Ifosfamide (IFO) is a highly effective chemotherapeutic agent for treating a variety of pediatric solid tumors. However, its use is limited due to its serious side effect on kidneys. The side-chain oxidation of IFO in renal tubular cells produces a reactive toxic metabolite that is believed to be responsible for its nephrotoxic effect. Therefore, this study was carried out to investigate the possible underlying mechanisms that may be involved in IFO-induced nephrotoxicity, including free radical generation and the possible role of alpha lipoic acid (ALA) versus N-acetylcysteine (NAC) in protection against this toxicity. Male albino rats were injected intraperitoneally with saline, IFO (50 mg/kg daily for 5 days), IFO + ALA (100 mg/kg daily for 8 days) and IFO + NAC (200 mg/kg daily for 8 days). Kidney malondialdehyde, nitric oxide and glutathione contents and serum biochemical parameters and histopathological analysis were determined. Both ALA and NAC markedly reduced the severity of renal dysfunction induced by IFO. NAC was more nephroprotective than ALA. This study suggests that oxidative stress is possibly involved in the IFO-induced nephrotoxicity in rats. The study also suggests the potential therapeutic role for ALA and NAC against IFO-induced nephrotoxicity.

Cytokines and nitric oxide (NO) are involved in the pathogenesis of autoimmune diabetes mellitus (DM). Rosiglitazone is an insulin-sensitizing drug that is a ligand for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR-gamma). The anti-inflammatory and immunomodulating properties of PPAR-gamma have been documented. The aim of this study is to investigate the effectiveness of rosiglitazone in autoimmune DM and to clarify the possible mechanism(s) involved. Autoimmune DM was induced in adult male Balb/c mice by co-administration of cyclosporin A and multiple low doses of streptozotocin. Diabetic mice were treated daily with rosiglitazone (7 mg/kg, p.o.) for 21 days. Blood glucose level (BGL), serum insulin level and pancreatic levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and NO were measured. Histopathological examination and immunohistochemical determination of CD4 and CD8 T lymphocytes in the pancreatic islets were performed. In addition, analysis of pancreatic protein expression was carried out. The results showed that rosiglitazone treatment resulted in a significant decrease in the BGL and the pancreatic levels of TNF-alpha, IFN-gamma and NO compared to diabetic mice. The serum insulin level was significantly increased after rosiglitazone treatment compared to diabetic mice. The destroyed pancreatic islets were regenerated and became free from both CD4 and CD8 T cells after treatment. Furthermore, many changes in pancreatic protein expression were observed. These results suggest that rosiglitazone has a beneficial effect in the treatment of autoimmune diabetes, an effect that seemed to be a secondary consequence of its anti-inflammatory and immunomodulating properties and might be reflected at the level of protein expression.

Introduction: Injuries and violence represent a major public health problem worldwide. It is still a leading cause of mortality specially in developing countries. Ubiquitin is a heat shock protein, which is induced by various kinds of traumatic stress. Aim of the work: The aim of this study is to investigate the immunohistochemical expression of ubiquitin in suprarenal and renal tissues in blunt and sharp traumatic deaths. Subjects and methods: Cross sectional post-mortem study was conducted on the traumatic medicoegal autopsy cases and natural cases in Banha medicolegal unit (Ministry of Justice) over six months interval from February 2016 to August 2016. For all medicolegal cases, the data collection sheet included age, sex, date of death, survival time and cause of death. Histological examinations and ubiquitin immunostaining were performed on the suprarenal and renal tissues. Results: Forty-five autopsy cases were included in this study. The majority of victims were males (84.4%) from rural regions (70.5%). Blunt injuries represented the majority of traumatic deaths (57.14%). The greater part of traumatic cases (74.3%) died within 24 hours post injuries. Traumatic cases revealed acute tubular necrosis and vascular degeneration in renal tissue and exhaustion of lipid contents of zona fasiculata in suprarenal tissue specimens. Traumatic deaths showed significant increase in ubiquitin expression in compared to natural deaths in renal distal convoluted tubules and suprarenal cortex. Moreover, there was significant positive correlation between survival period and positive ubiquitin immune expression in each of renal distal convoluted tubules (r=0.461, p=0.005) and suprarenal cortex (r=0.459, p=0.006). Conclusion: Ubiquitin immunoexpression can serve as a stress indicator of traumatic deaths and it may be useful for determination of survival period.