Plasma concentrations of alpha-tocopherol and urate in patients with different types of cancer.

OBJECTIVE: To measure plasma concentrations of alpha-tocopherol and urate to determine whether there is any relationship with different types of cancer before treatment. METHOD: Plasma concentrations of those two antioxidants were measured in cancer patients and sex- and age-matched controls. Plasma total cholesterol concentration was measured to derive an alpha-tocopherol/cholesterol ratio. RESULTS: Alpha-tocopherol and urate concentrations as well as alpha-tocopherol/cholesterol ratios were significantly lower in the cancer patients as whole, in gastrointestinal cancer and in breast cancer compared to the controls. There was no significant relationship between alpha-tocopherol and urate levels in either the plasma of patients (r=0.048; P=0.653) or controls (r=0.073; P=0.406). Alpha-tocopherol was more positively correlated with cholesterol in the plasma of controls (r=0.539; P < 0.0001) in comparison with the patients (r=0.456; P < 0.0001). There was no significant correlation between urate and cholesterol levels in both patient and control plasma samples. CONCLUSION: The data suggest that although alpha-tocopherol and urate provide important antioxidant defence in cancer, the association between their levels is weak.

Plasma micronutrient antioxidant in cancer patients.

The distribution of breast, colon, gastric, thyroid, oral, rectal, pancreatic and renal cancers were determined in 71 Kuwaitis, 45 other Arabs, and 26 Indians. Plasma levels of micronutrient antioxidants, retinol, alpha-tocopherol, lycopene, and beta-carotene were measured in the groups and in 90 matched controls for comparison. Cholesterol was measured to determine its association with the micronutrient antioxidants. Pancreatic cancer occurred exclusively in Kuwaitis, while breast and colon cancers were disproportionately higher in Kuwaitis than in the other groups. Micronutrient antioxidant levels were similar in the groups, except for higher lycopene levels in Kuwaitis. In most instances, the micronutrient antioxidants, except beta-carotene, decreased significantly in levels in patients than in controls. Low levels of retinol, lycopene, and beta-carotene were strongly associated with pancreatic cancer. Compared to controls, significantly increased levels of beta-carotene occurred in breast, colon, thyroid, and renal cancers; increased lycopene occurred in oral cancer, and increased alpha-tocopherol occurred in pancreatic cancer. Alpha-tocopherol strongly correlated with cholesterol. Generally, changes in alpha-tocopherol/ cholesterol ratios mimicked those of alpha-tocopherol levels. Micronutrient antioxidant levels were significantly lower in male patients than female patients. Age showed a negative but statistically insignificant relationship with micronutrient antioxidants. Lycopene strongly correlated with alpha-carotene and alpha-tocopherol with retinol. Among the patients, all micronutrient antioxidants except retinol decreased significantly in levels in smokers than nonsmokers, suggesting susceptibility to cigarette smoke oxidative stress. We conclude that micronutrient antioxidant depletions and altered associations may imply tumor utilization or antioxidant burden in oxidative stress or both. Furthermore, the incidence of pancreatic, colon and breast cancers among Kuwaitis warrants further study.

Serum antioxidant and cholesterol levels in patients with different types of cancer.

Serum antioxidant (urate, alpha-tocopherol) activity and cholesterol concentration in 142 patients of Indian and Arab (Kuwaitis and other Arabs) origin with different types of cancer (breast, colon, stomach, thyroid, oral, rectal, pancreatic, and renal) were compared to 100 age- and sex-matched control subjects. Values were expressed as medians (interquartile range). Urate concentration was significantly decreased in male patients compared to male controls (P < 0.0001) and in female patients and female breast cancer cases compared to female controls; P < 0.0001 and P = 0.001, respectively. Alpha-tocopherol concentration decreased significantly in total cancer, stomach, colon, rectal, and breast cancer cases than the controls; P < 0.0001, P < 0.0001, P < 0.0001, P = 0.012, and P = 0.022, respectively. Cholesterol concentration decreased significantly in stomach, oral, colon, and total cancer cases compared to the controls; P < 0.0001, P < 0.0001, P = 0.002, and P = 0.012, respectively. Among controls, females had significantly (P < 0.0001) lower concentrations of alpha-tocopherol than males. Among patients, cholesterol, urate, and alpha-tocopherol concentrations decreased significantly in smokers than in nonsmokers; P < 0.0001, P = 0.004, and P = 0.047, respectively. Generally, changes in alpha-tocopherol/cholesterol ratios mimicked changes in alpha-tocopherol concentration. Concentrations of all parameters decreased significantly in male patients compared to male controls. Age was positively associated with all three analytes with respect to the controls. Alpha-tocopherol correlated with cholesterol in cancer patients (r = 0.367; P < 0.0001) and with urate in the controls (r = 0.342; P < 0.0001). The data suggest cancer-related diminished synthesis of cholesterol and, generally, a greater antioxidant burden for alpha-tocopherol than urate in cancer-generated oxidative stress. The increased incidence of pancreatic cancer in Kuwaitis warrants further study.

The influence of brain acetaldehyde on oxidative status, dopamine metabolism and visual discrimination task.

The toxic effect of acetaldehyde on brain oxidative capacity and dopamine metabolism has been investigated in rat brains after a single intraperitoneal injection of acetaldehyde (5 mmol/kg) and the results compared with those from chronically ethanol fed rats. Acetaldehyde was present in rat brain 120 hr after a single dose of acetaldehyde, confirming that it is able to cross the blood-brain barrier. Brain catalase increased significantly after acetaldehyde or chronic ethanol administration although there were no other significant changes in the total brain activity of superoxide dismutase, glutathione peroxidase or glutathione reductase. Dopamine turnover was increased in both experimental groups. The acute dose of acetaldehyde reduced the ability of the rats to relearn a computer visual discrimination task.

Biochemical and biophysical investigations of the ferrocene-iron-loaded rat. An animal model of primary haemochromatosis.

Male Wistar rats fed with ferrocene had high hepatic iron loading (7.24 +/- 1.97 mg Fe/g tissue) after 6 weeks, principally located in lysosomes, which was comparable to the levels and distribution determined in human haemochromatosis. The two iron-storage proteins, ferritin and haemosiderin were isolated from the livers of the ferrocene-loaded rats and their iron cores were investigated by Mössbauer spectroscopy and inductively coupled plasma-emission spectrometry. Ferrihydrite was the predominant form of iron present in both ferritin and haemosiderin, while haemosiderin contained higher amounts of phosphorus, magnesium, calcium and barium, then either normal or ferrocene-loaded ferritin. Free-radical-mediated damage in the iron-loaded livers was inferred by the significant depletion of alpha-tocopherol in both the livers and subcellular hepatic lysosomal fraction, which inversely correlated with the increasing iron content (r = -0.61; P less than 0.05) and was associated with increased fragility of the lysosomal membranes.

Biochemical studies in paraplegic renal stone patients. 2. Urinary excretion of citrate, inorganic pyrophosphate, silicate and urate.

The urinary excretions of citrate, inorganic orthophosphate and pyrophosphate, silicate and urate were measured in 17 paraplegic patients with renal calculous disease associated with urinary infection, in 16 paraplegics with no history of urinary calculus and in 14 healthy control subjects. The paraplegics excreted less citrate, orthophosphate and pyrophosphate than the control subjects. The stone-formers excreted more urate than the paraplegics without stone disease, but less than the control subjects. There were significant positive correlations between urinary orthophosphate and pyrophosphate and between urinary silicate and 24-h urine volume. The possible roles of increased urate and diminished excretion of citrate and inorganic pyrophosphate in the aetiology of renal calculosis in paraplegic patients deserve further investigation.