Mohamed-Ahdy Saad

Schistosoma mansoni nephropathy in Syrian golden hamsters : effect of dose and duration of infection

In this work, 180 golden hamsters were infected with Schistosoma mansoni and 30 hamsters matched for age and sex served as controls. According to the number of injected cercariae, infected hamsters were divided into six main groups (20, 50, 100, 150, 200 and 250 cercariae). Each group was divided into five subgroups, according to the duration of infection after which animals were sacrificed (4, 6, 8, 12 and 24 weeks). Control and infected hamsters were subjected to laboratory evaluations (serum creatinine, blood urea nitrogen, cholesterol, albumin, total protein and urine protein concentration) and histopathologic examinations of kidney and liver tissues. A significant proteinuria, hypoalbuminemia and hypercholesterolemia was observed in schistosome infected (50 cercariae or more) but not in the controls and the group infected with 20 cercariae. There was significant correlation between these changes and duration of infection and the number of adult worm recovered from the mesenteric circulation at the end of the experiments. Histopathologic evaluation showed appearance of the circulating schistosome antigens, circulating anodic antigen (CAA) and circulating cathodic antigen (CCA), and of IgG glomerular deposits by the 6th week following infection; mesangial hypercellularity appeared early after infection (6-8 weeks), renal amyloid deposition appeared later (8-12 weeks). Egg antigens were not detected in the renal glomeruli. There was a significant correlation between the pathologic changes and duration of infection and the number of recovered adult worms from the mesenteric circulation. No histopathologic lesions were detected in controls and the group injected with 20 cercariae. A significant correlation was found between hepatic periportal fibrosis, amyloidosis and immune complex, deposition in the renal glomeruli. Hamsters did not tolerate infection with 150 cercariae or more for more than 12 weeks, and 20 cercariae caused no detectable glomerular disease. From this study, we concluded that S. mansoni infection causes nephropathy in the Syrian golden hamster. The disease became biochemically and histopathologically manifest by the 6th week following infection. Both immune complex deposition and renal amyloidosis stand as major pathogenic mechanisms. CAA and CCA are the major responsible antigens. Hepatic disease has an impact on the kidney lesion. 50 cercariae are the best dose to produce disease without early death of the animal. There is a significant correlation between the kidney disease and the duration and the load of S. mansoni infection.

Study of the Effect of Route of Administration of Mesenchymal Stem Cells on Cisplatin-Induced Acute Kidney Injury in Sprague Dawley Rats.

Background and Objectives Mesenchymal stem cells (MSCs) have been shown to ameliorate cisplatin-induced acute kidney injury (AKI). The present study compares the efficacy of different routes of MSCs administration on kidney damage and regeneration after cisplatin-induced AKI. Methods A single intraperitoneal injection of cisplatin (5 mg/kg) was used to induce AKI in 160 rats. MSCs (5×106) were given by either intravenous, intra-arterial or kidney sub capsular injection one day after cisplatin injection. Suitable control groups were included. Rats were sacrificed at 4, 7, 11 and 30 days after cisplatin injection. Kidney function parameters, kidney tissue oxidative stress markers, and scoring for renal tissue injury, regeneration and chronicity were all determined. Results MSCs by any routes were able to ameliorate kidney function deterioration and renal tissue damage induced by cisplatin. The overall results of the three routes were equal. Differences between the different routes in one parameter were transient and inconsistent with other parameters. Conclusions Changing the route of MSCs injection does not have a major influence on the outcome. Future evaluation should focus on differences between the routes of administration considering the long term safety.

Amniotic Fluid-Derived Mesenchymal Stem Cells Cut Short the Acuteness of Cisplatin-Induced Nephrotoxicity in Sprague-Dawley Rats.

Background and objectives Cisplatin is a nephrotoxic chemotherapeutic agent. So, preventive measures worth to be evaluated. Human amniotic fluid stem cells (hAFSCs) in prevention or amelioration of cisplatin-induced acute kidney injury (AKI) in Sprague-Dawley rates have been tested. Methods 80 Sprague-Dawley rats (250~300 g) were used and divided into 4 major groups, 20 rats each. Group I: Saline-injected group. Group II: Cisplatin-injected group (5 mg/kg I.P). Group III: Cisplatin-injected and hAFSCs-treated group (5×106 hAFSCs I.V. one day after cisplatin administration). Group IV: Cisplatin-injected and culture media-treated group. Each major group was further divided into 4 equal subgroups according to the timing of sacrifice; 4, 7, 11 and 30 days post-cisplatin injection. Renal function tests were done. Kidney tissue homogenate oxidative stress parameters malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were determined. Histopathological scoring systems for active injury, regenerative and chronic changes were analyzed separately. Results hAFSCs characterization and differentiation was proved. Cisplatin injection resulted in a significant increase in serum creatinine and MDA and decrease in SOD, GSH and creatinine clearance. These changes were attenuated early by day 4 with the use of hAFSCs. Cisplatin injection induced tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. The use of hAFSCs was associated with significantly lowered injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4. Conclusion hAFSCs have both a protective and regenerative activities largely through an antioxidant activity. This activity cut short the acuteness of cisplatin nephrotoxicity.

Comparison of lactate and β-hydroxybutyrate in the treatment of concanavalin-A induced hepatitis

&NA; Simple metabolites released during physical exercise and fasting like lactate (Lac) and &bgr;‐hydroxybutyrate (BHB) have recently been shown to possess anti‐inflammatory properties. However, the effects of these metabolites in immune mediated hepatitis are still unknown. Accordingly, we investigated the role of Lac, BHB and their combination on experimentally induced hepatic inflammation. Adult male mice were administered concanavalin A (Con A, 15 mg/kg, intravenous) for 12 h. In the treatment groups, mice were treated 1 h after Con A‐intoxication with Lac (500 mg/kg, intraperitoneal), BHB (300 mg/kg, intraperitoneal) and their combination. The results demonstrated that Lac and BHB, especially when combined together, alleviated Con A‐induced hepatocellular injury (ALT, AST and LDH) and necrosis (hematoxylin‐eosin and electron microscopy). These beneficial effects correlated with attenuating Con A‐induced elevation in hepatic oxidative stress parameters (MDA and NOx). Mechanistically, administration of Lac and BHB led to inhibition of Con A‐induced phosphorylation of JNK and AMPK proteins in the liver to the same extent. These effects were concordant with curbing Con A‐mediated overexpression of the pro‐inflammatory cytokines TNF‐&agr;, IL‐6 and IL‐12 and activation of the transcription factor NF‐&kgr;B. The marked anti‐inflammatory properties of combining Lac and BHB were attributed to their cooperation in repressing immune cells (monocytes and neutrophils) infiltration to the liver. Unlike BHB, Lac administration markedly induced the reparative STAT3 and ERK phosphorylation in the livers of Con A‐intoxicated mice at the early time point. In conclusion, the simultaneous use of Lac and BHB might be an auspicious strategy for limiting immune mediated hepatitis. Graphical abstract: Figure. No caption available. HighlightsLac and BHB abated Con A‐liver injury and overproduction of inflammatory cytokines.Lac and BHB limited inflammatory cells infiltration to the liver due to Con A challenge.Lac and BHB inhibited Con A‐induced phosphorylation of JNK and AMPK proteins.Lac and BHB enhanced Con A‐induced phosphorylation of STAT3 and ERK proteins.