 h of culture, the protein expression levels of GRP78, CHOP, NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in cells were detected by Western blotting, and the sample numbers were all 3. Data were statistically analyzed with one-way analysis of variance and least significant difference-t test. Results: At PIH 72, the AST and ALT levels of serum in scald alone group were (640±22) and (157±8) U/L, which were significantly higher than (106±13) and (42±6) U/L in sham-injury group, respectively, with t values of -46.78 and -25.98, respectively, P<0.01. The AST and ALT levels of serum in scald+carnitine group were (519±50) and (121±10) U/L, which were significantly lower than those in scald alone group, respectively, with t values of 4.93 and 6.06, respectively, P<0.01. At PIH 72, the morphology of liver tissue of rats in sham-injury group were basically normal with no obvious inflammatory cell infiltration; compared with those in sham-injury group, the liver tissue of rats in scald alone group showed a large number of inflammatory cell infiltration and disturbed cell arrangement; compared with that in scald alone group, the liver tissue of rats in scald+carnitine group showed a small amount of inflammatory cell infiltration. At PIH 72, the mRNA expression on levels of NLRP3, caspase-1, GSDMD, and IL-1β in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 34.42, 41.93, 30.17, and 15.68, respectively, P<0.01); the mRNA levels of NLRP3, caspase-1, GSDMD, and IL-1β in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 34.40, 37.20, 19.95, and 7.88, respectively, P<0.01). At PIH 72, the protein expression levels of NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 12.28, 26.92, 5.20, 10.02, and 24.78, respectively, P<0.01); compared with those in scald alone group, the protein expression levels of NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue of rats in scald+carnitine group were significantly decreased (with t values of 10.99, 27.96, 12.69, 8.96, and 12.27, respectively, P<0.01). At PIH 72, the mRNA levels of GRP78 and CHOP in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 21.00 and 16.52, respectively, P<0.01), and the mRNA levels of GRP78 and CHOP in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 8.92 and 8.21, respectively, P<0.01); the protein expression levels of GRP78 and CHOP in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 22.50 and 14.29, respectively, P<0.01), and the protein expression levels of GRP78 and CHOP in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 14.29 and 5.33 respectively, P<0.01). After 24 h of culture, the cell survival rates of 0.1 μmol/L TM group, 0.2 μmol/L TM group, 0.4 μmol/L TM group, and 0.8 μmol/L TM group were significantly decreased than that in DMSO group (with t values of 4.90, 9.35, 18.64, and 25.09, respectively, P<0.01). Then 0.8 μmol/L was selected as the intervention concentration of TM. After 24 h of culture, compared with that in DMSO group, the protein expression levels of GRP78 and CHOP in cells in TM alone group were significantly increased (with t values of 10.48 and 17.67, respectively, P<0.01), and the protein expression levels of GRP78 and CHOP in TM+carnitine group were significantly lower than those in TM alone group (with t values of 8.08 and 13.23, respectively, P<0.05 or P<0.01). After 24 h of culture, compared with those in DMSO group, the protein expression levels of NLRP3 and GSDMD-N in cells in TM alone group were significantly increased (with t values of 13.44 and 27.51, respectively, P<0.01), but the protein expression levels of caspase-1, caspase-1/p20, and cleaved IL-1β in cells were not significantly changed (P>0.05); compared with that in TM alone group, the protein expression levels of NLRP3 and GSDMD-N in cells in TM+carnitine group were significantly decreased (with t values of 20.49 and 21.95, respectively, P<0.01), but the protein expression levels of caspase-1, caspase-1/p20, and cleaved IL-1β in cells were not significantly changed (P>0.05). Conclusions: In severely scald rats, exogenous L-carnitine may play a protective role against liver injury by inhibiting the pathways related to excessive endoplasmic reticulum stress-mediated pyroptosis.

Novo Efeito Cardioprotetor da L-Carnitina em Camundongos Obesos Diabéticos: Regulação da Expressão de Quemerina e CMKLRI no Coração e Tecidos Adiposos / Novel Cardioprotective Effect of L-Carnitine on Obese Diabetic Mice: Regulation of Chemerin and CMKLRI Expression in Heart and Adipose Tissues

Resumo Fundamentos A L-carnitina (LC) tem muitos efeitos benéficos em animais diabéticos e humanos, mas seu efeito regulatório sobre a quemerina como uma citocina inflamatória e seu receptor no estado diabético são desconhecidos. Objetivos O presente estudo teve como objetivo investigar o efeito regulatório da LC na expressão do receptor semelhante ao de quimiocina 1 e quemerina (CMKLRI) em tecidos adiposo e cardíaco de camundongos diabéticos. Métodos Sessenta camundongos NMARI foram divididos em quatro grupos, incluindo controle, diabético, diabético + suplementação com LC e controle + suplementação com LC. O diabetes foi induzido pela alimentação dos animais com dieta hipercalórica por 5 semanas e injeção de estreptozotocina. Os animais foram tratados com 300 mg/kg de LC por 28 dias. Nos dias 7, 14 e 28 após o tratamento, os níveis de mRNA e proteína da quemerina e CMKLRI nos tecidos cardíacos e adiposos de animais foram determinados utilizando análise por qPCR e ELISA. Os índices de resistência à insulina também foram medidos em todos os grupos experimentais. A diferença com p<0,05 foi considerada significativa. Resultados A expressão de quemerina e CMKLRI aumentou nos tecidos cardíaco e adiposo de camundongos diabéticos nos dias 14 e 28 após a indução do diabetes, concomitantemente com a incidência de resistência à insulina e níveis aumentados de quemerina circulante (p<0,05). O tratamento com LC causou uma diminuição significativa na expressão de ambos os genes nos tecidos estudados e redução dos sintomas de resistência à insulina e dos níveis séricos de quemerina (p<0,05). Conclusão Os resultados sugerem que o tratamento com LC pode diminuir a expressão de quemerina e CKLR1 em tecidos cardíacos e adiposos de animais experimentais obesos e diabéticos.

Abstract Background L-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown. Objectives The present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice. Methods Sixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant. Results Chemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05). Conclusion The results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.

Protective effect of L-carnitine on myocardial injury in rats with heatstroke

Abstract Purpose: To investigate the protective effect of L-carnitine on myocardial injury in rats with heatstroke. Methods: orty-eight rats were randomly divided into control, heatstroke and 25, 50 and 100 mg/kg L-carnitine groups. The last three groups were treated with 25, 50 and 100 mg/kg L-carnitine, respectively, for seven successive days. Then, except for the control group, the other four groups were transferred into the environment with ambient temperature of (39.5 ± 0.4 °C) and relative humidity of (13.5 ± 2.1%) for 2 h. The core temperature (Tc), mean arterial pressure (MAP), heart rate (HR) and serum and myocardial indexes were detected. Results: Compared with the heatstroke group, in the 100 mg/kg L-carnitine group, the Tc was significantly decreased, the MAP and HR were significantly increased, the serum creatine kinase, lactate dehydrogenase, alkaline phosphatase, aspartate aminotransferase, tumor necrosis factor α and interleukin 1β levels were significantly decreased, the myocardial superoxide dismutase and glutathione peroxidase levels were significantly increased, the myocardial malondialdehyde level was significantly decreased and the cardiomyocyte apoptosis index and myocardial caspase-3 protein expression level were remarkably decreased (p < 0.05). Conclusions: The L-carnitine pretreatment can alleviate the myocardial injury in heatstroke rats through reducing the inflammatory response, oxidative stress and cardiomyocyte apoptosis.

L-carnitine has a protective effect on the colonic mucosa during abdominopelvic radiotherapy in rats

ABSTRACT PURPOSE: To evaluate histopathologically the radioprotective effect of L-carnitine on the colonic mucosa in rats undergoing abdominopelvic irradiation. METHODS: Thirty-two rats were randomly assigned to four experimental groups: intraperitoneal administration of normal saline (group 1) or L-carnitine (300 mL/kg; group 2), followed in groups 3 and 4, respectively, by one dose of abdominopelvic radiation (20 Gy) 30 min later. Rats were sacrificed 5 days after radiation, and their descending colons were resected for histopathological evaluation of the presence and severity of damage. RESULTS: Average damage scores did not differ significantly between groups 1 and 2 (0.13 ± 0.35 and 0.25 ± 0.46, respectively); the group 3 score was highest (10.25 ± 0.71), and the group 4 score (3.63 ± 1.41) was significantly lower than that of group 3 (both p = 0.0001). Pre-radiation L-carnitine administration significantly reduced mucosal thinning, crypt distortion, reactive atypia, inflammation, cryptitis, and reactive lymph-node hyperplasia (all p < 0.01). CONCLUSIONS: L-carnitine had a radioprotective effect on rat colonic mucosa. L-carnitine use should be explored for patients with gastrointestinal cancer, who have reduced serum L-carnitine levels.

Effects of L-carnitine and L-acetyl-carnitine on testicular sperm motility and chromatin quality

Sperm cells extracted from testes [TESE] have poor chromatin quality and motility. Various substances are used in the laboratory to increase sperm motility and improve the ART outcomes; however, there are few research which considered improving both sperm motility and chromatin quality. The aim of this investigation was to evaluate the improvement of the testicular sperm motility and chromatin quality exposed to L-carnitine [LC] and L-acetyl-carnitine [LAC], which are normally concentrated in testis and epididymis, compared with Pentoxifylline [PF], which used for sperm motility enhancement in IVF procedures. TESE samples from 30 male mice divided into four parts. The sperm samples were added to Ham' F10 [control] or the media contained 1.76mM of LC, LAC or PF], then, the samples were kept in the room temperature for 30, 90 and 180 min. At each time step, sperm motility and chromatin quality were assessed. Chromatin quality was evaluated by chromomycin A3 and aniline blue. Statistical analysis was performed using one way analysis of variance [ANOVA]. A p-value less than 0.05 were accepted as a statistically significant difference. The results showed LC, LAC and PF significantly increased the sperm motility. However, sperm chromatin quality only improved significantly by administration of LC and LAC. Administration of LC and LAC to the testicular sperm samples can lead to improve both sperm motility and chromatin quality. It may be because they can mimic in vivo sperm condition during late spermatogenesis

Low dose gamma irradiation modifies the effect of L-carnitine, curcumin, garlic powder and green tea extract on doxorubicin-induced nephropathy in rats

The possible protective potential of exposure to low dose of gamma radiation in presence or absence of L-carnitine, curcumin, garlic powder or green tea extract was examined in the present study on doxorubicin [DOX]-induced experimental nephropathy in rats. Preliminary study was carried out to select the suitable dose of DOX to induce nephrotoxicity. In the current experiment 5 mg/kg, i.p. was selected as a single dose to induce nephrotoxicity during 15 days. The possible modulating effect of L-carnitine, curcumin, garlic powder or green tea extract on kidney function was examined. Animals were subdivided into three sets. Three groups of the 1[st] set were exposed to [gamma] radiation at a single dose level of 0.3 Gy then received DOX, 1, 3 or 7 days postirradiation respectively. The groups of 2[nd] set daily received L-carnitine [40 mg/kg, i.p.], curcumin [50 mg/kg, i.p.], garlic powder [100 mg/kg, p.o.] and green tea extract [300 mg/kg, p.o.] daily for two weeks before induction of nephropathy. Groups of the 3[rd] set received the same doses of drugs then were injected with DOX, 1, 3 or 7 days following gamma irradiation respectively. Two groups of animals, one of them received saline and served as normal and the other received DOX and served as nephropathic group were included in 1[st], 2[nd] as well as 3[rd] set. Fifteen days following DOX administration, serum was collected and the animals were then sacrificed. Serum creatinine, urea and uric acid were evaluated. Data revealed that, a single DOX dose [5 mg/kg] induced marked acute nephrotoxicity manifested as significant increase in the activities of serum creatinine, urea as well as uric acid. Interestingly, pre-exposure to gamma radiation at a dose level of 0.3 Gy, 1 or 3 days before DOX injection exhibited significant improvement in the above altered mentioned parameters. However, exposure to low dose radiation 7 days prior to DOX administration did not show a protective effect. Moreover, pretreatment with L-carnitine, curcumin, garlic powder or green tea extract in rats unexposed or exposed to gamma radiation before DOX administration ameliorated, to a great extent, the effects induced by DOX. The present findings suggest that exposure to a single low dose of gamma radiation [0.3 Gy] one day before DOX administration is a promising approach for maximizing the nephroprotective effects of L-carnitine, curcumin, garlic powder or green tea extract with minimal adverse effects of DOX

[Effect of L-carnitine supplement on semen parameters in men with idiopathic infertility]

It is proposed that L-carnitine is a useful agent for treatment of various dysfunctions of sperm in infertile men. So, in the present study, effect of L-carnitine supplement on sperm parameters in men with idiopathic infertility was evaluated. Thirty infertile men, aged between 20 and 40 years, with the following baseline sperm selection criteria, including sperm count< 66.6 x 10[6], motility< 30%, viability< 60%, normal morphology< 35%, were studied. Patients received 3 gram per day L-carnitine for six months. Semen analysis was performed according to World Health Organization guidelines before study, and 3 and 6 months of therapy. Sperm parameters included liquefaction, pH, volume, sperm count, motility, viability and normal morphology. The results showed that L-carnitine supplementation increased significantly sperm count, motility, viability and normal morphogy and pregnancy rate after 3 months [p<0.01] and 6 months [p<0.001]. Also, L-carnitine supplementation increased sperm motility and viability in idiophatic infertile men after 3 and 6 months [p<0.001]. Five couples became pregnant during the study. The present study indicated that L-carnitine supplementation is an appropriate drug in the treatment of men with idiopathic infertility

Effects of L-carnitine added to erythropoietin in anemic chronic renal failure patients on Hemodialysis

Chronic renal disease [C.R.D] is a pathophysiological process due to progressive and irreversible decrease in number and function of nephrons in the kidney. Anemia is one of the most important complications in CRD patients. Anemia is caused mainly due to diminished production of erythropoietin [EPO], which is treated by weekly injection of the EPO. L-carnitine added to EPO can increase the efficacy of EPO. Present study, from March 2003 until September 2004 [18 months], evaluates the effects of L-carnitine added to EPO in 30 patients at Shaheed Rahnemon hemodialysis center of Yazd. Each patient was administered one oral table [250 mg] of L-carnitine, twice a day along with EPO for 90 days. EPO was in the form of injection 2000 iu/sc after dialysis. [three times per week]. One questionnaire was completed for each patient, which included demographic characteristics, type of disease, duration of the hemodialysis, Hb and Hct levels, transferrin saturation and ferritin levels. Hb, Hct and transferrin saturations were measured on days 1, 45 and 90. Results were analyzed by paired t test and analysis of variance. Results of this study showed that the mean Hb levels and Hct were significantly raised up to 1.1 mg/dl [P. value<0.001] and 2.7% [P.Value<0.001], respectively. In addition, significant decrease of 5.75% in transferrin [P.Value< 0.001] and 121 ng/ml in ferritin levels [P.Value< 0.001] was observed. Efficacy of EPO plus L-carnitine was affected only by duration of hemodialysis and not by age, sex or causes of CRD. L-carnitine added to EPO increases the efficacy of EPO after 3 months

L-Carnitine ameliorates immunological-induced hepatitis in rats

Immunological mediated hepatitis can be initiated by bacterial product; Lipopolysaccharide [LPS]. The later is increased during severe infection, bacterial overgrowth or translocation. LPS stimulates Kupffer cells. Activation of the kupffer cells contributes to the onset of liver injuries by producing and releasing cytotoxic agents, inflammatory cytokines and reactive oxygen species. In the present study, L-carnitine, a natural antioxidant and immunoprotective agent, is used to protect against LPS-induced hepatitis. Liver content of glutathione [GSH], malondialdehyde [MDA], nitric oxide [NO] and the DNA adduct S-hydroxydeoxyguanosine [8-HDG] are estimated. Serum activity of liver enzymes ALT, AST, and Gamma-GT, in addition to IL2 level are also estimated. Moreover, liver histopathological changes are determined. Results revealed that LPS [5mg/kg once i.p] significantly increased 8-HDG, MDA, NO and depleted GSH in the liver of the treated rats. It also, increased serum 1L2 and activity of all the estimated liver enzyme markers indicating massive hepatic cellular damage as also shown as a necrotic damage in liver histological sections. LCR administered [500 mg/kg] 3h before LPS protected against LPS-induced lethality by 100%. LCR also prevented the increase in liver content of 8-HDG, MDA and NO. It rescued the depleted GSH and prevented the necrotic damage in the liver tissue as shown by normalization of ALT, AST and Gamma-GT as well as IL2 and a remarkable improvement in liver histology. These data suggest that LCR could be used as an adjuvant therapy in severely infected and septic patients to counteract LPS-induced liver hepatitis

Effects of ICRF-187 and L-carnitine on bleomycin-induced lung toxicity in rats

The possible modulatory effects of ICRF-187 and L-carnitine against bleomycin -induced pulmonary toxicity in male rats were investigated. Repeated administration of bleomycin [10mg/kg, twice weekly for 6 consecutive weeks] produced significant lung toxicity. The toxicity was manifested by significant increase in normal contents of lipid peroxide [LPO. 91.7%], reduced glutathione [GSH, 73.2%] and oxidised glutathione [GSSG, 135,4%] as well as the activity of superoxide dismutase [SOD, 222.7%]. Thirty minutes prior to bleomycin treatment, other groups of rats were received either ICRF-187 [95 mg/kg] or L-carnitine [500 mg/kg] adopting the same schedule of treatment as in bleomycin-treated group. L-carnitine decreased bleomycin-induced elevations in SOD activity, GSH and GSSG contents, however, it failed to suppress the increase in LPO level. On the other hand,. treatment with ICRF-187 returned back all the elevated biochemical parameters induced by bleomycin to nearly normal levels. In conclusion, the results of this study showed a potential capability of ICRF-187 to mitigate the bleomycin-induced lung injury. Moreover, despite the inability of L-carnitine to change the elevated LPO content, it was able however, to decrease the elevated endogenous antioxidant parameters

Protective effect of L-carnitine on gastric mucosal barrier in rats exposed to cold-restraint stress.

AIM: The protective effect of L-carnitine on stress-induced gastric mucosal injury was investigated in rats exposed to cold-restraint stress (CRS). METHODS: The animals were divided into four groups. Groups 1 and 3 received saline by intragastric gavage for 10 days. Groups 2 and 4 received L-carnitine (50 mg/Kg/day) in the same manner. Groups 3 and 4 were exposed to CRS in the form of immobilization at 4 degrees C for 4 h on day 10. Ulcer index, gastric acid secretion and hemoglobin leakage, and gastric mucosal mucin and PGE2 content were measured. RESULTS: In rats exposed to CRS, as compared to control rats (group 1), ulcer index was higher, gastric acid production was lower, hemoglobin leakage into the gastric lumen was increased, and gastric mucosal mucin and PGE content were reduced. L-carnitine treatment prior to CRS led to attenuation of changes in ulcer index, gastric acid secretion, amount of hemoglobin leakage into the gastric lumen and gastric PGE2 content. In rats receiving L-carnitine but not exposed to CRS, gastric acid secretion, mucin and PGE2 content of gastric mucosa were similar to those in control rats. CONCLUSION: L-carnitine decreases CRS-induced gastric mucosal injury.

Does left ventricular function improve with L-carnitine after acute myocardial infarction?

A double blind randomized placebo controlled clinical trial was carried out to assess the efficacy and safety of L-carnitine in patients suffering from acute anterior wall myocardial infarction with respect to left ventricular function. Sixty patients (34 men, 26 women, mean age 56+11 yr.) with acute anterior wall myocardial infarction were randomized to placebo and L-carnitine. All the patients were given intravenous L-carnitine / placebo in the dose of 6gm/day for the first seven days followed by oral L-carnitine / placebo 3 gm/day in three divided doses for a period of three months. Echocardiography was performed for regional wall motion abnormality, left ventricular end systolic volume (ESV), end diastolic volume (EDV) and ejection fraction (EF) on admission, after seven days and after three months of the infarction. Forty-four patients completed the study. There were three deaths, two in the placebo and one in the L-carnitine group (p>0.05). Thirteen patients were lost to follow up. Echo parameters in both groups were comparable (p>0.05). The duration of chest pain prior to initiation of the I.V. L-carnitine was 7.5 + 5.2 hrs in the L-carnitine group and 7 + 4 hrs in the placebo group (p>0.05). There was no statistical difference in the EF, ESV and EDV on admission, at discharge and after three months in the L-carnitine and the placebo groups (p>0.05). No significant adverse effects were noted. L-carnitine, though a safe drug, does not affect the left ventricular function in patients with myocardial infarction.

Valproic acid-induced hepatotoxicity and protective role of carnitine

Valproic acid [valproate; VPA] is a first line drug for use in epilepsy. Often the handicapped/ epileptic children are undernourished in developing countries. Valproic acid reduces serum carnitine which is an essential cofactor in transport of long chain fatty acids across the inner mitochondrial membrane. Low serum carnitine and malnourishment can cause fatty infiltration and hepatotoxicity leading to a Reye-like syndrome and/or fulminant hepatic failure. In an experimental study on rats treated with therapeutic/toxic doses of valproic acid supplemented by carnitine, we have found that valproic acid alone caused fatty infiltration and necrosis of the liver while carnitine supplementation prevented these events. It is suggested that valproic acid therapy be supplemented with canitine in epileptic patients and liver function profile must be regularly monitored in these patients. Adequate intake of carnitine must be ensured in growing infants and children

Effect of carnitine on malondialdehyde, taurine and glutathione levels in heart of rats subjected to myocardial stress by isoproterenol.

The effect of carnitine on free fatty acid, malondialdehyde, taurine and glutathione levels in myocardium was studied in rats administered isoproterenol to induce a stress in the myocardium resulting in myocardial ischaemia. Carnitine decreased the levels of free fatty acid and malondialdehyde (an index of lipid peroxidation) when compared to control rats given isoproterenol alone. Taurine and glutathione also registered a fall in the carnitine treated animals when compared to rats treated with isoproterenol alone. The results indicate that carnitine by decreasing the levels of these parameters helps the myocardium to survive from the stress induced by isoproterenol.