Aldehyde reductase (AKR1A) plays a role in the biosynthesis of ascorbic acid (AsA), and AKR1A-deficient mice produce about 10-15% of the AsA that is produced by wild-type mice. We found that acetaminophen (AAP) hepatotoxicity was aggravated in AKR1A-deficient mice. The pre-administration of AsA in the drinking water markedly ameliorated the AAP hepatotoxicity in the AKR1A-deficient mice. Treatment of the mice with AAP decreased both glutathione and AsA levels in the liver in the early phase after AAP administration, and an AsA deficiency delayed the recovery of the glutathione content in the healing phase. While in cysteine supply systems; a neutral amino acid transporter ASCT1, a cystine transporter xCT, enzymes for the transsulfuration pathway, and autophagy markers, were all elevated in the liver as the result of the AAP treatment, the AsA deficiency suppressed their induction. Thus, AsA appeared to exert a protective effect against AAP hepatotoxicity by ameliorating the supply of cysteine that is available for glutathione synthesis as a whole. Because some drugs produce reactive oxygen species, resulting in the consumption of glutathione during the metabolic process, the intake of sufficient amounts of AsA would be beneficial for protecting against the hepatic damage caused by such drugs.

Migraine is a painful condition in which patients suffer from recurrent episodes of disabling pain, which could be very severe and can lead to grave psychological disturbances. There is no curative treatment for migraine, but there are various treatment modalities, though, with conflicting reports on their efficacy. This study was conducted to compare the effectiveness of electro acupuncture therapy and the conventional drug therapy on the psychological profile of migraneurs based on the assessment of quality of life and disability parameters. Migraneurs (n = 60) were recruited from the Psychiatry and Neurology OPD, Guru Tegh Bahadur Hospital, Delhi. Following a written consent, migraneurs were randomly allocated into 2 study groups--Group A received 10 sittings of electro acupuncture on selected acupuncture points over a period of 30 days, while for the same duration the Group D received a conventional drug therapy in the form of oral flunarizine 20 mg OD along with paracetamol 500 mg SOS. The patients were assessed twice, before and after completion of the treatment programme (30 days). The quality of life was assessed with WHOQOL BREF (WHO Quality of Life Biomedical Research and Education Foundation) questionnaire and the disability was assessed with MIDAS (Migraine Disability Assessment) questionnaire. Statistical analysis was performed using repeated measure's ANOVA with Tukey's test. Migraneurs were found to have lower quality of life and higher disability scores but following the treatment regimes, the 2 study groups showed a significant improvement in both the parameters studied. It was however observed, that the acupuncture group showed a better response and was thus found to be more effective as compared to the drug group (P = 0.005 to 0.000). We thus conclude that acupuncture is a better treatment option than the conventional drug therapy in not only relieving the pain of migraine but in also improving the psychological profile in migraneurs. Hence its use should be encouraged as an alternative/adjunct treatment for migraine.

BACKGROUND:The aim of the present study was to determine the therapeutic effects of medical ozone therapy on acute acetaminophen (APAP)-induced hepatotoxicity which were not clearly demonstrated in prior studies.

METHOD:Twenty-four mice were randomly assigned into three equal groups: Group 1 (control), Group 2 (APAP) and Group 3 (APAP +ozone). Hepatotoxicity was induced by APAP given as a single dose of 300 mg/kg intraperitoneally in Groups 2 and 3. Additionally, Group 3 received 20 mcg/0.5 mL ozone intraperitoneal twice a day for the remaining of the study. Other groups received saline injections. On the fourth day of the study, biochemical variables (AST, ALT, ALP) and liver histopathology wasassessed.

RESULTS:Intraperitoneal administration of a single dose of APAP induced hepatocellular damage that was shown by both liver enzymes and histopathological changes (p < 0.001). AST, ALT, ALP levels were elevated in both groups 2 and 3 and the difference from group 1 was statistically significant (p < 0.01).Mean ALT and AST levels of group 2 were statistically significantly higher versus group 3 (p < 0.01). In histopathological examinations; necrosis and inflammation were more prominent in Group 2 compared to Group 3 (p < 0.01).

CONCLUSION:Ozone showed beneficial effects on APAP hepatotoxicity at a statistically significant level. It is known that ozone has therapeutic effects in various diseases owing to its antioxidant effects. The present study suggests that ozone may be utilized as a routine supplementary therapy in acute APAP hepatotoxicity.

BACKGROUND:Oxidative stress and inflammation are involved in the pathogenesis of paracetamol-induced renal damage. This study examines the relationship between 8-iso-prostaglandin F2α (8-iso-PGF2α) and platelet activation as well as the relative contribution of the pro-inflammatory markers interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) in enhanced 8-iso-PGF2α biosynthesis, as a complementary onset during analgesic nephropathy induced by chronic treatment with paracetamol. The protective effects of vitamin C on the aforementioned settings are also investigated.

METHODS:Analgesic nephropathy was induced in Wistar rats. Renal function markers and the activity of antioxidant enzymes were determined spectrophotometrically. Immunoassays were used to measure the pro-inflammatory markers and the markers of lipid peroxidation and platelet activation.

RESULTS:The chronic treatment with paracetamol led to renal dysfunction, represented by the elevation of plasma urea and creatinine and the decline in the enzymatic antioxidant status, but did not cause a significant increase in TNF-α and IL-1β. The paracetamol-induced lipid peroxidation and enhanced production of 8-iso-PGF2α was not sufficient to cause changes in platelet activation represented by the level of 11-dehydro thromboxane B2.

CONCLUSIONS:Our results suggest that oxidative stress cannot circumvent the need of stimulation by circulatory cytokines in order to induce inflammatory response and changes in platelet activation during analgesic nephropathy. Vitamin C proved to be beneficial in restoring the renal function markers to normal, increasing the renal enzymatic antioxidant potential, inhibiting lipid peroxidation, and lowering cytokine production and 11-dehydro thromboxane B2 excretion. The observed effects of vitamin C offer support for its potential use as protective treatment in cases of chronic paracetamol overdose.