الفهرس 
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Abstract
Worldwide, cancer has been found to be a major cause of illness and death. Chemotherapy is vital for cancer prevention and treatment. 5-Fluorouracil is one of the most effective chemotherapy drugs for treating a variety of tumor types. Despite 5-FU’s ability to treat cancer, it has significant adverse effects that include hepatotoxicity and nephrotoxicity. In cancer therapy, drug delivery systems are currently attracting a lot of interest for controlling the cytotoxic effect of chemotherapy on healthy cells. Because they may deliver anticancer medicines to specific sites and release the drug continuously and under control, nanoparticles serve as drug carriers and interact with certain ligands. Certain biological components, including l-carnitine, have significant anti-inflammatory and anti-cancer properties due to their many beneficial actions on different biological molecular targets. L-carnitine is a physiologically active stereoisomer with a diversity of characteristics, including hydrophobicity, biodegradability, and high biocompatibility. The potential effects of Nano l-carnitine on hepatotoxicity, renal damage, and the enhancement of liver and kidney functions have sparked a great deal of interest recently. It removes free radicals and ROS from the body and has anticancer properties.
The aim of the recent investigation was to evaluate Nano l-carnitine’ anticancer effectiveness and safety in mice with Ehrlich solid carcinoma as compared to the commercial medication 5-FU.
The current study employed 247 female Swiss albino mice weighing 25-30 grams each. The animals were separated into two major categories:
1. Anti-tumor Studies
172 mice with solid Ehrlich carcinoma were tested to determine the anti-tumor activities of 5-FU and/or 5-FU+NLC. The mice were divided into two groups: group A (32 mice) for calculating the mortality rate and group B (140 mice) to determine the mean tumor weight.
A. Mortality rate
32 mice were divided into four groups (n=8) and used for estimating the mortality rate as flow:
group 1EAC Female mice were inoculated with (2.5 × 106 )
Viable EAC cells intramuscularly in their left thighs.
group 2 EAC+5-FU Female mice with EAC were treated with 5-FU (20mg/kg), i.p. three times each week for three weeks.
group 3 EAC+NLC Female mice bearing EAC, treated with orally with NLC (50mg/kg) three times every week for three weeks
group 4 EAC+ 5-FU+NLC Female mice with EAC cells cured with 5-FU and NLC as the same prior dose, duration, and mode of administration.
B. The mean tumor weight
The second group of 140 mice has been employed to determine the mean tumor weight (MTW) until the last day of the study, and they were separated into four groups (n = 35) as follows: Gr1: EAC, Gr2: EAC+5-FU, Gr3: EAC+NLC, and Gr4: EAC+5-FU+NLC (the animals in these groups were given injections as previously stated).
Biochemical and histological investigations.
The 75 mice were divided into 5 groups of 15 mice.
group 1
CON Normal control group (CON) injected with physiological saline.
group 2 EAC Female mice were administered with (2.5 × 106)
Viable EAC cells intramuscularly in their left thighs.
group 3 EAC+5-FU Female mice bearing EAC, treated with 5-FU (20mg/kg), i.p. three days per week for three weeks.
group 4 EAC+NLC Female mice bearing EAC, treated with orally with NLC (50mg/kg) three days a week for three weeks
group 5 EAC+ 5-FU+NLC Female mice having EAC cells cured with 5-FU and NLC as the same prior dose, duration, and mode of administration.
The study’s mice were all dissected at the conclusion of the investigation. Serum was extracted from blood samples that were taken. The liver and kidney organs were removed for histological analysis. Samples were obtained from the kidney and liver for biochemical analyses. These analyses measured oxidative stress, such as the rate of MDA lipid peroxidation, and included some antioxidants, such as SOD, glutathione GSH, and glutathione peroxidase GPX. Tumor necrosis factor alpha (TNF-α) and (MCP-1) were two other inflammation indices that were assessed. Samples of the liver and kidney were obtained in order to quantify CRP and liver alpha gene protein (AFP), as well as the apoptosis indices caspase-3 and p53 and the anti-apoptotic protein Bcl2.
Additionally, AST and ALT aminotransferase liver enzymes were measured in the blood. Measurements were also made of renal albumin, urea, and creatinine.
The end results of the current investigation were as follows:
The results revealed that there were no changes between the group of Nano l-Carnitine and the normal control group.
The administration of 5-FU+NLC led to a decrease in mean tumor weight (MTW) in EAC mice, an enhancement in MST, and an extension in increased life span (ILS) in contrast to the administration of 5-FU alone.
When 5-FU was given to EAC mice, the antioxidant components SOD, GSH, and GPX were reduced and significantly increased MDA levels in the liver and kidney tissues. On the other hand, oxidative and anti-oxidant variables clearly improved after the 5-FU+NLC treatment.
Frequent 5-FU treatment raised the inflammatory markers TNF-α and MCP-1 in liver and kidney tissues. However, 5-FU+NLC therapy reduced these markers.
When 5-FU+NLC was administered, caspase-3 and p53 were reduced, which define the apoptotic markers, and Bcl2 was also elevated, which defines the anti-apoptotic protein.
The use of 5-FU elevates the levels of CRP and AFP in the liver tissues. Along with an increase in creatinine, urea, and albumin levels in the kidney, there was also an increase in ALT and AST in the liver tissues. However, these levels improved following the 5-FU+NLC treatment.
Comparatively speaking, the 5-FU+NLC treated mice’s liver and kidney tissue sections showed fewer histological lesions than the EAC and 5-FU treated groups’ liver and kidney tissue sections, which featured more lesions overall.
Due to the active role of 5-FU+NLC as an antioxidant, anti-inflammatory, and anti-apoptotic, this study’s conclusion is that using Nano l-carnitine increases the efficiency of 5-fluorouracil in fighting tumors by decreasing tumor weight and lengthening life span, in addition to reducing toxicity to vital organs.
Given the above, it is preferable to adopt contemporary nanometric techniques to guard against the toxicity that 5-fluorouracil cause in mice.