Micronutrient antioxidant status in black South Africans with chronic pancreatitis: opportunity for prophylaxis.

Biochemical assessments of micronutrient antioxidant status were done in 14 consecutive black patients with calcific chronic pancreatitis and 15 controls at Soweto, near Johannesburg in southern Africa. The patients showed subnormal levels of vitamin C in plasma; selenium, beta-carotene and alpha-tocopherol in serum; and inorganic sulphate (as an index of long-term sulphur amino acid intake) in urine (P < 0.001 for each): furthermore, among the patients ascorbate constituted a lower fraction of vitamin C (P < 0.002), indicating heightened oxidation of the bioactive form. By comparing the results in Sowetan controls with reference ranges from Manchester, UK, the markedly lower vitamin C and, hence, ascorbate levels in the Sowetans was underlined (P < 0.001) and their selenium levels were also lower (P < 0.001), but beta-carotene, alpha-tocopherol and inorganic sulphate levels were comparable. The very low bioavailability of ascorbate among Sowetan controls is reminiscent of our previous finding in outwardly healthy people at Madras in southern India: in both these areas chronic pancreatitis is currently endemic, has a propensity to pancreatic calculi and runs a virulent course towards premature death from diabetes, malnutrition or pancreatic cancer. Considering that low ascorbate levels are a feature in patients with chronic pancreatitis who develop pancreatic calculi at Manchester and that antioxidant supplements ameliorate painful symptoms, we suggest that poor antioxidant intake may predispose underprivileged tropical communities to the disease. If so, there could be an opportunity for prophylaxis through a daily tablet containing vitamin C, perhaps along with selenium at Soweto and beta-carotene at Madras.

Evidence for early oxidative stress in acute pancreatitis. Clues for correction.

Pancreatic oxidative stress with depletion of pancreatic glutathione is an early feature in all tested models of acute pancreatitis, and sooner or later the problem extends to the lung, irrespective of disease severity, whether toward spontaneous recovery or death from multisystem organ failure. We, therefore, sought evidence of oxidative stress in the human disease by analyzing admission blood samples. We found it from high concentrations of oxidatively altered linoleic acid in serum and vitamin C in plasma (p < 0.001 vs controls or a group of other acute abdominal crises where the proportion of patients with admission Apache II scores < or > 8 was similar). These changes were accompanied by subnormal levels of ascorbic acid in plasma (p < 0.001); selenium (p < 0.001), beta-carotene (p < 0.001), and alpha-tocopherol in serum (p = 0.005 for its molar ratio to cholesterol). Paradoxically, the plasma concentration of S-adenosylmethionine was elevated (p = 0.02), suggesting that this proximate bioactive metabolite of the essential amino acid had backtracked because its intracellular metabolism down the methionine trans-sulfuration pathway toward glutathione synthesis was disrupted. The aberrations transcended putative etiological factor, duration of symptoms, or disease severity. We conclude: (1) that oxidative stress has pervaded the vascular compartment by the time of admission in patients with acute pancreatitis, and, (2) that blood micronutrient antioxidant profiles at this stage are consistent not only with compromised intracellular capacity to synthesize/refurbish glutathione, but also vulnerability of intra- and extracellular lipid targets.

Heightened free radical activity in blacks with chronic pancreatitis at Johannesburg, South Africa.

Four indices of free radical activity were measured in fasting serum/plasma samples from 14 consecutive blacks with clinically quiescent chronic pancreatitis and 15 outwardly healthy hospital personnel at Soweto, the township near Johannesburg in South Africa. The patients had higher serum levels than did controls of lipid isomerisation (P < 0.002) and peroxidation (P < 0.05) markers, with lower plasma levels of glutathione (P < 0.0001) and bioactive fraction of vitamin C (P < 0.002). Lipid peroxide and non-bioavailable vitamin C concentrations in Sowetan patients were significantly higher than in their counterparts from Manchester, UK (P < 0.0001, P < 0.0005, respectively). These differences mirrored those in controls in that outwardly healthy Sowetans had much higher serum lipid peroxide levels than Manchester controls (P < 0.001) and much lower plasma concentration of vitamin C (P < 0.001) and hence of the bioavailable fraction ascorbate (P < 0.0002). Heightened free radical activity is thus a common denominator in chronic pancreatitis irrespective of geography, or putative aetiological factors whether alcoholism or idiopathic, since that ratio was approximately 95:5 at Johannesburg and 50:50 at Manchester. The further finding of subclinical oxidative stress in Sowetan controls and the endemic nature of chronic pancreatitis in that area supports the hypothesis that oxidative stress may be involved in its pathogenesis.

Vitamin C status in patients with acute pancreatitis.

Vitamin C is a key antioxidant in human blood plasma and hence could influence the outcome of conditions such as acute pancreatitis in which oxidative stress apparently plays a pivotal role. The concentrations of vitamin C and its immediately bioavailable form, ascorbic acid, in fasting plasma samples from 30 healthy volunteers were compared with those in admission samples from 29 consecutive patients with acute pancreatitis and 27 patients with other acute abdominal crises. Median (range) levels of vitamin C and ascorbic acid, respectively, were 15 (6.3-19) and 12 (4.5-18) micrograms/ml in the control group, 2.8 (0.3-10) and < 0.5 (< 0.5-6.0) micrograms/ml in patients with acute pancreatitis, and 3.7 (0.6-15) and 2.3 (< 0.5-15) micrograms/ml in those with other acute abdominal problems. Admission plasma samples showed equally low vitamin C levels in both groups of patients (P < 0.001 versus controls), but those from patients with acute pancreatitis were further characterized by a disproportionate reduction in ascorbic acid, such that the concentration of ascorbic acid and its ratio to vitamin C were both significantly lower than in samples from patients with an acute abdomen (P < 0.005 and P < 0.001 respectively). It is concluded that the stress of an acute intra-abdominal crisis is accompanied by a non-specific decrease in the plasma level of vitamin C. In acute pancreatitis early and profound oxidative stress compounds this problem by denaturing the available vitamin. There may be a case for the judicious parenteral administration of ascorbic acid to patients with acute pancreatitis to boost plasma antioxidant defence.