Administration Of L-carnitine Research Articles

Research of changes in the level of vascular endothelial growth factor in experimental diabetic retinopathy. comparison of methods of correction

The aim of work to investigate the changes in the vascular endothelium growth factor in experimental animals, which were simulated diabetic retinopathy and against the background of its correction.
 The results of the analysis of the vascular growth factor in the 2nd group confirm the development of diabetic retinopathy, a particularly pronounced increase in the marker was detected on the 180th day of the development of the pathological process. It was established analyzing the data of group No. 3 that the correction of the pathological condition with hypoglycemic agents has partial positive effect but requires the involvement of additional means of correction in addition to the normalization of the level of glycemia. The results of the 4th group indicate that the involvement of a nitric oxide donor and aflibercept in the correction of diabetic retinopathy has positive effect on the reduction of the level of vascular growth factor, more pronounced compared to the 3rd group, but it does not reach normative values. It is observed that the correction of the simulated pathological condition by reducing hyperglycemia, administration of aflibercept and bromfenac (group No. 5) gives positive results, but less pronounced, compared to the data of the 4th group.
 It was found that in rats in which diabetic retinopathy was modeled with subsequent correction of hyperglycemia, administration of aflibercept, L-carnitine and bromfenac (group No. 6) at the first stage, there is a pronounced effectiveness of the proposed method of correction in comparison with the previously considered methods, the established positive trend is being followed also at the 2nd and 3rd stages of the experiment, which indicates the effectiveness of this correction method.
 The most pronounced positive effect of normalizing the level of vascular growth factor is observed when using a hypoglycemic drug in combination with the administration of aflibercept, a solution of L-arginine and citicoline (in group No. 7).

English

Cisplatin (CP) is a highly efficient remedy in cancer treatment, but it adversely affects the testicular tissue. This work assessed the ameliorative efficacy of Lcarnitine (LC) against CP induced oxidative stress in rat testis, via investigating testosterone level and tissue oxidative/antioxidant parameters, histological alterations, and immunohistochemical expressions of intermediate filaments (IFs) proteins; vimentin (VIM) and cytokeratin 18 (CK18). Twenty-eight rats were assigned into four groups (7 rats each) as follows; groups I and II received saline and LC (100 mg/kg b.wt.) respectively orally once daily for 30 days; group III were injected with a single dose of CP (7.5 mg/kg, IP), 27 days after starting the experiment. Group IV received both LC and CP. Injection of CP significantly decreased serum testosterone and glutathione reductase and catalase in the testicular tissues and elevated malondialdehyde. Histologically, testes of the CP treated group revealed marked degenerative changes. Also, overexpression of both VIM and CK18 in testicular tissues were recorded. However, the administration of LC with CP restored the biochemical parameters, histological and immunohistochemical pictures towards the normalcy. Accordingly, LC is recommended as a supplement with chemotherapy to ameliorate its oxidative stress. This is the first study investigating the immunohistochemical expressions of IFs proteins, VIM and CK18, following administration of LC as a protective agent against CP induced testicular toxicity in rats

The role of lipid peroxidation in the pathogenesis of experimental diabetic retinopathy

The aim of work – to analysis of changes in the level of primary products of lipid peroxidation in experimental animals were simulated diabetic retinopathy and against the background of its correction.
 The obtained results indicate an increase in the content of lipid peroxidation, starting from the 30th and with further progression on the 60th and 180th days of experimental diabetic retinopathy, which is confirmed by an increase in the level of diene conjugates in the 2nd group, the maximum of which is observed at the 3rd stage. Correction with hypoglycemic agents in the 3rd group had a positive effect, but was not able to reduce the level of primary products of lipid peroxidation and restore antioxidant activity, so the use of additional agents became necessary. The use of aflibercept and a nitric oxide donor in the 4th group to correct the development of diabetic retinopathy significantly suppressed oxidative stress, the maximum of which occurred on the 180th day of the experiment, but did not reach control indicators. It was proven that the combined administration of bromfenac and aflibercept in the 5th group significantly reduced the number of primary LPO products, but not as significantly as in the 4th group. It was proved that the administration of aflibercept, L-carnitine and bromfenac to the animals of the 6th group reduced the content of diene conjugates already on the 30th and continued on the 60th and 180th days of the study, but it also did not reach the control indicators. The combination of metformin, aflibercept, L-arginine and citicoline in rats of the 7th group proved to be the most effective correction, as evidenced by the normalization of the level of the studied indicators on the 30th and 60th days of the experiment, and on the 180th, a decrease in the content of markers was detected oxidative stress to control indicators.

The effect of adding L-Carnitine to the GnRH-antagonist protocol on assisted reproductive technology outcome in women with polycystic ovarian syndrome: a randomized clinical trial

Objective This study aimed to investigate the effect of adding L-Carnitine to the gonadotropins on ART outcome in frozen-thawed embryo transfer cycles among PCOS women. Methods In this randomized clinical trial, 83 patients with PCOS were randomized to either L-Carnitine supplemented (n = 42) or control (n = 41) groups. The L-Carnitine group was given 3000 mg of oral L-Carnitine daily until the final day of ovulation. The numbers of metaphase II (MII) oocytes, 2-pronuclears (2PNs), oocyte maturity rate, fertilization rate, fertilization proportion as well as implantation, chemical and clinical pregnancy rates were compared between the two groups. Results Even though the duration of stimulation and endometrial thickness were comparable between groups (p > .05), serum estradiol level on the day of oocyte triggering, was significantly higher in the L-Carnitine group compared to the control group (p < .05). In contrast, the number of retrieved and MII oocytes as well as the number of 2PNs and obtained embryos were similar between groups (p > .05). Moreover, oocyte maturity rate (0.85 ± 0.38 vs. 1.02 ± 0.90), fertilization proportion (0.62 ± 0.44 vs. 0.80 ± 0.86), fertilization rate (0.70 ± 0.22 vs. 0.76 ± 0.19) along with implantation rate (18.1 vs. 13.7%), chemical (26.8 vs. 30.7%) and clinical (24.3 vs. 25.6%) pregnancy rates, were all comparable between L-Carnitine and control groups respectively (p > .05). Conclusions Our result showed that oral L-Carnitine administration during induction of ovulation among PCOS women could not improve laboratory and pregnancy outcome.

Potential Ameliorative Effects of L-Carnitine on Imidacloprid-Induced Hepato- and Nephrotoxicity in Male Albino Rats

The current study was intended to evaluate the possible protective role of L-Carnitine (LC) against imidacloprid (IM)-induced hepato- and nephrotoxicity in male albino rats. Thirty male albino rats were divided into 6 groups (n=5); control group, IM (32 mg/kg BW, 1/10 LD50)-treated group, LC200 (200 mg/kg BW)-treated group, LC400 (400 mg/kg BW)-treated group, IM+LC200-treated group, and IM+LC400-treated group. All treatments were given by oral route once daily for four weeks. Hematologically, the results exhibited that IM administration induced a significant decrease in red blood cells (RBCs) count, hemoglobin (Hb) and hematocrit (Ht) values. The erythrocytic indices (MCV, MCH and MCHC) displayed non-significant change in all treated groups. However, IM-treated group showed a significant leukocytosis and thrombocytosis after four weeks of treatment as compared to control group. Biochemically, the results revealed that IM convinced a significant elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) activities, as well as serum total bilirubin (TB), direct bilirubin (DB) and indirect bilirubin (IB), globulins, urea, creatinine, potassium (K+), pro-inflammatory cytokines (tumor necrosis factor- alpha and interleukin-6) levels at the end of experiment matching with the control group. However, IM administration resulted in a significant diminution in the serum of total proteins (TP), albumin, and sodium (Na+) levels, with a significant increase and decrease respectively in the levels of lipid peroxidation and antioxidant biomarker in the hepatic and renal tissues of rats after four weeks of treatments as compared to control group. Histopathologically, IM administration revealed marked degenerative and necrotic alterations in the liver and kidney. Conversely, LC treatment at two doses (200 and 400 mg) ameliorated IM-induced alterations in the blood picture, oxidative damage and inflammation in the liver and kidneys.Finally, it could be concluded that treatment with LC at two doses (200 and 400 mg) ameliorated IM-induced oxidative damage, alterations in the hematology, liver and kidney function tests, as well as their histopathology. However, administration of LC at a dose of 400 mg/kg BW showed better protective effects against IM-induced hepato-nephrotoxicity as compared to the low dose (200 mg/kg BW).

Carnitine status before and after paracentesis in patients with ascites and liver cirrhosis and improvement of subjective symptoms by intravenous administration of carnitine ― Initial study

Carnitine status before and after paracentesis in patients with ascites and liver cirrhosis and improvement of subjective symptoms by intravenous administration of carnitine ― Initial study

DYNAMICS OF THE MALONDIALDEHYDE LEVELS IN EXPERIMENTAL DIABETIC RETINOPATHY AND METHODS OF ITS CORRECTION

Diabetes is currently considered a non-infectious epidemic. At the same time the main reason for the development of blindness in developed countries are pathological changes in blood vessels in eye diseases, primarily in diabetic retinopathy. The purpose of the study: analysis of changes in secondary products of lipid peroxidation in experimental diabetic retinopathy and in different ways of its correction. The study was performed on white Wistar rats weighing 180-200 g. According to the tasks, the animals were divided into 7 groups. Type 2 diabetes mellitus and diabetic retinopathy were simulated by intraperitoneal administration of streptozotocin (Sigma, USA) dissolved in 0.1 M citrate buffer with a pH of 4.5. The dose of streptozotocin 55 mg / kg body weight was divided into two injections. The introduction of streptozotocin was preceded by a high-fat diet for 28 days. Corrective agents used in the study: metformin, aflibercept, L-carnitine, bromfenac, L-arginine and citicoline.&#x0D; The results obtained indicate an increase in the activity of lipid peroxidation, starting from the 30th and with subsequent progression to the sixtieth and one hundred and eightieth days of experimental diabetic retinopathy. This is confirmed by the increase in the level of malondialdehyde in the 2nd group, the maximum of which is observed at the third stage. Correction with hypoglycemic agents in the 3rd group had a positive effect, but was not able to reduce the level of secondary products of lipid peroxidation, so it became necessary to use additional agents. The use of aflibercept and a nitric oxide donor in the 4th group to correct the development of diabetic retinopathy significantly inhibited oxidative stress, the maximum of which occurred on the one hundred and eightieth day of the experiment, but did not reach the control values. It was proved that the combined administration of bromfenac and aflibercept in the 5th group significantly reduced the amount of LPO secondary products, but not as significantly as in the 4th group. It was proved that the administration of aflibercept, L-carnitine and bromfenac to animals of the 6th group reduced the content of LPO secondary products already on the 30th day and was prolonged on the 60th and 180th days of the study, but did not reach the control values ​​either.&#x0D; The most effective correction was the combination of metformin, aflibercept, L-arginine and citicoline in rats of the 7th group, as evidenced by the normalization of the level of malondialdehyde on the thirtieth and sixtieth days of the experiment, and on the one hundred and eightieth a decrease in the content of the marker to the control values ​​was recorded.

ПРЕНАТАЛЬНОЕ ПИТАНИЕ ДОМАШНЕЙ ПТИЦЫ И ЕГО ПОСТНАТАЛЬНЫЕ ЭФФЕКТЫ (обзор)

Fast growth rate in modern meat-type poultry is accompanied by several metabolic disorders resulting from the discrepancy between embryonic and postembryonic growth and development. Prenatal period of avian ontogenesis is characterized by abrupt physiologic and metabolic alterations and hence any disturbance at this stage can affect the hatch efficiency and subsequent postnatal growth and productivity (E.T. Moran, 2007; V.L. Christensen et al., 2004). The embryonic development in eggs can be supported by the in ovo nutrition using natural nutrients (amino acids, carbohydrates, vitamins) as well as growth stimulators and hormones; this approach can also prepare the poults for the intense postnatal growth (P.R. Ferket, 2016). From the nutrigenomic point of view, the nutrients and bioactive substances can affect gene expression (V.I. Fisinin et al., 2006; L. Bordoni et al., 2019). The experiments with the in ovo nutrition proved that the injections of nutrients can affect physiological status of broiler embryos and hatched broiler chicks. E.g. the injections of carbohydrates enlarge the pool of energy available for the embryo and decreases the catabolism of proteins and lipids during the final stage of incubation, resulting in the increases in the weight of the hatched chicks and in postnatal growth rate, supported by better development of the gastrointestinal tract (R. Kornasio et al., 2011; R. Jhaet al., 2019). All amino acids are necessary for the developing embryo; the absence of any of the amino acids can disrupt protein synthesis and homeostasis in the embryo, resulting in poorer postnatal growth and development. A bulk of studies were published which demonstrated the positive effects of the in ovo injections of individual or mixed amino acids on postnatal growth rate (Y. Ohta et al., 2001; T.M. Shafey et al., 2014; L.L. Yu et al., 2018). Ca. 94 % of total metabolizable energy in the embryo is generated via the oxidation of fatty acids. These oxidative processes, in turn, generate substantial amounts of free radicals which can result in vast cellular damage (P. Surai and V.I. Fisinin, 2013; A. Yigit et al., 2014). The administration of vitamins with antioxidative activity (like С or E) during the embryonic period positively affected the postnatal development of the immune system in chicks (S.A. Selim et al., 2012; S. Nowaczewski et al., 2012). The administration of L-carnitine into the embryos was shown to enhance pre-hatch glucose utilization in the anaerobic conditions and postnatal growth in the chicks (T.M. Shafey et al., 2010; A.M. Dolgorukova, 2017). The in ovo nutrition can therefore be an instrument of significant improvement of the hatchability of the injected eggs and subsequent growth efficiency in hatched chicks, resulting in explicit economic effect (E.D. Peebles, 2018). It should, however, be noted that this technique has not still found application in the commercial poultry production and that for wider knowledge on the stimulating effects of different nutrients on the development of avian embryo further research is required.

PRENATAL NUTRITION OF POULTRY AND ITS POSTNATAL EFFECTS (review)

Fast growth rate in modern meat-type poultry is accompanied by several metabolic disorders resulting from the discrepancy between embryonic and postembryonic growth and development. Prenatal period of avian ontogenesis is characterized by abrupt physiologic and metabolic alterations and hence any disturbance at this stage can affect the hatch efficiency and subsequent postnatal growth and productivity (E.T. Moran, 2007; V.L. Christensen et al., 2004). The embryonic development in eggs can be supported by the in ovo nutrition using natural nutrients (amino acids, carbohydrates, vitamins) as well as growth stimulators and hormones; this approach can also prepare the poults for the intense postnatal growth (P.R. Ferket, 2016). From the nutrigenomic point of view, the nutrients and bioactive substances can affect gene expression (V.I. Fisinin et al., 2006; L. Bordoni et al., 2019). The experiments with the in ovo nutrition proved that the injections of nutrients can affect physiological status of broiler embryos and hatched broiler chicks. E.g. the injections of carbohydrates enlarge the pool of energy available for the embryo and decreases the catabolism of proteins and lipids during the final stage of incubation, resulting in the increases in the weight of the hatched chicks and in postnatal growth rate, supported by better development of the gastrointestinal tract (R. Kornasio et al., 2011; R. Jhaet al., 2019). All amino acids are necessary for the developing embryo; the absence of any of the amino acids can disrupt protein synthesis and homeostasis in the embryo, resulting in poorer postnatal growth and development. A bulk of studies were published which demonstrated the positive effects of the in ovo injections of individual or mixed amino acids on postnatal growth rate (Y. Ohta et al., 2001; T.M. Shafey et al., 2014; L.L. Yu et al., 2018). Ca. 94 % of total metabolizable energy in the embryo is generated via the oxidation of fatty acids. These oxidative processes, in turn, generate substantial amounts of free radicals which can result in vast cellular damage (P. Surai and V.I. Fisinin, 2013; A. Yigit et al., 2014). The administration of vitamins with antioxidative activity (like С or E) during the embryonic period positively affected the postnatal development of the immune system in chicks (S.A. Selim et al., 2012; S. Nowaczewski et al., 2012). The administration of L-carnitine into the embryos was shown to enhance pre-hatch glucose utilization in the anaerobic conditions and postnatal growth in the chicks (T.M. Shafey et al., 2010; A.M. Dolgorukova, 2017). The in ovo nutrition can therefore be an instrument of significant improvement of the hatchability of the injected eggs and subsequent growth efficiency in hatched chicks, resulting in explicit economic effect (E.D. Peebles, 2018). It should, however, be noted that this technique has not still found application in the commercial poultry production and that for wider knowledge on the stimulating effects of different nutrients on the development of avian embryo further research is required.

Neuroprotective Effect of L-carnitine. Focus on Changing Mitochondrial Function

Introduction: In this study, the neuroprotective effect of L-carnitine administered per os in a dose of 25 mg/kg – 800 mg/kg was evaluated. The effects of L-carnitine on changes in mitochondrial function were also studied.&#x0D; Materials and Methods: The neuroprotective effect and mitochondrial function were evaluated in a model of perma­nent focal ischemia in Wistar-line rats. L-carnitine was administered to rats orally for 72 hours from the moment of modeling ischemia. On the 4th day after the ischemia simulation, the change in the respiratory function of the mito­chondria, the opening time of the mitochondrial permeability transition pore, the mitochondrial membrane potential, the concentration of intracellular calcium and the size of the cerebral necrosis zone were determined in rats’ brain supernatant.&#x0D; Results: As a result, it was found that the administration of L-carnitine contributed to the restoration of mitochondrial function and a decrease in the size of the brain necrosis zone. At the same time, the administration of L-carnitine in low doses (25 mg/kg – 100 mg/kg) did not have a significant effect on the change in the concentration of intracellular calcium. It should be noted that an increase in the dose of L-carnitine from 200 mg/kg to 800 mg/kg was not accom­panied by a significant increase in the therapeutic effect.&#x0D; Discussion: L-carnitine is one of the key biomolecules that directly affect metabolic processes. It is known that L-car­nitine acts as a ”shuttle” for long-chain fatty acids and thus can affect the alteration of mitochondrial function. Howev­er, the detailed nature of the mitochondriotropic action of L-carnitine has not been yet established. This was the focus of this study, which showed that the mitochondrion-oriented effect of L-carnitine is dose-dependent and expressed in the form of restoring the respiratory function of mitochondria, restoring the mitochondrial potential and increasing the latent opening time of the mitochondrial permeability transition pore, reducing the level of intracellular calcium.&#x0D; Conclusion: The study allowed us to expand our understanding of the L-carnitine neuroprotective effect and the effect of this compound on changes in mitochondrial function.&#x0D; Graphical abstract:

L-carnitine exerts a nutrigenomic effect via direct modulation of nuclear receptor signaling in adipocytes, hepatocytes and SKMC, demonstrating its nutritional impact

L-carnitine is an indispensable metabolite facilitating the transport of fatty acids into the mitochondrial matrix and has been previously postulated to exert a nutrigenomic effect. However, the underlying molecular mechanisms remain mostly unclear. We hypothesized that L-carnitine interacts with nuclear receptors involved in metabolic regulation, thereby modulating downstream targets of cellular metabolism. Therefore, we investigated the effect of L-carnitine supplementation on protein activity, mRNA expression, and binding affinities of nuclear receptors as well as mRNA expression of downstream targets in skeletal muscle cells, hepatocytes, and differentiated adipocytes. L-carnitine supplementation to hepatocytes increased the protein activity of multiple nuclear receptors (RAR, RXR, VDR, PPAR, HNF4, ER, LXR). Diverging effects on the mRNA expression of PPAR-α, PPAR-δ, PPAR-γ, RAR-β, LXR-α, and RXR-α were observed in adipocytes, hepatocytes, and skeletal muscle cells. mRNA levels of PPAR-α, a key regulator of lipolysis and β-oxidation, were significantly upregulated, emphasizing a role of L-carnitine as a promoter of lipid catabolism. L-carnitine administration to hepatocytes modulated the transcription of key nuclear receptor target genes, including ALDH1A1, a promoter of adipogenesis, and OGT, a contributor to insulin resistance. Electrophoretic mobility shift assays proved L-carnitine to increase binding affinities of nuclear receptors to their promoter target sequences, suggesting a molecular mechanism for the observed transcriptional modulation. Overall, these findings indicate that L-carnitine modulates the activity and expression of nuclear receptors, thereby promoting lipolytic gene expression and decreasing transcription of target genes linked to adipogenesis and insulin resistance.

L-carnitine administration effects on AMPK, APPL1 and PPAR? genes expression in the liver and serum adiponectin levels and HOMA-IR in type 2 diabetes rat model induced by STZ and nicotinamide

L-carnitine administration effects on AMPK, APPL1 and PPAR? genes expression in the liver and serum adiponectin levels and HOMA-IR in type 2 diabetes rat model induced by STZ and nicotinamide

Rats with congenital hydronephrosis show increased susceptibility to renal ischemia-reperfusion injury.

Many drug candidates have shown significant renoprotective effects in preclinical models; however, there is no clinically used effective pharmacotherapy for acute kidney injury. The failure to translate from bench to bedside could be due to misleading results from experimental animals with undetected congenital kidney defects. This study was performed to assess the effects of congenital hydronephrosis on the functional capacity of tubular renal transporters as well as kidney sensitivity to ischemia‐reperfusion (I‐R)‐induced injury in male Wistar rats. Ultrasonography was used to distinguish healthy control rats from rats with hydronephrosis. L‐carnitine or furosemide was administered, and serial blood samples were collected and analyzed to assess the effects of hydronephrosis on the pharmacokinetic parameters. Renal injury was induced by clamping the renal pedicles of both kidneys for 30 min with subsequent 24 hr reperfusion. The prevalence of hydronephrosis reached ~30%. The plasma concentrations after administration of L‐carnitine or furosemide were similar in both groups. I‐R induced more pronounced renal injury in the hydronephrotic rats than the control rats, which was evident by a significantly higher kidney injury molecule‐1 concentration and lower creatinine concentration in the urine of the hydronephrotic rats than the control rats. After I‐R, the gene expression levels of renal injury markers were significantly higher in the hydronephrotic kidneys than in the kidneys of control group animals. In conclusion, our results demonstrate that hydronephrotic kidneys are more susceptible to I‐R‐induced damage than healthy kidneys. Unilateral hydronephrosis does not affect the pharmacokinetics of substances secreted or absorbed in the renal tubules.

L-carnitine as primary or adjuvant treatment in infertile patients with varicocele. A systematic review.

Varicocele has been found to impair the function of the epididymis resulting in subfertility whereas the varicocelectomy can resolve the phenomenon. L-carnitine is regarded as a biomarker for the function of the epididymis and has been found in reduced concentrations in infertile patients of various causes, including infertile men with varicocele. It seems that Lcarnitine and varicocele share clinical significance and the area of research looks promising. To identify the role of L-carnitine in the treatment of varicocele. A systematic search was performed in Pubmed/Medline with the terms (L-carnitine) and (varicocele) and (L-carnitine) and (varicocelectomy). Inclusion criteria were studies reported outcomes of L-carnitine administration alone or in duet, as primary or adjuvant treatment to varicocele. Exclusion criteria were non-English language and animal studies. Studies using L-carnitine as part of a panel of therapeutic agents were avoided. Only four suitable studies were identified for discussion. In one randomized study, the combination of L-carnitine and cinnoxicam improved semen parameters in patients with non-high-grade varicocele compared to L-carnitine alone and had a favourable effect on pregnancy rates but the effect of grade is unknown. In another study, as an adjuvant treatment to varicocelectomy, L-carnitine showed no clear benefit. Finally, in comparison to surgery, the results are inconclusive; two studies showed some benefit might be expected in low-grade or subclinical varicocele, but surgery appears superior. The evidence regarding the role of L-carnitine as a primary or adjuvant treatment of varicocele is sparse. The pathophysiological significance of L-carnitine implicates a potential role of the molecule in the management of varicocele, but the evidence so far is controversial for any recommendations. L-carnitine might be taken into consideration in selected cases; however, further search is needed in order the optimal role of L-carnitine in infertile patients with varicocele to be clarified.

L-Carnitine Mitigates Oxidative Stress and Disorganization of Cytoskeleton Intermediate Filaments in Cisplatin-Induced Hepato-Renal Toxicity in Rats.

Cisplatin (CP) is one of the most active medications in cancer treatment and has some adverse effects such as hepatotoxicity and nephrotoxicity. The present research was planned to determine the protective effects of L-carnitine (LC) against CP-induced hepato-renal oxidative stress in rats, via investigating of some serum biochemical and tissue oxidative/antioxidant parameters, histological alterations, and immunohistochemical expressions of two different intermediate filaments (IFs) proteins; vimentin (VIM) and cytokeratin 18 (CK18). Twenty-eight rats were divided into four groups (7 rats each). Groups I and II were orally administered saline and LC (100 mg/kg body weight), respectively, once daily for 30 consecutive days. Group III received saline orally once daily and a single dose of CP on the 27th day of the experiment [7.5 mg/kg, intraperitoneal (IP)]. Group IV received both LC and CP. Injection of CP significantly (P ≤ 0.05) increased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities and creatinine and urea levels, while serum total protein, albumin, and globulin concentrations significantly (P ≤ 0.05) decreased. In addition, CP induced a dramatic increase in the Malondialdehyde (MDA) level along with a substantial decrease in reduced glutathione (GSH) and catalase (CAT) in the hepato-renal tissues. Histologically, both liver and kidney of the CP treated group revealed marked degenerative changes. Moreover, overexpression of both VIM and CK18 in hepato-renal tissues were noted after CP injection. On the other hand, the administration of LC in the CP injected group (Group IV) restored the biochemical parameters, histological, and immunohistochemical pictures toward the normalcy. In conclusion, LC may be supplemented for chemotherapy with CP to ameliorate its oxidative stress and restore the normal organization of IFs, especially VIM and CK18 within the CP intoxicated hepato-renal cells.

L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction.

Background/AimsAccumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro.MethodsSprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC.ResultsLC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells.ConclusionsLC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

Effect of levocarnitine administration in patients with chronic liver disease.

L-carnitine administration was reported to improve sarcopenia in patients with cirrhosis. However, the amount of evidence from previous studies is not sufficient. The present study aimed to clarify the effect of levocarnitine (L-carnitine) administration on body composition in patients with chronic liver disease (CLD). In the present study, 85 patients with L-carnitine administration and 87 control patients were enrolled and divided them into two groups, the L-carnitine administration group (LAG, n=44) and the without L-carnitine administration (controls, n=44) group, by using propensity score matching for age, sex, body mass index (BMI) and serum albumin. Δ skeletal muscle mass index (SMI)/year, Δ intramuscular adipose tissue content (IMAC)/year and Δ bone mineral density (BMD)/year were examined during L-carnitine administration. Each parameter was measured by computed tomography (CT) or dual-energy X-ray absorptiometry. The median age overall was 69 years (IQR, 64.0, 75.0); 36 were men and 52 were women. The median SMI was 37.4 cm2/m2 (IQR, 34.01, 44.34). The initial CT scans showed similar median values of SMI for the two groups [37.74 (34.17, 43.58) and 37.16 (33.83, 44.34), P=0.67]. However, the median ΔSMI/year for the LAG and controls were 0.95% (-3.07, 6.10) and -2.34% (-5.34, 0.53), respectively (P=0.003). The median Δ whole body BMD/year for the LAG and controls were -0.24% (-1.20, 0.91) and -1.04% (-2.16, 0.47), respectively (P=0.038). The median ΔIMAC/year and Δ lumbar spine BMD were not significantly different between the LAG and controls. L-carnitine administration may prevent the loss of skeletal muscle mass and BMD; therefore, it may be used as a new treatment option for osteoporosis and sarcopenia in patients with CLD.

The effects of L-carnitine supplementation on indicators of inflammation and oxidative stress: a systematic review and meta-analysis of randomized controlled trials.

Several trials investigated the efficacy of L-carnitine administration on markers of inflammation and indicators of oxidative stress; however, their findings are controversial. The aim of this study was to conduct a comprehensive meta-analysis and a critical review, which would analyze all randomized controlled trials (RCTs) in order to determine the effects of L-carnitine supplementation on inflammatory markers and oxidative stress. An electronic search was performed using Scopus, Cochrane Library, PubMed, Google scholar and Web of Science databases on publications from 1990 up to May 2020. Human RCTs conducted in healthy subjects or participants with certain disorders which investigating the efficacy of L-carnitine supplementation compared to control (placebo, usual treatment or no intervention) on inflammation and oxidative markers were included. Data were pooled applying a random-effects model and as the overall effect size, weighted mean difference (WMD) was presented. Between heterogeneity among studies was computed using Cochran's Q test and I-square (I2). Quality of studies assessed using the Jadad scale. Dose-response analysis was measured using meta-regression. The funnel plot, as well as the Egger's regression test was applied to determine the publication bias. 44 trials (reported 49 effect sizes for different outcomes of interest) met the inclusion criteria for this meta-analysis. According to the findings, L-carnitine supplementation resulted in a significant reduction in C-reactive protein (CRP) (WMD: -0.10; 95% CI: -0.14, -0.06), interleukin 6 (IL-6) (WMD: -1.87; 95% CI: -2.80, -0.95), tumor necrosis factor-α (TNF-α) levels (WMD: -1.43; 95% CI: -2.03, -0.84), and malondialdehyde (MDA) (WMD: -0.47; 95% CI: -0.76, -0.18) levels, while there was a significant increase in superoxide dismutase (SOD) (WMD: 2.14; 95% CI: 1.02, 3.25). However, no significant effects of L-carnitine on glutathione peroxidase (GPx) (WMD: 0.02; 95% CI: -0.01, 0.05) and total antioxidant capacity (TAC) (WMD: 0.14; 95% CI: -0.05, 0.33) were found. L-carnitine supplementation was associated with lowering of CRP, IL-6, TNF-α, and MDA, and increasing SOD levels, but did not affect other inflammatory and oxidative stress biomarkers.

L-carnitine reduces hospital admissions in patients with hepatic encephalopathy.

The aim of this study was to determine whether oral L-carnitine administration reduces the blood ammonia concentration and number of hospital admissions for hepatic encephalopathy in patients with advanced cirrhosis. Of 68 patients with hepatic encephalopathy treated with oral L-carnitine supplementation from April 2013 to March 2016, we enrolled 19 patients who had received full standard treatment. We analyzed blood ammonia concentration, number of hospital admissions, and prognosis to determine how effective L-carnitine was in achieving mid-term to long-term suppression of recurrent hepatic encephalopathy. Median blood ammonia concentrations at the start, 1 week, 12 weeks, 24 weeks, and 48 weeks were 159, 79, 75, and 82 μg/dL, respectively. Blood ammonia concentrations 12 week, 24 weeks, and 48 weeks after L-carnitine administration were significantly lower than those at the start (P < 0.0001, respectively). During the 3 years prior to oral L-carnitine administration, the enrolled patients were hospitalized a total of 29 times for hepatic encephalopathy. However, during the 3 years following oral L-carnitine administration, they were admitted a total of six times for hepatic encephalopathy (P < 0.001). Median survival time was 40.9 months. Child-Pugh scores before and after oral L-carnitine administration differed significantly, whereas liver reserve function, nutritional status, and muscle index did not change significantly. Oral L-carnitine administration is effective and free of adverse effects in patients with hyperammonemia and reduces the number of hospital admissions for hepatic encephalopathy.

Impaired brain function improved by l-carnitine in patients with cirrhosis: evaluation using near-infrared spectroscopy

To evaluate the effects of l-carnitine on impaired brain function in patients with liver cirrhosis. We conducted a retrospective cohort study that included sequential 80 liver cirrhosis patients with impaired brain function evaluated using near-infrared spectroscopy (NIRS). Among them, l-carnitine was administered to 48 patients. The NIRS data and blood ammonia level at baseline and after 8 weeks of treatment were compared between patients administered with l-carnitine (l-carnitine group) and those who were not (control group). The NIRS data at baseline were similar between the l-carnitine and control groups (0.04 ± 0.04 vs. 0.04 ± 0.05 mMmm, p = n.s), whereas those in the l-carnitine group (n = 48) were significantly better than that of the control group at 8 weeks of treatment (n = 32) (0.103 ± 0.081 vs. 0.040 ± 0.048 mMmm, p < 0.001). In the l-carnitine group, 35.4% (17/48) of patients had hyperammonemia. The NIRS data of the l-carnitine group at 8 weeks of treatment were significantly improved than that of the control group, irrespective of baseline ammonia levels (0.11 ± 0.09 vs. 0.04 ± 0.05 mMmm, p = 0.005, and 0.10 ± 0.06 vs. 0.02 ± 0.03 mMmm, p = 0.003, for normal baseline ammonia and elevated ammonia levels, respectively). In the multivariate analysis, l-carnitine administration (odds ratio [OR] 3.51, 95% confidence interval [CI] 1.23–9.99, p = 0.019) and baseline NIRS data of ≤ 0.07 mMmm (OR 5.21, 95% CI 1.69–16.0, p = 0.0041) were found as independent significant factors. l-carnitine improves impaired brain function in patients with liver cirrhosis.