Protective Role Of L-carnitine Research Articles

Protective Role of L-Carnitine against Methotrexate-Induced Side Effects on Submandibular Gland in Adult Male Albino Rats

Protective Role of L-Carnitine against Methotrexate-Induced Side Effects on Submandibular Gland in Adult Male Albino Rats

The protective role of l-carnitine on oxidative stress, neurotransmitter perturbations, astrogliosis, and apoptosis induced by thiamethoxam in the brains of male rats

Synthetic organic insecticides such as pyrethroids, organophosphates, neonicotinoids, and others have the potential to disrupt ecosystems and are often toxic to humans. Thiamethoxam (TMX), a neonicotinoid insecticide , is a widely used insecticide with neurotoxic potential. l-Carnitine (LC) is regarded as the “gatekeeper” in charge of allowing long-chain fatty acids into cell mitochondria. LC is an endogenous chemical that is renowned for its prospective biological activity in addition to its role in energy metabolism. This study investigated the protective effects of LC against TMX-induced neurotoxicity in male Wistar rats. For 28 days, animals were divided into four groups and treated daily with either LC (300 mg/kg), TMX (100 mg/kg), or both at the aforementioned doses. Our results revealed marked serum lipid profile and electrolyte changes, declines in brain antioxidants and neurotransmitters (acetylcholine, dopamine, and serotonin levels) with elevations in thiobarbituric acid reactive substances and proinflammatory cytokine levels, as well as acetylcholinesterase and monoamine oxidase brain activity in TMX-treated rats. TMX also increased the expression of caspase-3 and glial fibrillary acidic protein. In contrast, pretreatment with LC attenuated TMX-induced brain injury by suppressing oxidative stress and proinflammatory cytokines and modulating neurotransmitter levels. It also ameliorated the expression of apoptotic and astrogliosis markers. It could be concluded that LC has antioxidant, anti-inflammatory, anti-astrogliosis, and anti-apoptotic potential against TMX neurotoxicity.Graphical abstract

The Protective Role of L-carnitine on Psychosocial Stress-induced Changes in Gene Expression and Protein Levels of Matrix Metalloproteinases, Serum Corticosterone in a Rat Model.

Psychosocial stress (STS) is a common stress in modern societies. Chronic STS is associated with the impairment of a broad range of cognitive functions in humans and with prolonged abnormalities in memory. Matrix metalloproteinases (MMPs), a protein family of zinccontaining endopeptidases, are essential in neuro-inflammation and involved in neurodegenerative diseases. L-Car possessed neuroprotective, antioxidant, and anti-inflammatory properties and was shown to modulate MMPs. The current study aimed to examine the protective effect of L-Carnitine (L-CAR) on STSinduced changes in serum corticosterone levels, MMP-2, -9, and -12 protein and mRNA expression in the hippocampus as a possible mechanism for L-CAR protective effect on STS-induced memory impairment. The chronic STS and L-CAR (300 mg/kg/day, i.p) were simultaneously administered for 6 weeks to adult male Wistar rats. Serum corticosterone and protein levels of MMP-2, -9 and -12 were evaluated using ELISA. Real-Time PCR techniques were used to determine the mRNA levels of MMP-2, -9 and -12 in the hippocampus. The findings showed that serum corticosterone levels and MMP-2 and -9 protein levels were significantly increased (p<0.05) in the STS group compared to the control. Similarly, RT-PCR findings showed that the mRNA of those proteinases significantly increased (p<0.05) following the intruder method. On the other hand, the administration of L-CAR restored the alterations in corticosterone levels and MMPs gene and protein expression induced by chronic STS. STS induced elevations in corticosterone and MMP-2 and -9 levels in the hippocampus. L-CAR, on the other hand, exhibited protective effects against the STS-induced changes in MMP-2 and -9.

Histological study on the possible protective role of L-carnitine against testicular ischemia-reperfusion injury induced in rabbits

Histological study on the possible protective role of L-carnitine against testicular ischemia-reperfusion injury induced in rabbits

The protective role of l-carnitine against cisplatin induced testicular toxicity in the adult albino rat

The protective role of l-carnitine against cisplatin induced testicular toxicity in the adult albino rat

Possible Protective Role of L-carnitine against Cisplatin-induced Testicular Changes in Adult Male Albino Rats: A Histological and Morphometric Study

Possible Protective Role of L-carnitine against Cisplatin-induced Testicular Changes in Adult Male Albino Rats: A Histological and Morphometric Study

“Dose-Duration Dependent Changes Induced by Atrazine in the Ovary of Adult Albino Rat and the Possible Protective Role of L-Carnitine: Histological and Immunohistochemical Study”

Introduction: Atrazine (ATR) is the most common herbicide used in the world. Several studies show that ATR has many reproductive adverse effects. L-Carnitine (LC) is a flavonoid antioxidant.Aim of the Work: The goal of this research was to elucidate the structural and biochemical alterations induced by ATR in the ovary of the adult albino rats and to clarify the possible protective role of LC. Material and Methods: 70 adult female albino rats were separated into 6 groups; Control, LC (given 100 mg LC/kg/day for 30 days), ATR sub-chronic treated (given 6.5 mg ATR/kg/day for 30 days), ATR sub-acute treated (given 65 mg/kg/day for 14 days), Sub-chronic protected (given 6.5 mg ATR/kg/day +LC 100 mg/kg/day for 30 days), and Sub-acute protected (given 65 mg ATR/kg/day +LC 100 mg/kg/day for 14 days). All doses were administrated orally. Blood and tissue samples were obtained and processed for biochemical, histological, and immunohistochemical study. Statistical analysis was also done.Results: Serum luteinizing hormone (LH) and estradiol (E2), ovarian superoxide dismutase (SOD) and catalase (CAT) significantly decreased while the ovarian malondialdehyde MDA and nitric oxide (NO) significantly increased in ATR treated groups as compared to control group. Ovarian tissue of ATR treated groups showed significant increase in number of atretic follicles and loss zona pellucida continuity in PAS stain as compared to control group. Atresia was confirmed by significant increase in immuohistochemical study of P53 in ATR treated groups. Also, there was significant decrease in mitotic division in ATR treated groups confirmed by immuohistochemical study of Ki-67 as compared to control group. Moreover, there was significant difference between the two ATR treated groups in both biochemical and structural findings. While, these changes were less obvious in protected groups after administration of LC. Conclusion: supplementation of LC could have a beneficial effect against ATR-induced ovarian damage.

Possible protective role of l-carnitine against hyperthyroidism induced osteoporotic changes in femoral diaphysis of adult male albino rats

Possible protective role of l-carnitine against hyperthyroidism induced osteoporotic changes in femoral diaphysis of adult male albino rats

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).

The protective role of l-carnitine on spermatogenesis after cisplatin treatment during prepubertal period in rats: A pathophysiological study

AimsAs the spermatogenesis process is targeted by cisplatin (Cis) that changes testicular morphology, alters sperm quality, and hence causes male infertility. This study investigated the possible therapeutic effects of l-carnitine (LC) on Cis impaired spermatogenesis's establishment during the prepubertal phase. Materials and methodsNinety-six prepubertal Sprague Dawley male rats were divided into four groups. Control group: rats were injected with 0.9% saline solution intraperitoneally (i.p.). LC group: animals were injected for eight weeks, with 250 mg/kg/wk. LC (i.p.). Cis group: animals were injected with a single dose of 5 mg/kg Cis (i.p.). LC + Cis group: animals were pre-injected with LC 250 mg/kg 2 h before Cis injection. The rats were sacrificed at 37, 60, and 90 days old, and their testes were taken for biochemical, molecular, and histopathological studies. The motility, viability, morphology, and DNA fragmentation of sperm in adult rats were also measured. Key findingsGroup treated with LC and Cis showed an increase in antioxidant and hormonal activity compared to the Cis treated group in the pre and post-pubertal period. Moreover, there was an increase in sperm survival, motility, and DNA integrity. Furthermore, LC showed an increase in the anti-apoptotic and chromatin remodeling genes and a decrease in the pro-inflammatory genes. SignificanceLC could enhance the spermatogenesis process after exposure to Cis during the prepubertal phase by restoring the balance between reactive oxygen species and antioxidant activity, improving hormonal activity, sperm quality and DNA integrity, promoting protamination and blood-testis barrier integrity, and maintaining the testicular architecture.

Histological and immunohistochemical study on the effect of valporic acid on the bone of adult male guinea pigs and the possible protective role of L-carnitine

Background: Valporic acid (VPA) is a broad-spectrum antiepileptic drug and is effective in the treatment of different types of epileptic seizures. It usually affects bone and mineral metabolism and increase the risk of fractures due to decreased bone mineral density (BMD). Among dietary supplements, L-carnitine is an emergic candidate with potential bone protective effects. It promotes energy utilization and is important for tissues with high energy requirements.Objective: The target of this work is to estimate the effect of valproic acid on the femur and the possible protective effect of L-carnitine administration in adult male guinea pigs.Materials & Methods: Forty adult male guinea pigs were utilized in the current study. The guinea pigs were divided into four groups, Group I (control group), Group II(L-carnitine treated group), Group III (Valporic acid treated group) and Group IV (L-carnitine and valporic acid treated group). After 10 weeks, the upper parts of femur were processed for histological, morphological and immunohistochemical studies.Results: Valporic acid treated group was associated with enhanced bone turnover as evident by a significant change in serum levels of calcium, osteocalcin and TRAP. Moreover, there was a significant decrease in trabecular and cortical bone thickness and a significant change in the mean number of osteoclasts and osteoblasts. Histologically, evidence of bone resorption was manifested in the femoral bone with resorption cavities, irregular endosteal surface. Decrease of collagen in the cortical bone was evident in trichrome-stained sections. Immunohistochemically, this group showed positive immunoreactivity for caspase-3 in osteocytes and decrease in osteopontin expression in bone matrix. L-carnitine supplementation with valporic acid in group IV has ameliorating effect on the histological abnormalities of bone.Conclusion: L-carnitine improved the biochemical, histological and morphometric changes induced by VPA, and therefore, there is a potential benefit in using L-carnitine with long term administration of valporic acid.

Changes in Adult Rats’ Testis structure Induced by Hypothyroidism and Alleviating Role of L-Carnitine

Background Hypothyroidism is a metabolic disorder affecting the functions of many tissues in the body including the testis. Testis is rich in the polyunsaturated fatty acids content and lacks strong intrinsic antioxidant system making it prone to such oxidative stress. L-carnitine (LC) regulates long chain fatty acids metabolism; and is considered a valuable antioxidant factor. Aim It was to evaluate the effect of hypothyroidism induced by propylthiouracil (PTU) on rats’ testes and the possible protective role of LC. Methods Forty-eight adult male albino rats were used in this work. The animals were divided into three groups with sixteen animals in each. Group 1 (Control): Animals were kept without medications. Group 2 (PTU-treated): was subjected to administration of PTU; while group 3 (PTU and LC) received both PTU and LC. By the end of the experiment “30 days”, blood samples were taken for hormonal assay; then animals were anaesthetized and sacrificed. Specimens were homogenized for biochemical analysis; epididymal content of each rat was obtained immediately for semen analysis. Testes’ specimens were harvested, prepared and examined by light microscope examination. Results Induced hypothyroidism was noticed to cause histopathological, morphometric and biochemical changes in rat’s testes. LC protected the testicular specimens against such changes; it also improved the seminal quality and quantity as well as testicular structure and biochemistry. Conclusion Hypothyroidism could result in hazards to the structure of testis. Fortunately co-administration of LC might reduce such hazards.

The protective role of l-carnitine against 1st- and 2nd-generation antihistamine-induced liver injury in mice

H1 antihistamines are the most widely used drugs for relieving symptoms of histamine-mediated disease. Although chlorpheniramine maleate and cetirizine hydrochloride have tolerable side effects, they induce severe side effects on chronic use such as hepatitis and cholestatic jaundice. Oxidative stress has been implicated as a mechanism of drug-induced hepatotoxicity. l-Carnitine is an effective biological active compound that is involved in oxidation of fatty acids in the liver through transportation of fatty acids into the mitochondria for energy production from fat. l-Carnitine has well-known antioxidant properties, improves hepatic function, and improves mitochondrial function in hepatic cells. In the present study, we evaluated the possible role of oxidative stress and the therapeutic and hepatoprotective effect of l-carnitine on chlorpheniramine maleate– and cetirizine hydrochloride–induced liver damage during chronic use. Methods are measurement of ALT, AST, ALP and albumin serum levels and measurement of hepatic oxidative stress biomarkers MDA and GSH in groups with and without combination with l-carnitine. Histopathological examination of changes in hepatic tissue and scoring of the induced hepatic damage was conducted in all treatment groups. Co-treatment of l-carnitine with chlorpheniramine maleate and cetirizine hydrochloride significantly improved the deteriorated hepatic function as indicated by reduction in the serum levels of ALT, AST, ALP, and elevation in serum albumin levels compared with control and untreated groups. Moreover, co-administration of l-carnitine with chlorpheniramine maleate and cetirizine hydrochloride decreased hepatic MDA and elevated hepatic GSH levels compared with control and untreated groups. Ultrastructure examination of hepatic tissue found that co-treatment with l-carnitine decreased hepatic necrosis and damage. In conclusion, oxidative stress can be a possible explanation of hepatic damage induced by chronic therapy with chlorpheniramine maleate and cetirizine hydrochloride. l-Carnitine has prominent hepatoprotective effects on chlorpheniramine maleate– and cetirizine hydrochloride–induced hepatic damage possibly through improvement of hepatic function and decreasing oxidative stress.

Renal Cortical Structural Alterations in Atorvastatin-treated Rats and the Possible Protective Mechanisms of L-Carnitine

The present study investigated the structural changes in rat kidney following administration of atorvastatin and evaluated the possible protective role of L-carnitine. Rats were divided into four groups, group I- control group, group II received L-carnitine at 100 mg/kg/d, group III received atorvastatin at 80 mg/kg/d and group IV received atorvastatin plus L-carnitine. Hematoxylin and Eosin, periodic acid-Schiff, inducible nitric oxide synthase, proliferating cell nuclear antigen expression and electron microscopy investigation were performed. Light microscopy results of atorvastatin group showed severe atrophic glomeruli with widened glomerular spaces. Some renal tubules showed cytoplasmic vacuolations, loss of brush borders, hemorrhage and mild congested blood capillaries. Strong positive inducible nitric oxide synthase and proliferating cell nuclear antigen immunostaining in the tubules were observed. Ultrastructurally, the proximal convoluted tubules had small electron dense nuclei, numerous lysosomes, partial loss of microvilli and vacuolations. The podocytes revealed united foot processes and increase in the thickness of the glomerular basement membrane. L-carnitine preserved the structure of renal cortex, decreased inducible nitric oxide synthase and increased proliferating cell nuclear antigen reaction. In conclusion, atorvastatin exerted a deleterious effect and L-carnitine improved most of the histological changes produced by atorvastatin.

Effect of exposure to cadmium on the hippocampus in adult albino rat and the possible role of L-carnitine

Background The hippocampus is an important structure for formation of new memories. Cadmium is one of the most toxic agents that can affect hippocampal neurons. L-carnitine is an antioxidant. Aim of work To demonstrate the effects of cadmium on principal cells of hippocampus of adult rats and possible protective role of L-carnitine. Materials and methods A total of 42 adult rats aged 1 month were subdivided into four subgroups: group I was the control group, which received no treatment. Group II was administered cadmium given at a dose of 4 mg/kg/day for 1 month. Group III (sham control) was administered L-carnitine given at a dose of 200 mg/kg/day for 1 month. Group IV was administered cadmium and L-carnitine given to the rats at the same previous doses and duration. For each group, six rats were used for light microscopic study (gallocyanin chrom alum stain), and six rats were used for electron microscopy (group III studied only by light microscopy). Principal cell count and thickness were measured and statistically analyzed. Results Principal cells in group II showed degenerative changes. Morphometric data showed a significant decrease in measured parameters. In group III, the results were similar to those of the control group. In group IV, semithin sections and the ultrastructure of the principal cells showed obvious improvement of cells. Morphometric data also increased compared with those treated with cadmium. Conclusion Cadmium induces changes in the structure of the principal cells of the hippocampus in adult rats. L-carnitine plays an important in protection of the hippocampus.

Effect of Experimentally Induced Hypothyroidism on Structure of Adult Albino Rats’ Testes and Possible Protective Role of L-carnitine

Effect of Experimentally Induced Hypothyroidism on Structure of Adult Albino Rats’ Testes and Possible Protective Role of L-carnitine

Monosodium Glutamate Toxicity and the Possible Protective Role of L–Carnitine

Monosodium glutamate is naturally available non-essential amino acids, which found in naturally occurring foods and used as flavour enhancer worldwide. Monosodium glutamate is believed to be linked with diverse health problems. The aim of the study was toxic effects of monosodium glutamate (MSG) and the protective role of L-carnitine, light on the available literature from last 25 years about diverse toxicity studies which had been carried out on animal and human models. Google scholar, NCBI, PUBMED, EMBASE, Wangfang databases, and Web of Science databases were used to retrieve the available studies. MSG was linked with deleterious effects particularly in animals including induction of obesity, diabetes, hepatotoxic, neurotoxic and genotoxic effects showed in Literature. Few reports revealed increased hunger, food intake, and obesity in human subjects due to MSG consumption. Hepatotoxic, neurotoxic, and genotoxic effects of monosodium glutamate on humans carried out very limitedly. High consumption of monosodium glutamate may be linked with harmful health effects showed in available literatures. So, it is recommended to use common salt instead of MSG. Furthermore, intensive research is required to explore monosodium glutamate–related molecular and metabolic mechanisms. L-carnitine can protect from Hepatotoxic, neurotoxic, renal impairment and genotoxic effects functionally, biochemically and histopathologically with a corresponding reduction of oxidative stress.

Cancer Induced Infertility and the Role of L-Carnitine: A Review for Possible Future Clinical Applications

Context: Epididymis is highly rich by L-carnitine (LC), which serves as a protectant agent for the oxidation process and also has key roles in energy production and motility enhancement. Progress in cancer survivor beside dramatic increase in cancer prevalence has led to universal interest for fertility preservation in survival of patients with cancer. Recently, a trend is established for evaluating the effects of LC and its ester supplementation on radio and chemotherapy induced gonadal injury. This article focused on chemotherapy induced infertility, mechanisms involved, and the possible protective role of LC. Evidence Acquisition: All papers including clinical trials, case reports, case series, and reviews on the role of LC in the cancer induced infertility were obtained by searching in medical publications such as Elsevier, PubMed, Google Scholar, and clinical trials. Results: L-carnitine pre-treatment was effective in improving sperm parameters, especially total motility, viability, reducing cell apoptosis; it was also able to promote the quality of the semen exacerbated by chemotherapy agents such as etoposide, doxorubicin, and cyclophosphamide in animal model. Conclusions: According to animal studies, the administration of LC could show a promising protective data, but before any judgment, further large controlled studies are required and issue is matter of concern in future studies.

Effect of ischemia–reperfusion on the renal cortex of adult male albino rat and the possible protective role of l-carnitine

Effect of ischemia–reperfusion on the renal cortex of adult male albino rat and the possible protective role of l-carnitine

Inflammatory and fibrotic processes are involved in the cardiotoxic effect of sunitinib: Protective role of L-carnitine.

Sunitinib (Su) is currently approved for treatment of several malignances. However, along with the benefits of disease stabilization, cardiovascular toxicities have also been increasingly recognized. The aim of this study was to analyze which mechanisms are involved in the cardiotoxicity caused by Su, as well as to explore the potential cardioprotective effects of l-carnitine (LC). To this end, four groups of Wistar rats were used: (1) control; (2) rats treated with 400mg LC/kg/day; (3) rats treated with 25mg Su/kg/day; and (4) rats treated with LC+Su simultaneously. In addition, cultured rat cardiomyocytes were treated with an inhibitor of nuclear factor kappa B (NF-κB), in order to examine the role of this transcription factor in this process. An elevation in the myocardial expression of pro-inflammatory cytokines, together with an increase in the mRNA expression of NF-κB, was observed in Su-treated rats. These results were accompanied by an increase in the expression of pro-fibrotic factors, nitrotyrosine and NOX 2 subunit of NADPH oxidase; and by a decrease in that of collagen degradation factor. Higher blood pressure and heart rate levels were also found in Su-treated rats. All these alterations were inhibited by co-administration of LC. Furthermore, cardiotoxic effects of Su were blocked by NF-κB inhibition. Our results suggest that: (i) inflammatory and fibrotic processes are involved in the cardiac toxicity observed following treatment with Su; (ii) these processes might be mediated by the transcription factor NF-κB; (iii) LC exerts a protective effect against arterial hypertension, cardiac inflammation and fibrosis, which are all observed after Su treatment.