Animals ; Apoptosis/drug effects* ; Autophagy/drug effects* ; Carnitine/pharmacology* ; Cells, Cultured ; Endothelial Cells ; Lipopolysaccharides ; Mice

OBJECTIVETo investigate the protective effect of L-carnitine on the testis and epididymis against ornidazole (ORN)-induced injury in male rats.

METHODSForty male SD rats weighing 200 -230 g were randomly divided into 5 groups, Group A treated with 0.5% sodium carboxymethyl cellulose, and Groups B, C, D and E with ORN at the daily dose of 400 mg/kg, 800 mg/kg, 400 mg/kg plus LC 100 mg/kg and 800 mg/kg plus LC 100 mg/kg, respectively, all by oral gavage for 20 days continuously. Twenty-four hours after the last administration, all the rats were put to death, their testes and epididymides harvested, weighed and subjected to HE staining. The indexes of the testes and epididymides were obtained and their histopathological changes observed.

RESULTSCompared with Group A, Groups B and C showed significant decreases in the indexes of the testis and epididymis (P < 0.05 and P < 0.01), while Group D exhibited no difference and Group E extremely significant difference (P < 0.01). HE staining revealed that the spermatogenic cells at all levels of testicular seminiferous tubules were neatly arranged in Group B, caduceus in some seminiferous tubules, with decreased number of sperm and sporadic spermatogenic cells in the epididymal duct. Necrotic and caduceus spermatogenic cells were observed in the seminiferous tubules of Group C, with significantly decreased number of sperm and lots of non-sperm cell components in the epididymal duct. No obvious changes were found in the testicular seminiferous tubules, nor evident reduction in the number of sperm in the epididymal duct of Group D. Group E showed decreased number of sperm in the testicular seminiferous tubules, necrotic and caduceus spermatogenic cells, obviously reduced number of sperm and a lot of non-sperm cell components in the epididymal duct.

CONCLUSIONORC can induce histopathological changes in the testis and epididymis of male rats, and L-carnitine plays a role in protecting the testis and epididymis from ORN-induced injury in male rats.

Animals ; Carnitine ; pharmacology ; Epididymis ; drug effects ; pathology ; Male ; Ornidazole ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Testis ; drug effects ; pathology

Animals ; Carnitine ; pharmacology ; H(+)-K(+)-Exchanging ATPase ; metabolism ; Mitochondria, Muscle ; enzymology ; Muscle, Skeletal ; drug effects ; Physical Conditioning, Animal ; Rats

OBJECTIVETo investigate the effect of exogenous carnitine on function of respiratory chain and antioxidant capacity in mitochondria of myocardium in rats.

METHODSForty male Wistar rats were randomized to 4 groups (n = 10): static control (C), supplementation of carnitine (LC), exercise-training (T) and training with supplementation of carnitine (TLC). LC and TLC animals were perfused carnitine by the dose of 300 mg/kg bw x d. T and TLC animals were forced to performed 6-week treadmill training. Heart were prepared immediately after exhaustive running. Myocardium mitochondria was extracted by differential centrifugation. Spectrophotometric analysis was used to evaluate activities of respiratory chain complex (C) I -IV and superoxide dismutase (SOD), malondialdehyde (MDA) level in myocardium mitochondria.

RESULTSTo compare with C group, C I and C IV activity in LC, T and TLC group were increased significantly (P < 0.05, P < 0.01), CII and C III activity in T and TLC group were increased significantly (P < 0.05, P < 0.01); to compare with LC group, C I - IV activity in TLC group were increased significantly (P < 0.05, P < 0.01); to compare with T group, CI and C IV activity in TLC group increased significantly (P < 0.05). To compare with C group, SOD activity increased remarkably, MDA was remarkably lower (P < 0.05, P < 0.01) in LC, T and TLC group; To compare with LC and T group, SOD activity increased remarkably, MDA was remarkably lower (P < 0.05) in TLC group.

CONCLUSIONCarnitine and training could improve function of respiratory chain and increased antioxidant capacity in myocardium mitochondria, there was better function of cooperation between carnitine and training.

Animals ; Antioxidants ; metabolism ; Carnitine ; pharmacology ; Electron Transport ; Male ; Malondialdehyde ; metabolism ; Mitochondria, Heart ; drug effects ; metabolism ; physiology ; Physical Conditioning, Animal ; physiology ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism

OBJECTIVETo evaluate the effect and safety of L-carnitine in the treatment of idiopathic oligoasthenozoospermia based on current clinical evidence.

METHODSWe searched the Cochrane Library, PubMed, MEDLINE, EMBASE, CNKI, VIP, CBM and Wanfang Database from the establishment to April 2014 for the published literature on the treatment of idiopathic oligoasthenozoospermia with L-carnitine. We conducted literature screening, data extraction, and assessment of the methodological quality of the included trials according to the inclusion and exclusion criteria, followed by statistical analysis with the RevMan 5. 2 software.

RESULTSSeven randomized controlled trials involving 751 patients with idiopathic oligoasthenozoospermia met the inclusion criteria, and 678 of them were included in the meta-analysis. L-carnitine treatment achieved a significantly increased rate of spontaneous pregnancy as compared with the control group (RR = 3.2, 95% CI 1.74 to 5.87, P = 0.0002). After 12-16 and 24-26 weeks of medication, total sperm motility (WMD = 5.21, 95% CI 2.78 to 7.64, P < 0.0001 and WMD = 9.29, 95% CI 1.28 to 17.29, P = 0.02) and the percentage of progressively motile sperm (WMD = 12.44, 95% CI 4.58 to 20.31, P = 0.002 and WMD = 9.76, 95% CI 3.56 to 15.97, P = 0.002) were remarkably higher than those in the control group, but no statistically significant differences were observed in sperm concentration between the two groups (WMD = 4.91, 95% CI -2.63 to 12.45, P = 0.2 and WMD = 0.93, 95% CI -3.48 to 5.34, P = 0.68). After 12-16 weeks of treatment, the percentage of morphologically abnormal sperm was markedly decreased in the L-carnitine group as compared with the control (WMD = -2.48, 95% CI -4.35 to -0.61, P = 0.009), but showed no significant difference from the latter group after 24-26 weeks (WMD = -4.38, 95% CI -9.66 to 0.89, P = 0.1). No statistically significant difference was found in the semen volume between the two groups after 12-16 or 24-26 weeks of medication (WMD = -0.13, 95% CI -0.43 to 0.18, P = 0.42 and WMD = 0.28, 95% CI -0.02 to 0.58, P = 0.07). No serious L-carnitine-related adverse events were reported in 4 of the randomniized controlled trials.

CONCLUSIONThe current evidence indicates that L-carnitine can improve spontaneous pregnancy and semen parameters in the treatment of idiopathic oligoasthenozoospermia, with no serious adverse reactions.

Asthenozoospermia ; drug therapy ; Carnitine ; adverse effects ; pharmacology ; Female ; Humans ; Male ; Pregnancy ; Pregnancy Rate ; Randomized Controlled Trials as Topic ; Semen Analysis ; Sperm Count ; Sperm Motility

OBJECTIVETo evaluate the effects of valsartan and carnitine on cardiomyocyte Calpain-1 and Bcl-xl expressions of dogs with chronic alcohol intake-induced cardiomyopathy.

METHODSDogs were randomly assigned into 4 groups (n = 7 each): (1) alcohol fed (free access to 5%, 1(st) week; 10% 2(nd) week; 500 ml 25% bolus plus free access to 5% from 3 to 24 weeks, A); (2) alcohol + valsartan (5 mg×kg(-1)×d(-1), B); (3) alcohol + carnitine (300 mg×kg(-1)×d(-1), C); (4) Control (D). After six months, all animals were assessed for left ventricular (LV) function by echocardiography. The Bad and Bcl-xl protein expressions were evaluated by immunohistochemistry. The expression of Calpain-1 protein was determined with Western blot. Myocardial morphology was quantified on HE stained slices and under electron microscopy. The terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) was performed for apoptosis analysis.

RESULTSCompared with group D, LVEDD and LVESD were significantly increased while EF and FS significantly decreased in group A. In alcohol fed group, expressions of Bad and Calpain-1 protein were significantly increased while Bcl-xl protein expression was downregulated, all changes could be significantly attenuated by intervention with valsartan and carnitine (all P < 0.05).

CONCLUSIONThese data suggest that alcohol could promote cardiac myocyte apoptosis, reduce cardiac function and aggravate myocardial remodeling which valsartan and carnitine could reduce alcoholic cardiomyopathy by downregulating Calpain-1 and Bad protein expression and upregulating expression of Bcl-xl protein.

Animals ; Apoptosis ; drug effects ; Calpain ; metabolism ; Cardiomyopathy, Alcoholic ; metabolism ; pathology ; Carnitine ; pharmacology ; Disease Models, Animal ; Dogs ; Myocytes, Cardiac ; drug effects ; metabolism ; Tetrazoles ; pharmacology ; Valine ; analogs & derivatives ; pharmacology ; Valsartan ; bcl-Associated Death Protein ; metabolism ; bcl-X Protein ; metabolism

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.
Animals ; Burns ; Carnitine/pharmacology* ; Caspase 1/pharmacology* ; Dimethyl Sulfoxide/pharmacology* ; Endoplasmic Reticulum Stress ; Female ; Humans ; Liver ; NLR Family, Pyrin Domain-Containing 3 Protein ; Pyroptosis ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effects of L-carnitine (LC) on the apoptosis of spermatogenic cells and on the count and motility of epididymal sperm in rats with diabetes mellitus (DM).

METHODSTwenty-four SD rats (200-230 g) were randomly divided into a control group, a DM model group and an LC group. After the establishment of DM models in the latter two groups by injection of streptozotocin (STZ) at 65 mg/kg, the controls and DM models were treated intragastrically with physiological saline, while the rats in the LC group with LC at 300 mg/kg, all for 6 consecutive weeks. Twenty-four hours after the last administration, all the rats were killed for the detection of the count and motility of epididymal sperm and the apoptosis of spermatogenic cells.

RESULTSThe motilities of caput and cauda epididymal sperm were (53.7 +/- 1.8)% and (60.3 +/- 1.6)% in the LC group, significantly higher than in the DM model group ([32.2 +/- 2.0]% and [40.5 +/- 1.4]%, P < 0.05), but remarkably lower than in the control ([63.1 +/- 2.4 ]% and [68.9 +/- 1.3]%, P < 0.05). The count of cauda epididymal sperm was (25.5 +/- 1.1) x 10(6)/100 mg in the DM models, and was increased to (32.0 +/- 1.5) x 10(6)/100 mg after LC treatment (P < 0.05), but still markedly lower than in the controls ([37.8 +/- 1.1] x 10(6)/100 mg) (P < 0.05). The apoptosis rate of spermatogenic cells was (52.5 +/- 4.4)% in the DM model group, and it was reduced to (35.3 +/- 3.5)% after LC administration (P < 0.05), but still significantly higher than in the control group ([3.7 +/- 1.3]%) (P < 0.05).

CONCLUSIONIntragastrically gavage of LC at 300 mg/kg for 6 weeks increased the epididymal sperm count, improved sperm motility, and reduced the apoptosis of spermatogenic cells in rats with DM.

Animals ; Apoptosis ; drug effects ; Carnitine ; pharmacology ; Diabetes Mellitus, Experimental ; physiopathology ; Epididymis ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sperm Count ; Sperm Motility ; drug effects ; Spermatogenesis ; drug effects ; Spermatozoa ; drug effects

OBJECTIVETo investigate the effects of carnitine on human sperm motility and its potential role in the treatment of male infertility diseases.

METHODSWe obtained sperm by testis puncture from obstructive azoospermia patients and cultured them in vitro with normal culture solution (the control group) and the solution with L-carnitine at the concentration of 100 and 250 mmol/L, respectively. We observed the changes in sperm motility and morphology before and after the treatment, detected the expressions of the germ-specific genes, Vasa, Dazl, Acr, Prm1 and ATPase 6.0 by RT-PCR, and investigated the relationship between L-carnitine and the genes associated with sperm development and maturation.

RESULTSAfter 24 -72 hours of treatment, the percentage of motile sperm was significantly higher in the 100 mmol/L L-carnitine group than in the control and 250 mmol/L L-carnitine groups (P < 0.01); the number of forward moving sperm was obviously increased and sperm morphology remained normal in the 100 mmol/L L-carnitine group. RT-PCR showed that L-carnitine increased the expressions of Acr, Prm1, Dazl and ATPase 6. 0 at the concentration of 100 mmol/L, and decreased the expressions of Dazl, Acr and Prm1 at 250 mmol/L.

CONCLUSIONL-carnitine at a proper concentration may improve the motility of incubated testicular sperm by upregulating the expressions of some sperm-specific genes, which helps sperm selection for intracytoplasmic sperm injection. However, a higher concentration of L-carnitine may reduce the expressions of these genes, probably due to its increased toxicity.

Azoospermia ; etiology ; genetics ; metabolism ; Carnitine ; pharmacology ; Cells, Cultured ; Gene Expression ; Humans ; Infertility, Male ; Male ; Reverse Transcriptase Polymerase Chain Reaction ; Sperm Count ; Spermatozoa ; drug effects ; metabolism ; Testis ; drug effects ; metabolism

The aim of the present study was to investigate the effect of carnitine on function of respiratory chain and metabolism of oxygen radical in mitochondria of skeletal muscle after exhaustive running in training rats. Forty male Wistar rats were randomly divided into 4 groups (n = 10): control, carnitine, training and training + carnitine groups. The training and training + carnitine groups received 6-week treadmill training, whereas carnitine and training + carnitine groups were administered intragastrically with carnitine (300 mg/kg per day, 6 d/week) for 6 weeks. After exhaustive running, all the rats from 4 groups were sacrificed to obtain quadriceps muscles samples, and muscle mitochondria were extracted by differential centrifugation. Spectrophotometric analysis was used to evaluate activities of respiratory chain complexes (RCC) I-IV, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) in the skeletal muscle mitochondria. The results showed that, compared with the control group, the carnitine group exhibited increased RCCI and RCCIII activities (P < 0.05), the training + carnitine group exhibited increased RCCI, RCCIII and RCCIV activities (P < 0.05 or 0.01). Moreover, RCCIII activity in the training + carnitine group was higher than that in training group (P < 0.05). Compared with the control group, the carnitine, training and training + carnitine groups showed increased SOD activities ( P < 0.01), the carnitine and training + carnitine groups showed increased GSH-Px activities ( P < 0.01), the carnitine, training and training + carnitine groups showed increased MDA contents (P < 0.05 or 0.01). The SOD and GSH-Px activities in training + carnitine group were higher than those in training group (P < 0.01), and the MDA level in the training + carnitine group was higher than that in the carnitine and training groups (P < 0.01). These results suggest that training and carnitine can increase function of respiratory chain, antioxidation and lipid peroxidation tolerance capacity in skeletal muscle mitochondria, and the improving effects of training and carnitine are synergistic.
Animals ; Antioxidants ; metabolism ; Carnitine ; pharmacology ; Electron Transport ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mitochondria, Muscle ; drug effects ; physiology ; Muscle, Skeletal ; drug effects ; physiology ; Physical Conditioning, Animal ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Running ; Superoxide Dismutase ; metabolism