Peroxisome proliferator-activated receptor-γ doesn't modify altered electrophysiological properties of the CA1 pyramidal neurons in a rat model of hepatic cirrhosis.

Regarding the low quality of life due to the cognitive complications in the patients with hepatic cirrhosis (HC), the goal of this study was to examine the possible neuroprotective effect of pioglitazone (PIO) on the electrophysiological alterations of hippocampus, a major area of cognition, in the experimental model of bile duct ligation (BDL). We used adult male Wistar rats in the present study to perform BDL or sham surgery. Pioglitazone was administered in BDL rats two weeks after the surgery for the next continuous four weeks. The effects of pioglitazone on BDL-induced electrophysiological alterations of the CA1 pyramidal neurons in the hippocampus were evaluated by whole-cell patch clamp recordings. Our findings demonstrated that chronic administration of PIO could not reverse the electrophysiological changes in the CA1 pyramidal neurons of the hippocampus in BDL rats but could improve the hepatic dysfunction.Together, the results of this study suggest that PIO administration cannot counteract altered intrinsic properties of the hippocampal neurons which has been shown recently as an involved mechanism of the cognitive impairments in hepatic encephalopathy (HE).

Protective Effect of Metformin, Resveratrol and Alpha-lipoic Acid on Radiation- Induced Pneumonitis and Fibrosis: A Histopathological Study.

BACKGROUND: Radiation-induced pneumonitis and fibrosis are the most common side effects of chest radiotherapy. They result from massive and chronic production of Reactive Oxygen Species (ROS), inhibition of antioxidant enzymes as well as the release of several inflammatory mediators. In this study, we aimed to detect the radioprotective effects of metformin (as inhibitor of mitochondrial ROS), resveratrol (as stimulator of antioxidant defense enzymes) and alpha-lipoic acid (as direct antioxidant) for alleviating radiation-induced pneumonitis and fibrosis. METHODS: 80 Male Mice were randomly allotted to eight groups which include G1: control; G2: resveratrol; G3: alpha-lipoic acid; G4: metformin; G5: radiation; G6: radiation plus resveratrol; G7: radiation plus alpha-lipoic acid; G8: radiation plus metformin. Drugs' doses were as follows: 100 mg/kg metformin, 200 mg/kg resveratrol and 200 mg/kg alpha-lipoic acid. Irradiation with a single radiation dose of 18 Gy was performed using a cobalt-60 (60Co) gamma-ray source. After 80 days, all mice were sacrificed and their lung tissues evaluated for morphological changes using histopathological markers. RESULTS: Irradiation led to acute pneumonitis including infiltration of inflammatory cells and damages to alveolar and vascular, as well as mild fibrosis. Metformin, alpha-lipoic acid and resveratrol were able to reduce pneumonitis and overcome radiation-induced fibrosis. CONCLUSION: All agents could protect against radiation-induced lung injury moderately. It is possible that administering higher doses of these drugs over a long period of time could give better radioprotection of the lung.

Characterization of the CA1 pyramidal neurons in rat model of hepatic cirrhosis: insights into their electrophysiological properties.

Although the key contributors of altering neurological function in hepatic encephalopathy are relatively well known, the electrophysiological mechanism of CA1 damage, a key vulnerable area during hyperammonemia, have not yet been defined. Therefore, here we focus on the electrophysiological mechanisms of cognitive impairments following bile duct ligation (BDL). We performed patch-clamp recordings from the CA1 pyramidal neurons in hippocampus of male Wistar rats, which underwent sham or BDL surgery. A striking electrophysiological change of hippocampal neurons in experimental model of BDL was observed in the present study. Spontaneous firing frequency and rate of action potential (AP) rebound was decreased and afterhyperpolarization amplitude (AHP) was increased significantly in hippocampal cells of BDL animals compared to sham group. Together, the results suggest that altered intrinsic properties of the hippocampal neurons may contribute to the cognitive abnormalities during hepatic encephalopathy (HE), highlighting the electrophysiological mechanisms for providing new treatments against HE.

Nephropathic complication of type-2 diabetes is following pattern of autoimmune diseases?

The impact of several environmental and genetic factors on diabetes and its complications is well documented. The present study was aimed to examine the serum levels of IL-17A and IFN-gamma as antagonistic cytokines in nephropathic and non-nephropathic type-2 diabetic patients. In this experimental study, serum samples were obtained from 180 type-2 diabetic patients, 100 nephropathic type-2 diabetic patients and 100 healthy controls. Serum levels of IL-17A and IFN-gamma was detected by ELISA. Results of this study showed that the serum level of IFN-gamma was higher in both diabetic patients (nephropathic and non-nephropathic) in comparison to the controls. In terms of IL-17A, while non-nephropathic type-2 diabetic patients showed an increased serum level of it, the other patients group had a lower serum level. Based on these findings, it can be concluded that the lower serum level of IL-17A is possibly associated with nephropathic complications of type-2 diabetes.