Resveratrol prevents liver fibrosis via two possible pathways: Modulation of alpha fetoprotein transcriptional levels and normalization of protein kinase C responses.

OBJECTIVE: Liver fibrosis is a global health problem that causes approximately 1.4 million deaths per year. It is associated with inflammation, oxidative stress, necrosis and ends with cirrhosis, liver cancer, or liver failure. Therefore, the present study was constructed to investigate the protective effect of resveratrol (RVT) on liver fibrosis, focusing on the possible involvement of alpha 1-fetoprotein and protein kinase C signaling. MATERIALS AND METHODS: Rats received thioacetamide (TAA) (200 mg/kg, intraperitoneal) twice weekly, for 4 successive weeks to induce liver fibrosis. RVT (30 mg/kg, per os) and vehicle were administered orally for 1 month before and another month during TAA intoxication. Body weights and mortality rate were assessed during the experiment. Liver functions and protein concentration were determined in serum, while liver tissues were analyzed for oxidative and fibrotic biomarkers. Moreover, histological examinations were performed to liver biopsies. RESULTS: RVT prevented the debility of TAA; liver functions including alanine aminotransferase, aspartate aminotransferase, bilirubin, and albumin were also protected. RVT prevented TAA oxidative stress, and normal liver contents of malondialdehyde and reduced glutathione were markedly preserved. In addition, RVT abolished the stimulant effect of TAA to fibrosis markers and conserved normal liver contents of nuclear factor kappa B, hydroxyproline, and alpha fetoprotein. Histological examinations indicated normal liver architecture in RVT-administered rats as compared to their TAA-administered peers. CONCLUSION: RVT was able to enhance liver functions, prevent oxidative stress, and eliminate liver fibrosis. Hence, the present data highlight the therapeutic potential of RVT as a protective agent against liver fibrosis.

Subclinical reduced G6PD activity in rheumatoid arthritis and Sjögren's Syndrome patients: relation to clinical characteristics, disease activity and metabolic syndrome.

OBJECTIVE: Glucose-6-phosphate dehydrogenase (G6PD) is an important site of metabolic control in the pentose phosphate pathway. The purpose of this study was to investigate the enzyme activity of G6PD in Rheumatoid Arthritis (RA) and Sjögren's Syndrome (SS) patients not known to be deficient in this enzyme. It was also within the scope of the aim to find the relation of G6PD to the presence of metabolic syndrome (MetS) in these patients. METHODS: Erythrocyte G6PD activity was evaluated in 40 RA patients, 30 SS patients and in 30 age- and sex-matched control. The clinical characteristics, disease activity score (DAS28), SS disease activity (SSDAI) and damage (SSDDI) indices and presence of MetS of the included patients were analyzed in relation to the enzyme level. RESULTS: The G6PD activity in RA patients (7.72 ± 3.57 U/g Hb) was significantly reduced compared to that in the SS patients (11.55 ± 3.14 U/g Hb) and control (13.23 ± 3.34 U/g Hb) especially those with MetS (4.61 ± 1.84 U/g Hb) (p < 0.001). There was a significant negative correlation of the G6PD activity with the disease duration and DAS28 (p < 0.001). CONCLUSION: The results of this study, suggest that G6PD not only does not protect against MetS in RA, but may even be considered a risk factor for the development of this disorder. The identification of regulatory tools for G6PD activity may prove promising for treating the associated metabolic disorders and chronic inflammation in RA.

Protective effects of combined therapy of gliclazide with curcumin in experimental diabetic neuropathy in rats.

Diabetic neuropathy is the most common chronic complication of diabetes. The aim of the present study was to evaluate the protective effects of curcumin against neuropathy in gliclazide-treated diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (45 mg/kg). Diabetic animals were given gliclazide (10 mg/kg, orally) alone or combined with curcumin (100 mg/kg, orally) or gabapentin (30 mg/kg, intraperitoneally as a positive control). Behavioral responses to thermal (hot plate and tail flick) and mechanical (tail pinch) pain, and some biochemical tests (serum glucose, C-peptide, peroxynitrite, lipid peroxides, and tumor necrosis factor-α) were assessed after 5 consecutive weeks of daily treatment. Combined treatment of curcumin with gliclazide significantly increased hot-plate and tail-flick latencies in comparison with that of the diabetic control group. The threshold of mechanical hyperalgesia was also significantly elevated. Serum glucose and C-peptide levels were significantly increased in the combined treatment compared with the diabetic control group, whereas serum levels of peroxynitrite, lipid peroxide, and tumor necrosis factor-α production were significantly decreased. The data suggest that the combination of curcumin with gliclazide may protect against the development of diabetic neuropathy, with favorable effects with respect to the gliclazide/gabapentin combination.