Effects of 4-phenylbutyric acid on the development of diabetic retinopathy in diabetic rats: regulation of endoplasmic reticulum stress-oxidative activation.

There are good evidences suggesting that endoplasmic reticulum (ER) stress can be one of the contributing factors in the development of diabetic retinopathy. The present study was designed to investigate the effect of chemical chaperone 4-phenylbutyric acid (4-PBA) in alleviating the ER stress, and diabetic retinopathy in type 2 diabetic rats. Treatment of diabetic rats with 4-PBA, increased the antioxidant capacity, reduced the levels of lipid peroxidation, organised the state of apoptosis and regulated the ER stress - oxidative activation in retinal tissue. Also there was an improvement in the histological picture of retinal specimens compared to untreated diabetic rats. It was concluded that 4-PBA is a promising therapeutic agent for ER stress diseases such as diabetic retinopathy.

4-Phenylbutyric acid and rapamycin improved diabetic status in high fat diet/streptozotocin-induced type 2 diabetes through activation of autophagy.

An accumulating body of evidence supports the role of autophagy in the pathophysiology of T2DM. Also, abnormal endoplasmic reticulum (ER) stress response that has been implicated as a cause of insulin resistance (IR) could also be affected by the autophagic status in ß-cells. The present study was designed to investigate whether autophagy is regulated in T2DM as well as to investigate the modulatory effect of the ER stress inhibitor 4-phenylbutyric acid (4-PBA) and the autophagy inducer rapamycin (Rapa) on the autophagic and diabetic status using type 2 diabetic animal model with IR. Treatment of diabetic rats with either 4-PBA or Rapa improved significantly the states of hyperglycaemia and dyslipidaemia, increased the antioxidant capacity, reduced the levels of lipid peroxidation and ER stress and increased the autophagic flux. The obtained improvements were attributed mainly to the induction of autophagy with subsequent regulation of ER stress-oxidative activation and prevention of ß-cell apoptosis.

Radioprotective efficacy of Ginkgo biloba and Angelica archangelica extract against technetium-99m-sestamibi induced oxidative stress and lens injury in rats.

PURPOSE: Technetium-99m is a radioactive tracer that emits gamma rays. Its half-life time is 6 h. Similar to other ionizing radiations, the main mechanism of radiation-induced effects is initiated through the production of reactive oxygen species (ROS). This study was designed to determine the possible protective effects of Ginkgo biloba and Angelica archangelica against oxidative organ damage that was induced by 99mTc-sestamibi. MATERIALS AND METHODS: The experiments were performed on thirty-six Wistar-rats which were subdivided into control groups and groups exposed to 99mTc-sestamibi. The irradiated groups were either untreated or pre-treated with G. biloba or A. archangelica. For all groups, the levels and/or activities of Catalase (CAT), Glutathione (GSH), Malondialdehyde (MDA) and Superoxide-dismutase (SOD) were measured in blood and lenses. The soluble/insoluble protein ratio was determined and lens-protein profiles were obtained via Sodium-Dodecyl-Sulfate Polyacrylamide Gel-Electrophoresis (SDS-PAGE). RESULTS: There were no significant difference between the pre-treated and irradiated G. biloba group and control group, while both groups were significantly different (p < .05) from the untreated irradiated group. On the other hand, treatment with A. archangelica did not confer any significant protection against 99mTc-sestamibi induced toxicity. CONCLUSIONS: This study demonstrated that G. biloba, through its free radical scavenging and antioxidant properties, successfully attenuated 99mTc-sestamibi radiation-induced oxidative organ injury. The latter is a crucial factor of cataractogenesis in rats, suggesting that G. biloba may have a potential benefit in the protection against radiopharmaceuticals.

Ursodeoxycholic acid suppresses the formation of fructose/streptozotocin-induced diabetic cataract in rats.

The main objective of this study was to investigate the potential protective effect of ursodeoxycholic acid (UDCA) on fructose/streptozotocin-induced diabetic cataract in rats. The diabetic model (DM) was induced through the administration of 10% fructose in drinking water for 2 weeks followed by streptozotocin injection (intraperitoneal). One week later, hyperglycemia was assisted and diabetic animals were treated with UDCA either as local eye drops (0.5% solution, four times/day) or orally (100 mg/kg b.w.). Cataract formation was monitored biweekly and scored into four stages. After 12 weeks of treatment, rats were subjected to ophthalmological examination, and then, their blood and lenses were prepared for biochemical analysis of glucose, insulin, reduced glutathione, total antioxidant capacity, malondialdehyde, hydrogen peroxide, caspase-12, and lenticular total proteins. In addition, tertiary structure and conformational changes of lenticular soluble proteins were analyzed using SDS-PAGE and UV absorption while changes in lenticular α-crystallin structure were investigated using intrinsic tryptophan fluorescence. Results demonstrated that both local and oral UDCA restored the normal levels of lens T-AOC, MDA, H2 O2 , and caspase-12 and improved noticeably the levels of the lens GSH and total proteins. In addition, conformational and tertiary structure changes of soluble lens proteins were significantly reduced in UDCA-treated groups. Morphological examination of lenses revealed decreased score of cataract progression in UDCA-treated groups compared to DM animals. It was concluded that UDCA decreased the incidence of diabetic cataract by maintaining the antioxidant status, reducing the endoplasmic reticulum stress, and suppressing the structural changes of soluble lens proteins.