Evaluation of acrylamide exposure in pregnant Wistar rats as a risk of developing renal disease in their litters.

This study was designed at evaluating the acrylamide (ACR) exposure in pregnant Wistar rats as a risk of developing renal disease in their litters. Four groups of pregnant female rats were used. Group 1 control animals were given 2 ml/kg/day of distilled water. Groups 2, 3, and 4 animals were given oral gavage doses of 2, 5, and 10 mg/kg/day of ACR respectively immediately pregnancy was confirmed. Mother rats were sacrificed 10 weeks after delivery and litters were sacrificed at 13 weeks. Proteinuria was observed in ACR-treated mother rats and their litters. Serum electrolytes, urea, and creatinine values observed in the treated group were deranged for both the mothers and litters respectively. Disruption of nephrogenesis was observed in the litters of ACR-treated mother compared to the control. The results of the effect of ACR on lipid profile indicated a significant elevation in the LDL, cholesterol, and triglyceride compared to the control. There was significant reduction in the SOD, catalase, GSH, and significant elevation in the C-reactive protein and malondialdehyde. Conclusively, exposure to acrylamide during pregnancy is a risk factor for the development of renal disease in the mother rats and their litters.

The antitumor activity of hydrophobin SC3, a fungal protein.

The use of mushroom extracts has been common practice in traditional medicine for centuries, including the treatment of cancer. Proteins called hydrophobins are very abundant in mushrooms. Here, it was examined whether they have antitumor activity. Hydrophobin SC3 of Schizophyllum commune was injected daily intraperitoneally starting 1 day after tumor induction in two tumor mouse models (sarcoma and melanoma). SC3 reduced the size and weight of the melanoma significantly, but the sarcoma seemed not affected. However, microscopic analysis of the tumors 12 days after induction revealed a strong antitumor effect of SC3 on both tumors. The mitotic activity of the tumor decreased 1.6- (melanoma) to 2.3-fold (sarcoma), while the vital mass decreased 2.3- (melanoma) to 4.3-fold (sarcoma) compared to the control. Treatment did not cause any signs of toxicity. Behavior, animal growth, and weight of organs were similar to animals injected with vehicle, and no histological abnormalities were found in the organs. In vitro cell culture studies revealed no direct cytotoxic effect of SC3 towards sarcoma cells, while cytotoxic activity was observed towards melanoma cells at a high SC3 concentration. Daily treatment with SC3 did not result in detectable levels of anti-SC3 antibodies in the plasma. Instead, a cellular immune response was observed. Incubation of spleen cells with SC3 resulted in a 1.5- to 2.5-fold increase in interleukin-10 and TNF-α mRNA levels. In conclusion, the nontoxic fungal hydrophobin SC3 showed tumor-suppressive activity possibly via immunomodulation and may be of benefit as adjuvant in combination with chemotherapy and radiation.

Oral and pulmonary delivery of thioether-bridged angiotensin-(1-7).

Instability and proteolytic degradation limit the delivery options and in vivo efficacy of many therapeutic peptides. We previously generated a thioether stabilized angiotensin-(1-7) analog, cAng-(1-7), which is resistant against proteolytic degradation in the circulation. We here investigated oral and pulmonary delivery of this compound. In a first step we investigated the in vitro stability of the peptide under conditions that mimic those that will be met after oral administration. We demonstrated that cAng-(1-7) is stable at pH 2.0, a pH value close to that of the stomach, has enhanced resistance to breakdown by proteases from pancreas at pH 7.4, and is resistant to breakdown by proteases from liver at the lysosomal pH 5.0. We subsequently demonstrated that, in the absence of any delivery system or formulation, cAng-(1-7) can be delivered orally and via the lung, with bioavailabilities of 0.28+/-0.05% and 28+/-5%, whereas drug uptake was maximal after subcutaneous administration (bioavailability of 98+/-6%). Therapeutic concentrations could be reached via all three routes of administration. The data prove that introduction of a thioether bridge in peptides opens novel delivery options for medically important peptides.