Atef T. Fahim

Oxidative stress in systemic lupus erythematosus and rheumatoid arthritis patients: relationship to disease manifestations and activity

Aim:  The present work was undertaken to study the status and contribution of oxidative stress in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients. Relationship of the markers of oxidative stress to clinical manifestations, disease activity, damage and medications used were well considered.

Effect of pumpkin-seed oil on the level of free radical scavengers induced during adjuvant-arthritis in rats

Pumpkin-seed oil (PSO), a natural supplement rich with antioxidant ingredients, was given to rats in which arthritis was induced using Freunds complete adjuvant. Its effect was compared with that of indomethacin, as a classical anti-inflammatory agent. Two experimental patterns were studied, an acute phase that was applied only with PSO and a chronic phase applied for both PSO and indomethacin. Compared to normal untreated rats, it was shown that the induction of arthritis caused a decrease in serum sulphhydryl groups, with an increase in serum ceruloplasmin in both phases. Blood glutathione was first elevated in the acute phase, then its level was reduced in the chronic phase. Serum N-acetyl-beta-D-glucosaminidase activity was elevated only at the acute phase, while plasma total proteins and albumin were reduced at the chronic phase. Liver glucose-6-phosphate dehydrogenase activity was markedly increased, while no changes were observed in the levels of liver lipid peroxides and glutathione. These changes in the studied parameters were attributed to the superoxides and free radicals during arthritic inflammation. Administration of PSO succeeded in modulating most of the altered parameters affected during arthritis, especially at the chronic phase. Also, a remarkable inhibition of paw oedema was observed. A similar pattern was obtained upon treatment with indomethacin except that indomethacin markedly elevated liver lipid peroxides levels. Concurrent administration of PSO with indomethacin caused no changes in the parameters studied compared to that induced by treatment with indomethacin alone.

Resveratrol and curcumin ameliorate di-(2-ethylhexyl) phthalate induced testicular injury in rats.

The present study aimed to evaluate the protective role of resveratrol and curcumin on oxidative testicular damage induced by di-(2-ethylhexyl) phthalate (DEHP). Male Wistar rats were divided into six groups; three groups received oral daily doses of DEHP (2g/kgBW) for 45days to induce testicular injury. Two of these groups received either resveratrol (80mg/kgBW) or curcumin (200mg/kgBW) orally for 30days before and 45days after DEHP administration. A vehicle-treated control group was also included. Another two groups of rats received either resveratrol or curcumin alone. Oxidative damage was observed by decreased levels of total antioxidant capacity (TAC) and glutathione (GSH) and increased malondialdehyde (MDA) level in the testes of DEHP-administered rats. Serum testosterone level as well as testicular marker enzymes activities; acid and alkaline phosphatases (ACP and ALP) and lactate dehydrogenase (LDH) showed severe declines. DEHP administration caused significant increases in the testicular gene expression levels of Nrf2, HO-1, HSP60, HSP70 and HSP90 as well as a significant decrease in c-Kit protein when compared with the control group. Histopathological observations provided evidence for the biochemical and molecular analysis. These DEHP-induced pathological alterations were attenuated by pretreatment with resveratrol and curcumin. We conclude that DEHP-induced injuries in biochemical, molecular and histological structure of testis were recovered by pretreatment with resveratrol and curcumin. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties along with boosting Nrf2, HSP 60, HSP 70 and HSP 90 gene expression levels and as such may be useful potential tools in combating DEHP-induced testicular dysfunction.

Effect of praziquantel on some aspects of carbohydrate metabolism in mice infected with Schistosoma mansoni

Schistosoma mansoni infection in mice resulted in a marked decrease in blood glucose and liver glycogen accompanied by a significant increase in hepatic glucose-6-phosphatase (G-6-Pase) activity. Moreover, the results indicated that infection produced a significant increase in blood pyruvate and hepatic glucose-6-phosphate dehydrogenase (G-6-PD) activity with a significant decrease in blood lactate. Infected mice were treated with praziquantel which was given at two doses of 500 mg/kg body wt on two consecutive days. Seven and 14 days respectively after drug administration, such treatment caused a marked improvement in the previous aspects of carbohydrate metabolism. This is indicated by the tendency of the blood glucose of infected mice to be restored, the marked increase in their liver glycogen content, the normalization of their blood lactate and pyruvate as well as by the marked decrease of their hepatic G-6-Pase activity and the progressive increase in their hepatic G-6-PD activity. Praziquantel given to normal mice moderately affected the blood glucose and the previously mentioned hepatic enzymes. However, the drug markedly increased the liver glycogen content of normal mice and failed to elicit any change in their blood pyruvate and lactate. Possible explanations of these findings are discussed.

Insulin-like growth factor system in Egyptian children with acute lymphoblastic leukemia.

Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) have been reported to play an important role in tumor proliferation. This study aimed to investigate the validity of measuring IGFs and specific IGFBPs in the serum of Egyptian children with acute lymphoblastic leukemia (ALL) as additional markers in diagnosis and follow-up of the disease. IGF-I, IGF-II, IGFBP-2, and IGFBP-3 were determined in the sera of 33 ALL patients at time of diagnosis and after an intensification phase of chemotherapy (IPC) that lasts about 6 months as well as in 15 healthy children as a control group using enzyme-linked immunosorbent assay (ELISA) technique. At time of diagnosis, serum IGF-I, IGF-II, and IGFBP-3 were significantly lower than those in the control group. After IPC, serum IGF-I and IGF-II returned to their normal levels, while serum IGFBP-3 was still decreased. On the other hand, serum IGFBP-2 was significantly higher than those in the control group at diagnosis, but returned to normal value after IPC. In conclusion, the changes in IGF system could be useful to support diagnosis and follow-up of children with ALL.

Resveratrol and dimethyl fumarate ameliorate depression-like behaviour in a rat model of chronic unpredictable mild stress

Chronic stress occurs in everyday life and induces depression. Emerging evidence shows that oxidative stress, inflammation and apoptosis are main contributing pathophysiologic mechanisms of depression. Resveratrol and dimethyl fumarate (DMF) are natural antioxidants that have diverse biological activities. Our study aimed to determine whether resveratrol and DMF affected these systems in rats exposed to chronic unpredictable mild stress (CUMS)-induced depression-like behaviours. Rats were submitted to 8 weeks of CUMS to induce depressive-like behaviour. The depressive-like behaviour of rats induced by CUMS was revealed by an elevated serum corticosterone level and decreased serum and hippocampal serotonin levels. Our results showed that CUMS significantly-induced behavioural abnormalities (reduced sucrose preference and increased immobility time) in stressed rats. CUMS exposure significantly decreased BDNF and β-catenin expression levels as well as increased GSK-3β expression level in hippocampus. Furthermore, CUMS exposure resulted in a significant increase in expression levels of NF-κB, TNF-α and IL-Iβ accompanied by decreased Bcl-2 expression level. CUMS increased hippocampal MDA level and significantly decreased hippocampal GSH and serum total antioxidant capacity levels compared to the control group. Histopathological examinations provided evidence for the biochemical and molecular analysis. All of these effects were significantly ameliorated by administration of resveratrol and DMF. In conclusion, our study revealed that resveratrol and DMF exerted promising antidepressant-like effects in CUMS rats that are mediated in part by suppressing the neuroinflammation, oxidative stress, apoptosis and up-regulating hippocampal BDNF and β-catenin levels. Serum serotonin analysis may be a reliable indicator for monitoring depression.