The protective effect of resveratrol on diazinon-induced oxidative stress and glucose hemostasis disorder in rats' liver.

This study was intended to assess the possible protective effect of resveratrol (Res) against oxidative stress and glucose hemostasis disorder in rats exposed to diazinon (DZN) for 4 weeks. Totally 25 Sprague-Dawley rats were divided randomly into five groups: Control (orally received corn oil), DZN group (orally received 70 mg/kg/day), and Res groups (received DZN 70 mg/kg/day plus Res doses of 5, 10, and 20 mg/kg bodyweight/-day), respectively. DZN significantly inhibited serum acetylcholinesterase enzyme (Ach E), serum and liver catalase, glutathione peroxidase activities, also total antioxidant capacities. On the other hand, DZN increased serum and liver malondialdehyde. DZN significantly increased Forkhead box protein O1 (Foxo1) expression and decreased phosphatase and tensin homolog (PTEN) and sirtuin 1 (Sirt-1) expression. DZN impaired glucose hemostasis. Instead, Res treatment significantly reversed status of oxidative stress and antioxidant enzymes activities induced by DZN. Also, Res improved glucose hemostasis. Res increased PTEN and Sirt-1 expression and reduced Foxo1 expression. Res administration ameliorated liver histopathological changes induced by DZN. These data confirmed that DZN significantly enhances oxidative stress and impairs glucose hemostasis. While Res showed a protective effect against the toxicity induced by DZN in rats.

Eudragit L-100 Capsules Aromatize and Quaternerize Chitosan for Insulin Nanoparticle Oral Delivery During Toxic Oxidative Stress in Rat Liver and Kidney.

BACKGROUND: Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that is considered as a low permeable and unstable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolyze amide-bonds between various amino-acids in the structures of peptides and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery, and for the development of an oral delivery system, some obstacles in oral administration of peptides and proteins including low permeability and low stability of the proteins in GI should be overcome. OBJECTIVE: In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. METHODS: INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs were filled in pre-clinical capsules, and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30 U/kg/day, orally), group 4: the diabetic rats received regular insulin (5 U/kg/day, subcutaneously). At the end of the treatment, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining . RESULTS: Biochemical parameters, and liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with the diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. CONCLUSION: Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs appears to be safe. Lay Summary: Although oral route is the most preferred route of administration, but oral delivery of peptides and proteins is still a challenging issue. Diabetes Mellitus may lead to severe complications, which most of them are life-threatening. In this study, we are testing the toxicity of oral insulin nanoparticles in kidney and liver of rats. For this investigation, we will prepare insulin nanoparticles composed of a quaternized derivative of chitosan. The nanoparticles will be administered orally to rats and the level of oxidative stress in their liver and kidney will be determined. The data will be compared to the subcutaneous injection of insulin.