The observation that ascorbate known to retain pro-oxidant properties induces cell death in a number of immortal cell lines, led us to examine its mechanism and whether it is involved in oxidative stress injury in such asocorbate-enriched tissue cells as hepatocytes. In rat liver homogenates, higher concentrations (1 and 3 mM) of ascorbate suppressed lipid peroxide productions but lower concentrations (0.1 and 0.3 mM) did not. In contrast to the homogenate, ascorbate increased lipid peroxide production in liver slices in a concentration dependant manner. Iso-ascorbate, the epimer of ascorbate did not cause an increase the oxidative stress in liver slices. This differential effect between homogenates and liver slices implies that cellular integrity is required for ascorbate to induce oxidative stress. Wortmannin, an inhibitor of the GLUT (glucose transporter) thought to transport dehydroascorbate into cells, inhibited [14C]- ascorbate uptake and suppressed oxidative stress in liver slices. Wortmannin suppressed that [14C]- ascorbate uptake by GLUT following oxidation to [14C]dehydroascorbate. Taken together, these observations support our hypothesis that ascorbate is oxidized to dehydroascorbate by molecular oxygen in solution (i.e., plasma and culture medium) which is then carried into hepatocytes (via a GLUT) where it is reduced back to ascorbate causing oxidative stress.
Androstadienes/pharmacology ; Animals ; Ascorbic Acid/*metabolism/*pharmacology ; Biological Transport ; Edetic Acid/pharmacology ; Glutathione/*metabolism ; In Vitro ; Liver/*drug effects/*metabolism ; Male ; Oxidation-Reduction/drug effects ; Oxidative Stress/*drug effects ; Rats ; Rats, Sprague-Dawley ; Thiobarbituric Acid Reactive Substances/metabolism ; Time Factors

OBJECTIVETo compare the curative effects of primary osteoporosis treated with heat-sensitive point moxibustion and Gaitianli (Oyster Shell and Calcium Carbonate Chewable) tablets for oral administration and explore the treatment mechanism.

METHODSSixty cases of primary osteoporosis were randomly divided into a heat-sensitive point moxibustion group (moxibustion group) and a Gaitianli tablets group (medication group), 30 cases in each group. In the moxibustion group, the heat sensitized points were searched around Zusanli (ST 36), Pishu (BL 20), Shenshu (BL 23) and Mingmen (GV 4) and treated by heat-sensitive point moxibustion; in medication group, Gaitianli tablets were taken by oral administration, 3 pills for once and 3 times a day. The curative effects, bone mineral density (BMD), alkaline phosphatase (S-AKP) and urinary calcium to creatinine ratio (U-Ca/Cr) in both groups were observed before and after treatment.

RESULTSThe total effective rate was 86.7% (26/30) in moxibustion group, superior to that of 76.7% (23/30) in medication group (P < 0.05). After treatment, the BMD of lumbar vertebrae (L2-L4) mean was improved (P < 0.05), and the S-AKP and U-Ca/Cr were reduced (all P < 0.05); in medi cation group, the indexes above were no obvious changes (all P > 0.05).

CONCLUSIONThe therapeutic effect of primary osteoporosis treated with heat-sensitive point moxibustion is superior to that with Gaitianli tablets for oral administration. The mechanism is restraining bone resorption, increasing bone strength, keeping balance of bone metabolism, in order to increase bone mineral density and improve the clinical symptoms.

Acupuncture Points ; Aged ; Alkaline Phosphatase ; blood ; Bone Density ; Calcium ; urine ; Creatinine ; urine ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; methods ; Osteoporosis ; metabolism ; therapy