P53 Sensitizes human colon cancer cells to hesperidin through upregulation ofbaxand p21

Hesperidin, a flavonoid found mainly in citrus, was reported to inhibit growth and proliferation of several cancers, including colon cancer cells. However, the question does p53 tumor suppressor protein is required for the effect of hesperidin is not yet clarified. In the present study, the effect of hesperidin on p53-expressing [HCT116 p53[+/+]] and p53-knockout [HCT116 p53[+/+] human colon cancer cells was investigated. Hesperidin inhibits cell growth of both HCT116 p53[+/+] and HCT116 p53 [A]cells, however, it was more effective in p53-expressing cells. Hesperidin induced Gl cell cycle arrest in only HCT116 p53[++] cells however induction of reactive oxygen species [ROS] and apoptosis was induced in both cells. Furthermore, hesperidin activates the proapoptotic [Bax] and cyclin dependent kinase inhibitor [p21] in only HCT116 p53[+/+] cells. Interestingly, using p53 transcriptional inhibitor [pifithrin-alpha] hesperidin-inducing Bax and p21 upregulation in only HCT116 p53[+/+] cells was reduced by cotreatment with pifithrin-alpha without inducing any changes in HCT116 p53-/- cells. Altogether; these results showed that hesperidin induced apoptosis and Gl cell cycle arrest in colon cancer cells in a p53/Bax - dependent and- independent, and p53/p21 - dependentmanners; respectively

Ultrastructural and histological studies on the ameliorative effects of some antioxidants on liver tissue of aged mice

One of the biological changes associated with aging is increased free radical formation, with subsequent damage to cellular processes. Aging increased oxidative injury and apoptosis in the liver of aging animals. Antioxidants play an important role in preventing free radical damage associated with age by interfering with the generation of these radicals or by scavenging them. This study were done to know the capability of damage and dysfunction of liver and the ameliorative effects of some antioxidants. Vitamin E [1.56 mg/kg] as lipid soluble antioxidant, vitamin C [1.9 mg/kg] as water soluble antioxidant and zinc sulfate [0.12 mg/kg] as metalloenzyme antioxidant were orally administrated to different groups of 15 months [aged] mice each for 30 consecutive days to improve age-associated liver dysfunction. The present study showed that zinc treatment of aged mice was associated with a significant increase in glycogen granules storage and protein deposition in the hepatocyte, also histological improvement in the liver architecture was noticed as an organized cords, intact hepatocytes cytoplasm without vacuolation and the nucleus were of normal size and blood sinusoids were more or less similar to those of the liver of adult animals, while treated with vitamin E appeared nearly normal with some little vacuoles in the cytoplasm of its cells, and high increase of glycogen and protein contents was observed in the hepatocytes. Vitamin C treatment showed fairly improvement to the general architecture of the liver tissue while the hepatocytes still showed vacuolated cytoplasm, and moderate increase in glycogen and protein content were observed in the hepatic cells. The present study suggested that zinc sulfate is the best antioxidant improve aging liver histology, then, vitamin E and vitamin C. Administration of these drugs where there is no need have bad and dangerous effects

Effect of increase in antioxidants supplementation on kidney tissue of mice subjected to fractionated dose of gamma-irradiation

Although there is little doubt that antioxidants are a necessary component for good health, no one knows if supplements should be taken and, if so, how much. To investigate the increase in antioxidants supplementation, a group of mice feeding on a diet containing 20% soybean was used as control group. The control group treated with 5% Nigella sativa and Antox drug [3 mg/mouse/day] either alone or in combination for 15 days. Another control group was treated with the same antioxidants and subjected to 1 Gy of gamma- irradiation x 5 times day after day. In kidney tissue the levels of malonaldehyde [MDA] and reduced glutathione [GSH] were estimated. Also, the histopathological changes were recorded. 5% Nigella sativa revealed a little decrease in MDA level and a highly significant decrease in GSH in kidney tissue while the exposure to fractionated dose of gamma-irradiation predicted a highly significant decrease in MDA and a highly significant increase in GSH level. Gastric intubations of Antox drug showed a highly significant increase in MDA and GSH levels in kidney tissue either alone or in addition to fractionated radiation exposure. Combined treatments of Nigella sativa and Antox drug showed a highly significant decrease in MDA level and a highly significant increase in GSH level in kidney tissue in comparison to the control group. Histopathological changes showed that treatment with 5% Nigella sativa and Antox drug either alone or in combination revealed toxic effect on kidney tissue. However, their treatments prior to radiation exposure showed ameliorating effect. Our findings indicated that we must use the antioxidants under control or under oxidative stress

Reversibility of age-related immune dysfunction in mammals by a combined treatment of some trace elements and vitamins

Immune responses normally reduced during aging may be resulted to different extends by the intake of several essential micro- and macronutrients. The aim of the present study was to investigate the in vivo effect of different doses of hepanox on humoral and cell-mediated immune responses of aged-mice in a trial to improve age-associated immune dysfunction. Different doses of hepanox [0.4, 2 or 10 micro g/mouse] were orally administrated to aged mice daily for one month. Control mice were treated with 0.2 ml of the sesame oil only. Our study shows that total leukocyte counts from PBL, Thy, PLN, MLN and BM as well as total and differential counts of PEC were significantly decreased in aged mice. Treatment of aged mice with hepanox preparations [0.4, 2 or 10 micro g/mouse] caused a progressive increase in the total numbers of leukocytes from all lymphoid organs studied. The present study shows also that the phagocytic function of PEC decreased with age of mice, while treat-ment of aged mice with hepanox preparation elicited a progressive increase in the scavenger activity of PEC. In old mice, there is a significant decline in PFC response to in vivo immunization with SRBC while the treatment of aged mice with hepanox preparation elicited a gradual increase in PFC response. Also, the number of T-lym-phocytes decreased significantly with advancing age of mice. Treatment of aged mice with hepanox preparations [2 and 10 micro g/mouse] elicited a progressive increase in the number of T-lymphocytes. While in vitro addition of hepanox preparations [0.002, 0.01 or 0.05 micro g/well] to old mice splenocytes, stimulated with Con A mitogen, sig-nificantly increased T-cells proliferation. The treatment of aged-mice with hepanox might be capable of main-taining and restoring the aged-related reduction in the immune efficiency

Piroxicam-induced hepatic and renal histopathological changes in mice

Piroxicam is a non-steroidal anti-inflammatory drug widely used in rheumatic diseases. The aim of this study was to investigate Piroxicam-induced histopathological changes in livers and kidneys of male albino mice. Animals were classified into a control group and 4 treated groups. Piroxicam was injected intraperitoneally using 0.3 mg/kg every day for four weeks. Each week a group of mice was sacrificed. Liver and kidneys were obtained for histological and histochemical examination. Animals were classified into a control group and 4 treated groups. Piroxicam was injected intraperitoneally using 0.3 mg/kg every day for four weeks. Each week a group of mice was sacrificed. Liver and kidneys were obtained for histological and histochemical examination. Liver sections appeared with inflammatory cellular infiltration, vacuolated hepatocytes, dilated sinusoids, and increased number of Kupffer cells. Kidney sections appeared with some cellular inflammations. The glomeruli were shrunk resulting in widening of the urinary space. Oedema and vacuolations were noticed in the tubular cells. There was a positive correlation between these pathological changes and the increased treatment periods. Histochemical staining revealed that glycogen and protein contents had decreased in the hepatocytes. This depletion worsened gradually in liver cells after two, three, and four weeks. Similar depletion of the glycogen content was observed in kidney tissue. However, protein content appeared to be slightly decreased in the kidney tubules and glomeruli. Incensement of coarse chromatin in the nuclei of hepatocytes, Kupffer cells and most inflammatory cells were detected by Fuelgen method. Kidney tissues appeared with a severe decrease in coarse chromatin in the nuclei. Liver sections appeared with inflammatory cellular infiltration, vacuolated hepatocytes, dilated sinusoids, and increased number of Kupffer cells. Kidney sections appeared with some cellular inflammations. The glomeruli were shrunk resulting in widening of the urinary space. Oedema and vacuolations were noticed in the tubular cells. There was a positive correlation between these pathological changes and the increased treatment periods. Histochemical staining revealed that glycogen and protein contents had decreased in the hepatocytes. This depletion worsened gradually in liver cells after two, three, and four weeks. Similar depletion of the glycogen content was observed in kidney tissue. However, protein content appeared to be slightly decreased in the kidney tubules and glomeruli. Incensement of coarse chromatin in the nuclei of hepatocytes, Kupffer cells and most inflammatory cells were detected by Fuelgen method. Kidney tissues appeared with a severe decrease in coarse chromatin in the nuclei. Piroxicam has a time-dependent toxic effect on both liver and kidney tissues

Modulation of induced cardiocytotoxicity and genotoxicity of doxorubicin in rat by L-carnitine

Doxorubicin [DOX] is an anthracycline antibiotic with broad-spectrum antitumor activity. Its effectiveness has been limited by the occurrence of dose related myocardial and bone marrow toxicity. L-carnitine is tested in this study to evaluate its protective effect against DOX induced cytotoxicity and genotoxicity. Four groups of adult female rats, each of 15 animals were used; one is used as control receiving 0.5 ml of saline, the other groups received either DOX [3mg/kg], L-carnitine [100mg/kg] or a combination of the two drugs. The treatment was continued i.p. every other day for two weeks. Five animals of each group were injected with 0.2ml of colchicine 2 h before sacrifice, which took place 24 h after the last treatment. Cardiotoxicity was assessed by measuring the serum levels of lactic acid dehydrogenase [LDH], creatine phosphokinase [CPK], glutamic oxaloacetic transaminase [GOT]. Reduced glutathione [GSH], malonaldehyde [MDA] and mitochondrial palmitoyl Co-A and octanoate oxidation were also, determined in cardiac tissue homogenate. The femurs were removed and bone marrow was processed for the preparation of metaphase chromosomes and determination of mitotic activity. DOX significantly increased LDH, CPK, GOT and MDA and significantly decreased GSH and palmitoyl Co-A. Administration of L-carnitine one hour before DOX treatment caused significant recovery for the serum enzymes LDH, CPK, GOT, and MDA, GSH and palmitoyl Co-A. Cytogenetic analysis showed that DOX increased the incidence of chromosomal aberration 18.4% in bone marrow cells and inhibited mitosis to about 50% of its normal rate. Administration of L-carnitine one hour before treatment with DOX significantly decreased the incidence of chromosomal aberrations [14.8%] and increased mitotic activity [10.4]. The results suggest that the cardiotoxicity and genotoxicity induced by DOX took place via a number of possible mechanisms. The results obtained suggest that L-carnitine could be used together with DOX as an adjuvant therapy