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Maternal diabetes is associated with an increased rate of congenital fetal anomaly. In the present study, diabetes was induced by streptozotocin in female rats one week prior to conception and the embryos were examined during organogenesis. Experimental diabetes is associated with over-production of free radicals and disturbed antioxidant defence, particularly in malformed embryos. Oxidative stress is demonstrated by increased MDA accumulation and reduced glutathione levels. Despite large differences in the reduced/oxidised glutathione ratios during organogenesis in the control, diabetic non-malformed and malformed embryo groups, the half-cell redox potential was constant for each group during the experimental period. Calculated redox potentials indicated that although embryo cells from the control and diabetic mother groups were of the same chronological age, the stages of development were different. Increased oxidative stress in rat embryos was associated with increased glutathione peroxidases and glutathione-S-transferase activity. This may, in part, provide an explanation for the observed accumulation of oxidised glutathione in malformed embryos. Moreover, decreased levels of vitamin C and selenium were observed. Increased oxidative stress and perturbations in antioxidant defence contribute to the high incidence of congenital anomalies in experimental diabetic gestation.

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The aim of the present study was to assess the therapeutic value of adding a high dose of vitamin E or an antioxidant combination to the treatment regimen of the rheumatoid disease. The study was carried out on 30 patients with rheumatoid disease diagnosed according to the criteria of American Rheumatism Association (ARA), subvided into three equal groups. Patients in group I received a standard treatment of intramuscular methotrexate (CAS 59-05-2; 12.5 mg/week), oral sulphasalazine (CAS 599-79-1; 0.5 g b.i.d.) and indometacin (CAS 53-86-1; 100 mg suppository at bed-time). In group II the patients received the standard treatment plus a combination of antioxidants. Patients in group III received a high dose of vitamin E (400 mg t.i.d.) in addition to the standard treatment. The disease state was evaluated using Ritchle's articular score index and the duration of morning stiffness. Laboratory evaluations included the rheumatoid factor, erythrocyte sedimentation rate (ESR), plasma levels of vitamin E and malonedialdehyde (MDA), and the activity of glutathione peroxidase (GPx). In the group receiving the standard regimen, the patients started to feel tangible improvement by the end of the second month. With adjuvant therapy of either the antioxidant combination or a high dose of vitamin E the symptoms of arthritis were better controlled from the first month. By the end of the second month, the values of the three monitoring tests were significantly decreased indicating better control of the disease. The percentage increase in the activity of GPx was highest in patients taking the antioxidant combination and least in those taking the standard treatment. The decrease in plasma MDA followed the same pattern. With adjuvant therapy, the vitamin E level in plasma increased with the duration of treatment. The results obtained in the present study are encouraging. The clinical improvement and the shift in the disease indices towards normal make the use of antioxidants as adjuvant therapy in rheumatoid disease worth pursuing.

Diabetic nephropathy (DN) is the most frequent cause of the end-stage renal disease (ESRD) in about 33% of diabetic patients. The present study aimed to explore the renoprotective effects of simvastatin (SV) and rosuvastatin (RSU) on the kidney of streptozotocin (STZ)-induced diabetic Sprague-Dawley (SD) rat model. As a result of induction of diabetes, serum [cystatin C, transforming growth factor-beta (TGF-β), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)] and tissue [interleukin 1 beta (IL-1β), interleukin 10 (IL-10), prostaglandin E2 (PGE2), cytochrome c, malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), GSH/GSSG ratio) markers showed significant increase than negative controls except tissue total glutathione (tGSH). Both SV and RSU significantly shifted the levels back toward near non-diabetic values. Both exerted the same renoprotective effect indicated by a significant decrease in cystatin C. However, SV significantly lowered IL-10, GSH/GSSG ratio, MDA, and 8-OHdG than RSU. Similarly, RSU significantly lowered cytochrome c and GSSG than SV. In conclusion, SV and RSU have differential renoprotective effects via alteration of growth factor, inflammatory, oxidative stress, DNA damage, and apoptotic signaling pathways.

Human schistosomiasis is a chronic and debilitating parasitic disease caused by parasitic trematode worms (schistosomes). Praziquantel (PZQ) is the drug of choice as it is active against all Schistosoma species, can be administered easily, has high cure and egg reduction rates, with no or only mild side effects. Rapid re-infection following treatment and the concerns about PZQ resistance has led to the search for new drugs to treat schistosomiasis. Significant progress has been made with artemisinin derivatives (e.g., artemether [ART]) that are used for chemoprophylaxis. This present study aims to look at the effects of ART and PZQ on the antioxidant defence of immature (three-week-old) and mature (six-week-old) stages of S. mansoni. The possible development of time- or concentration-dependent changes in oxidative stress is assessed by incubation with different sublethal drug concentrations (50, 75, 100 ng/mL for both ART and PZQ) and different time periods (one and three hours). The results indicated a time- and concentration-dependent depletion of glutathione (GSH), which was greater in the immature worms after incubation with ART. On addition of ART to the incubation medium of mature and immature worms, elevation in lipid peroxidation (TBARS) level was observed, which was time- and concentration-dependent, and more prominent in the immature schistosomes. Addition of PZQ to the incubation medium containing the immature schistosomes did not have a significant effect on TBARS level, except after three hours' incubation with the highest concentration used; however, a significant rise was seen in the mature worms. The PZQ had no effect on the activities of superoxide dismutase (SOD), glutathione peroxidase (tGPx, sGPx and nGPx) and glutathione transferase (GST) in mature or immature worms. While ART induced SOD activity in mature worms, it induced tGPx, nGPx and GST activities in a time- and concentration-dependent manner in both mature and immature worms. Activation was more prominent in the immature schistosomes. The results of the present study indicate that the immature schistosomes are more prone to oxidative killing, which probably participates in the mechanism of antischistosomal action of ART against the immature stage of S. mansoni. The results suggest that the mechanism of schistosomicidal action of PZQ is probably not substantially dependent on oxidative stress or oxidative killing.

The causes of, and predisposing conditions for, increased congenital anomalies in embryos of experimental diabetic gestation are not fully identified. In the present study, some possible factors involved in diabetes-induced embryopathy are explored. The concentration of PGE2, the gene expression of cyclooxygenases (COX-1 and COX-2) and level of apoptosis (measured by caspase-3 activity) are assessed during organogenesis in the embryos of streptozotocin-induced diabetic rats. The concentrations of PGE2 in the embryos of diabetic rats were lower than controls, with the lowest values in malformed embryos and their associated membranes (yolk sacs). The pattern of change in PGE2 was similar in the embryos of the control and diabetic groups, which showed a steady decline between days 9 and 11 of gestation. These changes in PGE2 were accompanied by a small decrease in COX-1 expression in all embryos and associated membranes during the same gestational period. Expression of COX-2, which was below normal in diabetic embryos, decreased between days 9 and 11 of gestation in all groups. In the membranes of non-malformed embryos, COX-2 expression peaked on day 10 of gestation. It was found that there was little or no detectable COX-2 expression in the membranes of malformed embryos on day 9 of gestation and although its expression was detectable on the following days it was much lower than in the other groups. Caspase-3 activity increased substantially between days 9 and 11 of gestation. Embryos from the experimentally diabetic group showed higher activity than did controls, with the largest increases in the malformed embryos. It would appear that COX-2 expression and PGE2 concentration (in both embryo and associated membranes) play a significant role in organ formation. The data presented here suggest that an unhealthy placenta may be instrumental in the development of malformed embryos.